Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Although immune checkpoint inhibitors have changed the treatment landscape in several tumor types, their clinical benefit in CRC remains largely confined to mismatch repair-deficient disease. Most colorectal cancers are microsatellite-stable and show primary resistance to immunotherapy, highlighting the need to better understand tumor microenvironmental factors that shape immune responsiveness. Increasing evidence suggests that the tumor-associated microbiota contributes to CRC progression and treatment response. Among the implicated taxa, Fusobacterium nucleatum (Fn) is frequently enriched in colorectal tumors and is associated with adverse clinicopathologic features, poor prognosis, and reduced sensitivity to systemic therapies. Recent studies further suggest that Fn-related succinate accumulation may promote myeloid-dominated immune suppression and impaired cytotoxic T-cell activity. In this review, we summarize current evidence linking the Fn-succinate axis to immune regulation in CRC, discuss its relevance to immunotherapy resistance, and highlight key translational challenges.
It is critical that women undertaking medically assisted reproductive (MAR) treatment and their clinicians know whether the treatments are associated with an increased risk of hormone-related cancers. To determine the risk of hormone-related cancers following MAR treatment. This cohort study used an emulated target trial design including Australian health registries and administrative datasets. Participants included women enrolled in Medicare, Australia's universal health insurance scheme, aged 18 to 55 years between January 1, 1991, and December 31, 2018. Data were analyzed from April 2024 to July 2025. Exposures were defined from Medicare records: assisted reproduction therapy, intrauterine insemination or ovarian stimulation, and ovulation induction with clomiphene citrate. Hormone-related invasive cancers (identified in the Australian Cancer Database) included breast, ovarian, uterine, thyroid, colorectal cancers and melanoma; in situ cancers included breast cancer and melanoma. Three cancers with no hormonal links-pancreatic, lung, and hematological-were included as negative controls. Flexible parametric survival models ascertained hazard ratios (HRs) and cumulative marginal survival differences in incident cancers per 100 000 population. E-values assessed the risk of bias due to unmeasured confounding. A total of 1 748 927 women were identified, including 396 661 with history of MAR exposure. Although elevated risk of most hormone-related cancers was observed after MAR treatment (HRs, 1.09-1.64), E-value analysis suggested confounding due to underlying infertility conditions (ie, endometriosis, polycystic ovarian syndrome) could account for this observed elevation for uterine, ovarian, and thyroid cancers. For any specific invasive cancer, fewer than 20 extra cancers per 100 000 women each year were estimated for treated vs comparator groups. Emulated trials on the 6 hormone-related cancers and pancreatic and hematological cancers showed increased cancer risk in the first years after treatment, suggesting detection bias. Increased risk of hematological cancers was observed after MAR treatment (HRs, 1.18-1.27), indicating uncontrolled confounding by race and ethnicity may account for observed excess risk seen for several cancers. Some treatments were associated with decreased lung cancer risk (HRs, 0.72-0.82). In this cohort study of MAR and cancer using a target trial emulation design, although associations between MAR and some hormone-related cancers were observed, the estimated difference in the number of expected cancers was small and may be explained by unmeasured confounding and detection bias.
To develop a large language model (LLM) (Truveta Language Model Oncology [TLM-Oncology]) to extract real-world oncology staging data across multiple cancer types from clinical documentation with high precision. We selected patients from a large integrated health system with a bladder, cervical, colorectal, breast, or prostate cancer diagnosis in their structured data. We identified relevant notes using note metadata and keywords and annotated overall stage; T, N, and M; associated timeframe; and cancer diagnosis on a sample of 700 notes as ground truth. Of the 700 notes, 450 were divided equally between training, validation, and test sets for bladder, cervical, and colorectal cancers; 150 were used for targeted error-pattern training on these cancers; and the remaining 100 were split equally between breast and prostate cancer test sets. We started with a pretrained LLM and applied supervised fine-tuning to adapt the model to structured clinical information extraction. Model performance was measured using precision, recall, and F1 scores at the relation level and individual attribute level. We extracted over 2.5 million staging records for 217,768 patients from over two million notes. Relation-level precision across the six attributes ranged from 0.77 to 1.0 for the first three cancers and, without further training, 0.83 to 1.0 for two additional cancers. TLM-Oncology extracted detailed cancer staging information for five cancers from a variety of clinical documentation within a single integrated health system with high precision and turned data that were previously inaccessible into a valuable resource for downstream use. We are currently evaluating TLM-Oncology on other solid tumors within three additional health systems to assess its generalizability.
In colorectal cancer care, planned surgery is sometimes performed without preoperative histological confirmation of malignancy, raising concerns that diagnostic uncertainty may affect surgical quality. Do surgeons maintain high quality oncological resection practices when colorectal cancer is suspected yet not histologically confirmed? We conducted a nationwide retrospective cohort study using the Danish Colorectal Cancer Group database, including patients undergoing planned colorectal cancer surgery between 2016 and 2020. Patients were grouped according to whether malignancy was histologically confirmed prior to surgery. Surgical quality was assessed by lymph node harvest, resection margins and microradicality. Multivariable regression analyses adjusted for demographic, clinical and surgical factors. Among 12,260 included patients, 16.7% (n = 2053) underwent surgery without preoperative histological confirmation. Despite this, key indicators of oncological resection quality remained consistently high across both groups. Mean lymph node harvest approached 30 in both groups (29.3 vs. 29.6), and resection margins were comparable. Microradical resection was achieved in 91.8% of cases regardless of diagnostic status and although statistical adjustment identified a minor difference in microradicality, this was not considered clinically meaningful (regression coefficient - 0.22; number needed to treat = 63). Nearly one in six colorectal resections in Denmark is performed without definitive preoperative histology. Surgical quality, evaluated using established oncological criteria, did not differ between these two groups. This is likely the result of multidisciplinary assessment and standardized surgical protocols. These findings support the safety of proceeding directly to surgery when multidisciplinary evaluation indicates strong clinical and radiological suspicion of colorectal cancer, potentially avoiding delays and risks associated with repeat diagnostic procedures.
Pediatric colorectal malignancies are rare, with lymphomas- predominantly non- Hodgkin's lymphoma (NHL) representing the most common type, accounting to 0.5-2% of large bowel malignancies. Colorectal NHL can be primary or secondary. This study analyzes the rare manifestations of pediatric colorectal lymphoma and examines their diagnostic challenges and surgical implications. A Pubmed search was done with search words "lymphoma of colon pediatric" with filter of last 5 years on 12 Feb 2026. The search comprised of 47 articles, among which 10 relevant articles were selected. After going through the articles, one article was excluded. 9 articles were finally included in the study. Colorectal lymphoma can be a primary malignancy or it can arise in the background of inflammatory bowel disease. It can also be a secondary extension from bulky intra- abdominal lymphoma. Clinical manifestations can present either as flare up of inflammatory bowel disease or colorectal carcinoma or bowel obstruction or acute abdomen. This can lead to potential diagnostic delay and inappropriate escalation of medical therapy, unless early biopsy is performed. The routine use of broad spectrum anti-infectives in lymphoma decreased the gastrointestinal integrity and increased opportunistic infections in the gut, complicating the clinical assessment. Imaging aids in differentiation from epithelial malignancies. It also guides in staging, treatment and operative planning. Rare presentations of colonic lymphoma were its appearance in a child (below five years) on medical management for ulcerative colitis, and in another patient on Vedolizumab for Crohn's disease. Another rare presentation recorded occurrence of primary rectal lymphoma in an eleven year old child. Early presentation (below 10 years) with synchronous colorectal carcinoma and family history of malignancy, suggested an underlying genetic cancer predisposition syndrome. Surgery plays a crucial role in managing complications like perforation, obstruction and intussusception when lymphoma is the lead point. Laparoscopy assisted en-bloc resection is feasible in selected cases. Pediatric colorectal lymphomas represent a clinically significant and occasionally misleading entity. While systemic chemotherapy remains the cornerstone of treatment, surgical intervention has a defined role in tissue diagnosis and management of complications. Early recognition and coordinated multidisciplinary care are essential to optimize outcomes.
Comprehensive genomic profiling (CGP) is critical for optimal clinical care for gastrointestinal (GI) carcinomas. Outside of biliary tract cancers (BTCs), actionable fusions are uncommon and the utility of routine RNA-based fusion testing in GI cancers is not well established. We therefore evaluated routinely conducted RNA-based fusion testing in GI cancers at a single center. Patients with GI carcinomas who underwent RNA-based tissue fusion testing at Massachusetts General Brigham Cancer Institute were included. Tumors with fusions were characterized for molecular and histopathologic associations. RSPO2/3 fusions in lower GI cancers were further characterized for survival and benefit from targeted therapy. A total of 2,300 patients with GI carcinomas were included; 139 (6.0%) had a detected fusion. BTCs had the highest fusion incidence (13.7%), mostly FGFR2. Fusions were detected in 3.5-7.7% of colorectal cancer (CRC), pancreatic, esophagogastric adenocarcinoma (EGA), and small bowel carcinomas. Fusions of BRAF, FGFR1-3, NTRK1/3, RSPO2/3, and NRG1 were rare (excepting FGFR2 in BTCs) but observed in 3 or more cancer types. RSPO2/3 fusions were the second most frequent overall (1.4%) and most frequent in CRC (2.6%) and small bowel cancers (5.8%). RSPO2/3 fusions were associated with poorly differentiated and mucinous histology, preserved mismatch repair, wild-type (WT) APC, and either KRAS or BRAF V600E mutations, however were not associated with differential survival in CRC patients receiving BRAF targeted therapy. Fifteen of 20 (75%) pancreatic tumors with fusions were KRAS WT; in KRAS-mutated pancreatic cancer, most fusions were of unclear significance. Receipt of fusion targeted therapy was associated with longer survival in fusion positive pancreatic cancers and FGFR2-fusion positive BTCs. 20 fusions detected in EGA were heterogenous, including FGFR, CLDN18, and RSPO2. RNA-based testing identifies potentially actionable fusions in a clinically significant fraction of GI carcinomas. Patients who receive fusion targeted therapy during their clinical course demonstrate longer survival, supporting CGP including fusion testing for all patients. Lower GI cancers harboring RSPO2/3 fusions have a distinct molecular and pathologic phenotype, but demonstrate few clinical differences. Several detected fusions had novel gene partners, highlighting the utility of partner-agnostic fusion testing.
Emerging endoscopic techniques are expanding opportunities for minimally invasive therapy in early colorectal cancers (CRCs). Data regarding the clinicopathological features and outcomes of colon versus rectal cancers in Tis, T1, and T2 stages remain limited. This study evaluates and compares these two entities to clarify their oncologic differences. We retrospectively analyzed patients with pTis-T2 CRCs treated by endoscopic or surgical resection at a single Japanese center between 2001 and 2022. Tumor location was classified as rectum (Ra, Rb) or colon (cecum to RS). Clinical variables (sex and age), pathological features (tumor size, differentiation, lymphatic invasion [Ly], vascular invasion [V], and tumor budding), and recurrence and metastasis rates were compared according to tumor location. The proportion of rectal cancer rose with invasion depth, from 16.2% (271/1673) in Tis to 18.5% (248/1337) in T1 and 26.4% (178/675) in T2 (p < 0.01). Compared with T1 colon cancer, T1 rectal cancer showed higher rates of Ly1-2 (35.1% vs. 27.4%), V1-2 (37.9% vs. 24.6%), and recurrence (4.4% vs. 0.6%) (all p < 0.05). Similarly, T2 rectal cancer showed higher V1-2 (68.5% vs. 54.1%) and recurrence rates (13.5% vs. 5.0%) compared with colon cancer (all p < 0.05). No significant differences were observed in lymph node or distant metastasis at either T1 or T2 stages. Rectal cancers demonstrate more aggressive features and higher recurrence rates than colon cancers. Consequently, these patients require more stringent therapeutic approaches and rigorous postoperative surveillance, even in early stages. Umin Clinical Trials Registry, UMIN 000042622.
BackgroundReturn to work (RTW) is a critical aspect of recovery and social reintegration for cancer survivors. With increasing survival rates, understanding the research landscape in this field has become essential.ObjectiveThis study aims to systematically identify research hotspots, emerging trends, and development directions in the field of return to work among cancer patients through bibliometric analysis.MethodsRelevant literature published between January 1, 2004, and May 31, 2024, was retrieved from the Web of Science （WoS） Core Collection. Bibliometric analysis and knowledge mapping were performed using CiteSpace for visualization.ResultsA total of 1370 relevant publications were retrieved, with 767 English articles included in the visualization analysis after screening. These publications originated from 54 countries, with more than 30 articles from 10 countries or regions. The top three countries in terms of publication volume were the Netherlands, the United States, and Australia. The leading institutions were the University of Amsterdam, Vrije Universiteit Amsterdam, and Academic Medical Center Amsterdam. The most prolific author was Frings-Dresen, M.H.W. The top five keywords were "Return to work," "Breast cancer," "Survivors," "Quality of life," and "Employment." Keyword cluster analysis revealed 15 clusters, divided into four major categories: Population and Disease Types (cancer survivorship, cancer patients, head and neck cancer, colorectal cancer, breast cancer survivors), Health Promotion and Work Ability (return to work, work ability, health promotion, functional outcome), Health Economics and Injury Compensation (supervisor, health economics, disability pension, sick leave), and Research Types (scoping review). An emergent analysis of keywords indicates a shift from early terms like "quality of life," "rehabilitation," and "sick leave" to "needs," "burden," "impairment," and "management."ConclusionBreast cancer is the most common focus within studies on cancer patients returning to work, with colorectal and head and neck cancers gaining attention. Research is increasingly focused on the economic burden's impact on cancer survivors. Effective interventions could include employer-level initiatives, vocational counseling, patient education, psychological support, and multidisciplinary measures combining biofeedback-assisted behavioral training or physical exercise.
Drug resistance and toxicity are major challenges for colorectal cancer (CRC) therapy. Kaempferol (KMP), a natural flavonoid compound, is characterized by low toxicity and multi-targeted effects. KMP has multiple biological functions (anti-inflammation, antioxidation, anti-angiogenesis, apoptosis induction, and immunoregulation). Therefore, KMP is extensively investigated the treatment of various diseases, including cancer. Currently, a series of studies has explored the potential anti-cancer role in CRC therapy. KMP can inhibit the progression of colitis to CRC. Furthermore, KMP suppresses the proliferation of CRC cells and tumor growth. The mechanisms regulated by KMP are involved in multiple signaling pathways such as the matrix metalloproteinases family, VEGF/VEGFR, Wnt/β-catenin, and PI3K/Akt/mTOR. As a multi-targeted inhibitor, KMP shows its natural advantage in combination therapy and is often defined as a sensitizer or attenuator. However, due to the poor stability, absorption, and bioavailability of KMP, its clinical value is hindered. Nano-based delivery systems can compensate for these shortcomings and boost their therapeutic potential. KMP is a hopeful anticancer flavonol, and this review aims to summarize its anticancer effects, mechanisms, and potential applications in CRC.
Examine which demographic, lifestyle, and clinical risk factors differ between patients with early-onset colorectal cancers (EOCRC) compared to late-onset colorectal cancers (LOCRC). We conducted a case-case comparison of risk factors and symptoms for EOCRC and LOCRC, utilizing the Ohio Colorectal Cancer Prevention Initiative (OCCPI) data, a statewide study of newly diagnosed CRC among Ohio residents, aged 20-92 years. Unconditional logistic regression (odds ratios (OR) and 95% confidence intervals (CI)) was used to compare risk factors by age-at-diagnoses; those diagnosed < 50 years (EOCRC, N = 288) compared to those diagnosed ≥ 50 years (LOCRC, N = 1,018), adjusting for sex, race/ethnicity, education, smoking status, and family history of CRC. Compared to LOCRC, EOCRC cases had higher odds of ever consuming alcohol (OR = 2.47, CI: 1.55-3.91), consuming more alcohol in their teens/twenties than in other decades (OR = 1.85, CI: 1.36-2.51), and binge drinking (OR = 3.15, CI: 2.31-4.30). EOCRC cases were more likely to have Lynch syndrome (OR = 4.61, CI: 2.72-7.84), and report experiencing pre-diagnostic CRC symptoms (OR = 6.08, CI: 3.77-9.82), including blood in stool (52.3 vs. 30.7%), change in bowel habits (37.2 vs. 19.8%), and bowel obstruction (13.9 vs. 7.7%). Birth weight, inflammatory bowel disease, irritable bowel syndrome, and sex did not differ by age-at-diagnosis. However, when birthweight was compared between the youngest EOCRC to the oldest LOCRC cases (< 40 vs. ≥ 65 years), odds of birthweight of < 6lbs was higher in the youngest cases (OR: 2.15, CI: 0.95-4.87). Alcohol consumption, consuming the most alcohol in one's teens/twenties, binge drinking, having Lynch syndrome, and pre-diagnostic CRC symptoms were more associated with EOCRC than LOCRC.
Colorectal cancer (CRC) is a leading global malignancy, with approximately 1.9 million new cases and over 900,000 deaths recorded in 2022, yet evidence-based integrative oncology strategies remain inconsistently incorporated into routine care. This narrative review synthesizes current evidence across the full CRC care continuum, from primary prevention through long-term survivorship. High-fiber diets, Mediterranean dietary patterns, calcium supplementation, regular physical activity, healthy weight maintenance, and berberine each demonstrate reproducible CRC risk reduction in large prospective cohorts and multicenter randomized controlled trials. The CHALLENGE trial (NEJM 2025) provides the first randomized phase 3 evidence that structured exercise after adjuvant chemotherapy reduces disease recurrence (HR 0.72) and death (HR 0.63) in colon cancer. Aspirin chemoprevention requires individualized risk-benefit assessment per 2022 US Preventive Services Task Force guidelines; preliminary CaPP3 trial data (conference presentation, June 2025; not yet peer-reviewed) suggest non-inferiority of low-dose aspirin (75-100 mg/day) to 600 mg/day in Lynch syndrome, pending formal publication. Fusobacterium nucleatum promotes colorectal carcinogenesis through five mechanistically distinct pathways: FadA-mediated Wnt/β-catenin activation, Fap2- and CbpF-mediated immune evasion via TIGIT and CEACAM1, succinate-HIF-1α-EZH2-mediated immune suppression, Hippo pathway-mediated suppression of pyroptosis, and autophagy-induced chemoresistance. Perioperative multi-strain probiotics significantly reduce postoperative infectious complications, and fecal microbiota transplantation shows preliminary promise for sensitizing microsatellite-stable CRC to immunotherapy. The 2022-2024 SIO-ASCO and ASCO-SIO clinical practice guidelines endorse mindfulness-based interventions, yoga, and acupuncture for anxiety, depression, fatigue, and cancer-related pain. Systematic integration of these interventions into multidisciplinary CRC care requires standardized implementation frameworks, CRC-specific clinical trials for mind-body modalities, and bioavailability-optimized phytochemical formulations.
Lynch syndrome (LS) is an autosomal dominant cancer predisposition syndrome, associated with substantially increased risks of colorectal and gynecologic malignancies. Endometrial cancer may serve as a sentinel cancer for LS, placing gynecologists and gynecologic oncologists in a key position for early recognition and long-term management. This joint statement was developed through a multidisciplinary process involving the Japan Society of Gynecologic Oncology, the Japan Society of Clinical Oncology, the Japanese Society of Hereditary Tumors, and the Japanese Society for Cancer of the Colon and Rectum. It aims to clarify the clinical utility of diagnosing LS in gynecologic oncology within the Japanese healthcare system. We outline a tumor-first paradigm in which universal mismatch repair immunohistochemistry and/or microsatellite instability testing for endometrial cancer facilitates LS detection and provides actionable biomarkers for systemic therapy. This statement summarizes the clinical impact of LS diagnosis across gynecologic oncology. We highlight patterns of synchronous and metachronous malignancies and the prevalence of LS in ovarian cancer, particularly in endometrioid and clear-cell subtypes. We discuss surgical implications, including risk-reducing hysterectomy with bilateral salpingo-oophorectomy, consideration of concomitant gynecologic risk-reducing surgery during colorectal cancer resection, and individualized ovarian preservation in selected early-stage endometrial cancer or atypical endometrial hyperplasia. We also review the treatment relevance of deficient mismatch repair/microsatellite instability-high status for immune checkpoint inhibitors and emerging fertility-preserving approaches, and address surveillance, cascade testing for relatives, implementation barriers, and the need for multidisciplinary pathways and healthcare system-level support to ensure equitable access to genetic counseling and testing.
Several studies have investigated colorectal neoplasia (CRN) in Vietnamese patients who present with lower gastrointestinal symptoms. However, data on subjects without symptoms is limited. This study aimed to determine the prevalence and risk factors for CRN in asymptomatic Vietnamese adults. This was a prospective, cross-sectional, single-center study. Participants were consecutively recruited from asymptomatic individuals who were self-selected to undergo self-funded screening colonoscopy. CRN was defined as the presence of adenoma, sessile serrated lesions, or colorectal cancer. Advanced CRN included adenoma ≥ 1 cm, with villous features or high-grade dysplasia; sessile serrated lesion ≥ 1 cm or with dysplasia; traditional serrated adenoma; or colorectal cancer. Multivariable logistic regression was performed to identify independent risk factors for CRN, adjusting for age, sex, BMI, family history of colorectal cancer, smoking status, and alcohol consumption. There were 714 patients, with a median age of 51 (18-79 years) and a female-to-male ratio of 1:1.46. In this screening-attending cohort, the prevalence of overall CRN and advanced CRN were 26.2% and 9.0%, respectively. In the multivariate analysis, factors significantly associated with CRN included increasing age per 10-year increment (odds ratio [OR]: 1.76; 95% confidence interval [CI]: 1.47-2.11; p < 0.001), body mass index ≥ 23 kg/m2 (OR: 1.70; 95% CI: 1.16-2.50; p = 0.006), alcohol consumption (OR: 1.83, 95% CI: 1.10-3.04, p = 0.020), and family history of colorectal cancer (OR: 2.43; 95% CI: 1.36-4.37; p = 0.003). CRN was prevalent in this self-selected screening-attending cohort in a private clinical setting. Increasing age, overweight, and family history of colorectal cancer were independent factors associated with CRN.
Accurate segmentation of colorectal polyps is crucial for the early prevention and diagnosis of colorectal cancer. However, due to the high heterogeneity of polyps in terms of shape, size, and texture, as well as the complexity of the intestinal environment (such as folds, specular reflections, and fecal residues), existing methods still face significant challenges in boundary localization and small-polyp detection. To address these issues, this paper proposes a Polyp Segmentation Network based on Pinwheel Convolution and Dual Attention (PWD-Net). The proposed network adopts a U-shaped encoder-decoder architecture, where a pretrained ResNet is employed as the encoder to extract multi-level local features. Specifically, a Pinwheel Convolution Module (PCM) is introduced at the bottleneck layer to capture the global geometric structure and multi-directional contextual information of polyps through multi-angle rotated convolution kernels. A Dual-Attention Mechanism (DAM) that integrates channel attention and spatial attention is designed to adaptively suppress background noise and enhance polyp-region features. In addition, a Multi-scale Feature Fusion (MSF) strategy is employed to combine deep semantic information with shallow boundary details, ensuring both completeness and precision of segmentation results. Experiments conducted on the Kvasir-SEG and CVC-ClinicDB datasets demonstrate that PWD-Net achieves average Dice coefficients of 0.865 and 0.944, and IoU scores of 0.765 and 0.892, respectively, significantly outperforming existing state-of-the-art methods. Ablation studies verify the effectiveness of each module, and cross-dataset evaluations confirm the strong generalization ability of the model. This study provides a high-precision and robust solution for clinical polyp segmentation, offering significant value for the early diagnosis of colorectal precancerous lesions and supporting computer-aided intervention.
Extensive epidemiological and mechanistic studies have established links between specific infections and cancer, but the inherited host-genetic contribution to broader infection-cancer relationships remains incompletely characterized. Here, we integrated genome-wide association study summary statistics for multiple infectious diseases and cancers from European- and East Asian-ancestry populations and evaluated shared host genetic architecture across genome-wide and local genetic sharing, tissue- and cell-type enrichment, cross-trait locus discovery, functional gene prioritization, proteome-level integration and exploratory bidirectional Mendelian randomization. In the European ancestry analyses, four complementary genome-wide approaches identified 11, 21, 44 and 11 significant infection-cancer trait pairs, respectively; 11 pairs were supported by at least three approaches, and sepsis-lung cancer, pneumonia-kidney cancer and sepsis-colorectal cancer were supported by all four. In the East Asian-ancestry analyses, tuberculosis-lung cancer showed the most prominent regional shared genetic architecture. Local analyses further showed that genetic overlap was not uniformly distributed across the genome, but was concentrated in specific regions with heterogeneous directions of effect. Tissue- and cell-type enrichment analyses indicated that shared signals were primarily concentrated in mucosal and epithelial barrier-related tissues and immune-cell compartments. Cross-trait analyses identified 396 potential pleiotropic independent risk loci, 14 colocalized variants, and 86 high-confidence pleiotropic genes, while proteome-level analysis identified 83 pleiotropic proteins, including MORF4L1, which was associated with five trait pairs. Exploratory Mendelian randomization provided directional genetic-liability evidence, with the strongest European-ancestry signal linking lung cancer liability to sepsis. Together, these findings support a shared host-genetic component underlying part of the relationship between infections and cancers, involving immune regulation, barrier homeostasis and cellular stress adaptation.
To compare CD4+ T cell, CD8+ T cell infiltration and PD-L1 expression between paired biopsy and resection specimens in gastric and colorectal adenocarcinoma, and evaluate their clinical significance. Paired biopsy and resection specimens from 38 gastric and 40 colorectal adenocarcinoma patients were assessed by immunohistochemistry for CD4+ T cell, CD8+ T cell density and PD-L1 expression. Correlations with clinicopathological parameters and tumor markers were analyzed. In gastric adenocarcinoma, resection specimens showed significantly higher CD4+ T cell, CD8+ T cell density and PD-L1 expression than biopsies (all P<0.05), with CD4+ T cells positively correlated with CA19-9 (R = 0.523, P = 0.026). In colorectal adenocarcinoma, CD8+ T cell density was higher in resection specimens (P = 0.0353); CD4+ T cells negatively correlated with Ki-67 (R=-0.370, P = 0.019), and CD4+/CD8+ ratio negatively correlated with mismatch repair protein expression (R=-0.342, P = 0.029). In both cancers, CD4+/CD8+ ratios at tumor center and invasive margin were positively correlated (gastric: R = 0.5683, P = 0.0002; colorectal: R = 0.7324, P<0.0001). Preoperative neutrophil-to-lymphocyte ratio positively correlated with tumor diameter in both cancers (gastric: R = 0.449, P = 0.011; colorectal: R = 0.631, P = 0.001). CD4+ T cell density differed significantly between cancer types (P <0.0001). ROC analysis demonstrated limited predictive value of biopsy specimens for surgical findings, particularly in colorectal cancer (AUC 0.5-0.7). Biopsy specimens inadequately represent the immune microenvironment of resection specimens, especially in gastric adenocarcinoma. Tumor-type-specific immune assessment of biopsies is essential for guiding precise immunotherapy decisions.
Sporadic synchronous multiple primary colorectal cancer (SSCRC) is uncommon, and its molecular features remain unclear. This study aimed to compare the clinicopathological and molecular characteristics of SSCRC with solitary colorectal cancer and to evaluate microsatellite instability (MSI) status across synchronous lesions. We retrospectively enrolled 46 patients with synchronous CRCs and 202 patients with solitary CRCs. MSI status was determined for each SSCRC lesion using polymerase chain reaction (PCR)-based testing. Additional clinicopathological variables and selected molecular features were also assessed. Compared with solitary CRC, SSCRC index lesions were associated with more advanced clinicopathological features (all P<0.05). The proportion of deficient mismatch repair (dMMR) was significantly higher in SSCRC (19.6% vs. 5.0%, P=0.003). Overall survival was significantly worse in SSCRC (P=0.03), while disease-free survival did not differ significantly between groups. All SSCRC cases demonstrated concordant MSI status across lesions, with 19.6% classified as MSI-H and 80.4% as MSI-L/MSS. MSI status appears central to SSCRC biology and may aid prognostic stratification. SSCRC exhibits distinct clinicopathological and molecular characteristics relative to solitary CRC, supporting the need for lesion-level molecular evaluation to inform personalized management. In particular, patients with dMMR tumors may benefit from immunotherapy, highlighting the clinical importance of MSI assessment.
C-CAT lacks patient-level data on Japanese Society of Medical Oncology (JSMO) specialist involvement. We assessed facility-level registry-listed JSMO specialist availability and C-CAT-reconstructable treatment-process and endpoint-ascertainment measures in colorectal cancer. This nationwide retrospective C-CAT facility-level analysis included 11,906 patients at 261 facilities. The primary exposure was facility-level JSMO specialist count (0-3 vs 4 +); the secondary exposure was gastrointestinal-domain JSMO specialist presence. The primary endpoint was time from systemic therapy start to recorded second-line treatment end. Facility-cluster robust Cox models were used. Endpoint ascertainment, missingness-focused sensitivity analyses, and overall survival (OS) were supportive/contextual. Overall, 5349 patients at 181 facilities were in the 0-3 group and 6557 patients at 80 facilities in the 4 + group. Median time to recorded second-line treatment end was 20.2 versus 23.1 months (log-rank p < 0.001). In facility-cluster robust Cox models, the unadjusted HR for 4 + versus 0-3 specialists was 0.840 (95% CI 0.761-0.927; p < 0.001), attenuating after facility-category adjustment (HR, 0.948; 95% CI 0.853-1.055; p = 0.329) and clinical adjustment (HR, 0.968; 95% CI 0.866-1.082; p = 0.565). Second-line end-date availability was lower in the 4 + group (61.6% vs 69.1%). Supportive OS showed no specialist-associated survival advantage (median, 50.2 vs 51.3 months; clinically adjusted HR, 0.962; 95% CI 0.816-1.135; p = 0.648). C-CAT can reconstruct facility-level treatment-process and endpoint-ascertainment measures, but current C-CAT data do not support specialist-attributable clinical interpretation. Direct evaluation requires chemotherapy-specific national database elements.
Inflammation and immuno-nutritional status are key determinants of tumor progression and therapeutic resistance in metastatic colorectal cancer (mCRC). This study aimed to assess the prognostic performance of composite biomarker global inflammatory-nutritional index (GINI), which integrates multiple inflammatory, immune, and nutritional parameters, for predicting time to next treatment (TTNT) and overall survival (OS) in real-world mCRC patients receiving third-line therapy. A comprehensive analysis was performed on 320 mCRC patients hospitalized at Shanghai Municipal Hospital of Traditional Chinese Medicine. Demographic data, vital signs, laboratory results, and diagnostic information were collected. Clinical characteristics were compared across GINI tertiles high GINI group (H group), moderate GINI group (M group), and low GINI group (L group). Kaplan-Meier survival analysis, Cox proportional hazards regression, time-dependent receiver operating characteristic (ROC) analysis, and restricted cubic spline (RCS) modeling were applied to systematically characterize the association between GINI and mortality, with subgroup analyses conducted accordingly. Significant differences were identified in 1-, 3-, and 5-year mortality rates across the three groups (P<0.05). Cox proportional hazards modeling indicated that GINI was a significant predictor of OS, with a statistically significant survival difference between the H and L groups (P<0.05). RCS modeling demonstrated a significant linear association between GINI and OS (POverall<0.01, PNonlinear≥0.05), and time-dependent ROC analysis showed favorable predictive performance at multiple follow-up time points. For TTNT following third-line therapy, significant differences were also observed among groups (P<0.05). Cox proportional hazards analysis showed that TTNT was significantly shorter in the H group than in the M and L groups (P<0.05). A nonlinear association was observed between GINI and TTNT following third-line therapy (POverall<0.05, PNonlinear<0.05), with better predictive performance at 6, 12, and 18 months. Subgroup analyses further demonstrated significant associations between clinical characteristics, including non-obese status and metastatic site, and prognostic outcomes, particularly supporting the relationship between GINI and TTNT following third-line therapy in patients with lung and bone metastases. GINI is significantly associated with overall mortality risk and TTNT following third-line therapy in mCRC and may serve as a clinically informative indicator for prognostic assessment.
Colorectal cancer (CRC) is a substantial global health challenge due to high mortality rates. This study focused on constructing and validating a calcium metabolism-related genes (CAMRGs) signature for CRC outcome prediction. Transcriptomic and clinical data for CRC were integrated from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A prognostic risk model was constructed using least absolute shrinkage and selection operator (LASSO)-Cox regression analysis. The predictive performance of the model was validated using an external dataset (GSE17536). Furthermore, the expression levels of the identified prognostic genes were preliminarily assessed via reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in clinical specimens. PRKCB, ATP2A3, PLCB4, and SLC25A6 were detected as prognostic genes and used to develop risk models. The risk model differentiated samples into high- and low-risk groups with notable variations in overall survival (OS) (P<0.0001), demonstrating favorable predictive performance [area under the curve (AUC) >0.6]. Gene set enrichment analysis (GSEA) reflected marked enrichment of pathways related to metabolism and immune signaling (e.g., oxidative phosphorylation and chemokine signaling) between the two groups (P<0.05). Risk score, age, and pathological stage were defined as independent prognostic factors and the nomogram demonstrated strong predictive performance (AUC >0.8). Finally, RT-qPCR expression assessed the significantly lower expression of PRKCB and ATP2A3 and higher expression of PLCB4 in CRC patients compared to controls (P<0.05). A CAMRG signature was developed and preliminary examination of CRC prognosis prediction. This model might assist in risk assessment and inform individualized treatment strategies.