Most squamous cell carcinomas of the anus, or anal cancers, are attributable to persistent infection with the human papillomavirus (HPV), analogous to cervical cancer. Although rare in the general population, rates of anal cancer are high among people with immune-compromising conditions or a history of HPV-related cancers. Recent evidence demonstrates that treatment of high-grade squamous intraepithelial lesions (HSIL), a precursor of anal cancer, prevents progression to anal cancer. This has motivated the international release of several guideline statements now recommending anal cancer screening. For a new practice of cancer screening to be integrated into routine care for at-risk populations, implementation strategies will need adaptation for local settings. Our aim is to illustrate the potential value of combining the methods of implementation science with the anal screening cascade framework to support evidence-informed adoption of the guidelines across the different clinical services points where patients might undergo anal cancer screening. We point out means by which research activity could be directed, with particular attention to identifying and addressing care gaps to inform the adoption and scale-up of anal cancer screening. These approaches may help to guide local decisions regarding first steps for anal cancer screening implementation, including determining which populations may need enhanced effort, and to identify where more preparation may be needed. It is time to understand how to best implement anal cancer screening. Although rare in the general population, rates of anal cancer are 20 to 100 times higher among people living with HIV, or with solid organ transplants, or among women who have had human papillomavirus-related cancers. Like cervical and colorectal cancer, early detection and treatment can prevent anal cancer. Unlike cervical or colorectal cancer, most jurisdictions do not routinely screen for anal cancer. In 2024, the first international guidelines for anal cancer screening were released. They recommend that clinicians offer screening to people at the highest risk—those who are at greater than 10 times the risk of the general population. In our paper, we describe strategies to evaluate early attempts at anal cancer screening implementation to support efforts to ensure that anal cancer screening becomes part of regular health care for people in whom it is recommended.
This consensus by the CSCO Pancreatic Cancer Expert Committee establishes evidence-based guidelines for molecular testing in pancreatic ductal adenocarcinoma. It details recommendations for biomarkers (e.g., KRAS, BRCA, MSI), liquid biopsy, and precision imaging to direct targeted therapies and immunotherapy, aiming to standardize diagnosis and optimize individualized patient care. Pancreatic ductal adenocarcinoma (PDAC) is the most common pathological type of primary pancreatic malignancy, accounting for ~95% of cases and generally referred to as pancreatic cancer [1]. Its prognosis is extremely poor and its incidence continues to rise [2]. According to the most recent global cancer statistics, the incidence of pancreatic cancer ranks 12th among all cancers, and its mortality ranks 6th, making it one of the deadliest malignancies worldwide [3]. Approximately 57% of patients have metastatic disease at diagnosis and require systemic therapy, for which chemotherapy remains the standard first-line option [1]. However, the overall response rate to currently available systemic regimens is low, and the 5-year survival rate for patients with metastatic disease remains below 5% [3]. Although most pancreatic cancers harbor canonical driver mutations, they exhibit marked heterogeneity at the molecular level. Whole-genome sequencing (WGS) and integrative genomic analyses have identified molecular subtypes of PDAC with potential clinical relevance [4-9]. With the increasing implementation of precision oncology, the Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Pancreatic Cancer give a level 1 recommendation to perform genetic and other molecular testing on tissue or cytologic specimens as part of the pathological diagnostic work-up, in order to guide individualized treatment, including targeted therapy and immunotherapy [10]. To further promote the use of genetic and molecular testing in the precision treatment of pancreatic cancer, the CSCO Pancreatic Cancer Expert Committee convened a multidisciplinary panel to develop the present Chinese Expert Consensus on Precision Testing and Molecular Diagnosis of Pancreatic Cancer (2025), aiming to provide clinicians with an authoritative reference for precision diagnostics and treatment decision-making.
Cancer of Unknown Primary (CUP) is an aggressive malignancy with poor patient outcomes. For most patients, the primary site remains elusive, limiting therapeutic options to non-specific chemotherapy. The CUP-COMP study (NCT04750109) assessed the feasibility of integrating molecular profiling with a National Molecular Tumour Board (MTB) into the treatment pathway of patients with CUP. Patients with histologically confirmed CUP were recruited from seven UK sites. Blood- and/or tissue-based molecular profiling was performed with results interpreted via an MTB identifying potentially actionable alterations (PAA). Retrospective tissue and blood alteration analysis assessed concordance and utility. 113/117 patients recruited between June 2021 and February 2023 completed 12 months of follow-up. Of 115 patients with successful molecular profiling, blood-based profiling was more successful (93%) than tissue-based (61%). The MTB identified PAAs in 63% (73/115), with 26% (31/117) treated using a precision medicine (PM) approach. Primary tumours were subsequently confirmed/suspected in 41 patients. Median overall survival (OS) was 9.5 months. Detecting a PAA in blood was impacted by tumour fraction (33% of patients had a tumour fraction <1%). CUP-COMP demonstrates liquid biopsies are highly feasible in CUP. While tissue profiling remains preferable, blood-based profiling offers a timely viable alternative to tissue, especially in selected patients.
The National Institute for Health and Care Excellence (NICE) recommends that women at above-population-level risk of breast cancer (BC) are offered enhanced screening and risk-reducing interventions. Identification of these women largely relies on referral through primary care based on family history criteria. We compared the performance of the NICE criteria with versions of the BOADICEA multifactorial risk model in identifying women who developed BC within 10 years. Analyses included 1258 women aged under 50 years with family history, reproductive, lifestyle and polygenic risk data recruited to the Generations Study between 2004 and 2011 (392 BC cases), weighted to represent the UK population with respect to age and family history of BC. NICE criteria identified 4.4% of women who developed BC within 10 years amongst 1.4% of women who met referral criteria. The full BOADICEA model identified up to 35% of women who developed BC, but with lower specificity and 26.5% of women meeting referral criteria. NICE family history-based criteria applied to women under 50 miss most BCs occurring within 10 years. Multifactorial risk assessment in primary care could substantially improve the identification of women at risk who could be offered interventions before being invited to population-based screening.
In RAS-mutant tumours, ERK phosphorylates the mitochondrial fission GTPase DRP1 to promote mitochondrial fission. DRP1 activity is tumour-promoting in pancreatic and other RAS-driven cancers, but its role in therapeutic resistance is unknown. We developed a panel of patient-derived pancreatic cancer cell lines resistant to the MEK inhibitor trametinib. We used immunofluorescence imaging, in vitro growth assays and orthotopic xenografts to determine the role of DRP1 in trametinib resistance. We find that trametinib-resistant cells exhibit increased expression and phosphorylation of DRP1 compared to sensitive counterparts. Quantitative analysis of mitochondrial structure reveals that mitochondria in resistant cells are morphologically distinct and relatively smaller than sensitive cells treated with trametinib. Genetic and pharmacological inhibition of both c-Myc and CDK6 are sufficient to block DRP1 phosphorylation in resistant cells, suggesting that activation of a c-Myc-CDK6 signalling axis drives reactivation of mitochondrial fission in the absence of MAPK signalling. Importantly, deletion of DRP1 leads to either growth inhibition or re-sensitisation to trametinib in resistant lines. These findings suggest DRP1 contributes to drug resistance, and that inhibition of mitochondrial fission might be a promising therapeutic strategy to combat resistance to MAPK and RAS inhibitors.
Prostate cancer is a leading cause of male cancer-related deaths over the age of 50. New treatment options are urgently needed, especially for prostate tumours that have spread to bone. Targeting aberrant sialylation holds substantial potential for the development of new therapeutics but is relatively unexplored in the context of prostate cancer. Here, using high-affinity Siglec-based sialoglycan-binding reagents (HYDRA) for immunohistochemistry, we quantify tumour sialoglycans in tissues representing the full clinical heterogeneity of prostate cancer. Using immunofluorescence, we profile Siglec receptors in prostate tumours, and using syngeneic mouse models, we evaluate an engineered dual-action sialidase (E-612) as a treatment for prostate cancer bone metastasis. We find that sialoglycans that can engage Siglec-3 (CD33), Siglec-7 and Siglec-9 are upregulated in bone metastatic prostate cancer and show that sialoglycan ligands for Siglec-7 and -9 correlate with poorer patient prognosis. Furthermore, we reveal Siglec receptors and Siglec ligands are co-expressed by immune cells in prostate-derived tumours growing in bone. Indicating the Siglec-sialoglycan axis is clinically actionable in prostate cancer, we show systemic therapy with E-612 can suppress the growth of tumours, increase immune cell infiltration and prolong survival times of mice with bone metastasis. Our findings identify a novel mechanism involving Siglec-engaging sialoglycans in driving the growth of prostate cancer bone metastasis and demonstrate that targeting this axis using an engineered sialidase can impede lethal prostate cancer progression.
Long non-coding RNAs (lncRNAs) regulate gene expression, chromatin organization, and cellular signaling. Although traditionally considered non-coding, 21% of the ~190,000 annotated lncRNA transcripts contain poorly characterized open reading frames with unknown function. We systematically identified lncRNAs encoding micropeptides (MPs) using integrated computational and experimental evidence. Expression profiles across 17 cancer types from The Cancer Genome Atlas (TCGA) were analyzed to identify cancer-associated and transitional lncRNAs (Tr-lncRNAs). Structural modeling using AlphaFold was further applied to predict folding. We identified 478 lncRNA genes encoding 1782 MPs (10-100 amino acids). These MPs exhibit distinct amino acid and dipeptide compositions and are enriched for specific 4-mer motifs compared with canonical proteins. A subset of lncRNAs, including TNN-AS1, PVT1, XIST, and SNHG family members, encode multiple MPs. Analysis across cancer stages identified 2399 Tr-lncRNAs, most of them were cancer type and stage specific. Among these, 314 highly confident MPs from 72 Tr-lncRNAs were further analyzed. Pan-cancer analysis suggested MP-like functions for Tr-lncRNAs such as LINC01234, HAND2-AS1, XIST, UCA1, and HOXA11-AS. While most MPs are predicted to be intrinsically disordered, 3D structural modeling revealed several MPs with stable folds, including ubiquitin-like and RNase H-like structures. Tr-lncRNA-derived MPs represent a previously underexplored class of potentially functional molecules associated with cancer clinical annotation and may serve as biomarkers for disease progression.
Smokers are eligible for lung cancer screening using low dose CT (LDCT) if they have a sufficiently high risk of lung cancer. In England, for example, people are eligible if their estimated risk using either of two validated models (PLCOm2012 and Liverpool Lung Project) exceeds a certain threshold. Risk is often estimated using only cigarette consumption (duration and number per day), yet many smokers also use other cancer-causing tobacco products. SUMMIT is a prospective cohort study of a LDCT screening service. We evaluated the impact of cigars, pipes, and cigarillos on lung cancer risk. Among 13,000 participants who were current/former cigarette smokers, 511 (1 in 25) were also regular users of cigars, pipes, or cigarillos. The 5-year cumulative lung cancer incidence in people who currently smoked both types of tobacco products was 8.85%, versus 5.74% for cigarette only current smokers. Among these 511 participants, the percentage whose risk was below the screening eligibility threshold ignoring other tobacco products which then exceeded the threshold including these products was 0.6% using LLPv2, and 8.2% using PLCOm2012. All tobacco consumption should be considered when determining screening eligibility to avoid missing those who can benefit from LDCT. Clinicaltrials.gov no: NCT03934866.
Gastrointestinal (GI) cancers account for one fifth of all cancer cases and one third of all cancer related deaths worldwide. Despite this, the number of systemic treatment options for these cancers remains overall low compared to other cancer types. Antibody-drug conjugates (ADCs), which are composed of a cytotoxic payload attached to an antibody via a linker, have emerged as a promising class of drugs for cancer therapy over the last decade, leading to several approvals in solid tumours and haematological malignancies. However, their development has been delayed in GI cancers compared to other frequent cancers. Encouraging clinical activity has been recently reported with ADCs targeting Claudin 18.2, CEACAM5 and MET. Switching from tubulin inhibitor payloads to topoisomerase I inhibitor payloads in the last generation of ADCs seems to increase the overall activity in GI cancers, particularly in adenocarcinomas. This is notably evident for MET and CEACAM5, but seems also true for ADCs targeting other broadly prevalent targets. In this article we review the current landscape of ADCs development in GI cancers, highlight potential development hurdles and discuss emerging solutions to bring this new therapeutic modality to its full potential in GI oncology.
Characterising somatic mutation profiles in human breast cancer (HBC) is essential for understanding tumour progression and guiding therapeutic strategies. We performed genomic and transcriptomic analyses to profile the mutational landscape of HBC. In addition to our primary analysis of HBC, we conducted comparative genomic analyses to evaluate the extent to which these mutational processes are recapitulated in canine mammary tumour (CMT), a widely proposed translational model. APOBEC3 (A3)-associated mutations were extensive in HBC but largely absent in CMT, likely due to structural differences in A3 proteins and lower basal expression. Transcriptomic stratification of HBC by A3 activity uncovered that tumours with A3 activity showed a strong association with the PAM50-HER2-Enriched (HER2E) subtype, and FGFR4 was significantly correlated with the expression and enzymatic function of APOBEC3A/B. These findings demonstrate that CMT is an unsuitable model for A3-mediated mutagenesis, emphasising the need to consider the limitations of cross-species mutational modelling in comparative oncology. Moreover, this study identifies a potential regulatory association between FGFR4 and A3, offering insights into the underlying mechanisms of A3-driven mutagenesis and suggesting that the FGFR4-A3 activity could be considered alongside other molecular biomarkers for the classification of the HER2E subtype.
The health consequences of being underweight are less well-studied than obesity. We aimed to examine the association between body mass index (BMI) and mortality from a wide range of diseases across the full BMI spectrum, with particular focus on how low BMI may affect premature and nonpremature death. After excluding ever-smokers and those with pre-existing major diseases, this study included 262 704 women aged 30-79 from the China Kadoorie Biobank. The baseline BMI (kg/m2) was calculated using measured height and weight and classified into six groups: < 18.5, 18.5-19.9, 20.0-22.4, 22.5-23.9 (reference), 24.0-27.9 and ≥ 28.0. Long-term follow-up was conducted by linking to the local death registry. Cox regression was used to estimate the hazard ratios (HRs) of BMI with all-cause and cause-specific mortality, after adjusting for waist circumference and potential confounders. At baseline, 3.9%, 7.8% and 11.4% of participants had BMIs (kg/m2) of < 18.5, 18.5-19.9 and ≥ 28.0, respectively. During a median follow-up of 17.1 years, 29 531 deaths were recorded, including 11 455 premature deaths (under the age of 70) and 18 076 nonpremature deaths. The risk of all-cause mortality significantly increased at the lower extreme of BMI, reached a nadir around 23.5 kg/m2 estimated from restricted cubic splines and showed a modest increase at the upper extreme. Participants with BMI < 18.5, 18.5-19.9 and 20.0-22.4 had higher risks of premature death (HRs) of 1.91 (1.73-2.10), 1.24 (1.14-1.34) and 1.16 (1.11-1.21), respectively. The corresponding HRs for nonpremature death were 1.46 (1.36-1.56), 1.17 (1.10-1.23) and 1.04 (1.01-1.08). The analysis of premature death involved 33 diseases from eight ICD-10 chapters, and nonpremature death involved 40 diseases from nine chapters. Underweight was linked to an increased risk of premature death in seven chapters and 10 diseases, including neoplasms (HR = 1.36, 95% CI: 1.16-1.59), endocrine-metabolic (6.03, 4.13-8.82), circulatory (1.85, 1.56-2.20), respiratory (5.85, 3.89-8.80), digestive (5.64, 3.13-10.18), genitourinary (2.61, 1.20-5.69) and external causes (2.06, 1.55-2.72). Underweight was also associated with an increased risk of nonpremature death in four chapters and seven diseases. In contrast, obesity was only associated with increased risks of premature and nonpremature death in two and one chapters, respectively. Among Chinese female healthy never-smokers, underweight was an important risk factor for all-cause and multiple cause-specific mortality, especially the risk of premature death. While addressing the global obesity epidemic, the negative health consequences of low weight should not be ignored.
Immune checkpoint inhibitors (ICIs) have revolutionised cancer treatment. Previous studies suggested that early time-of-day administration is associated with better outcomes. We performed a retrospective study in patients treated at a large tertiary cancer centre. Patients receiving ICIs between January 2018 and December 2023 were grouped according to whether they had ≥50% ("late group") or <50% ("early group") of cycles after the median time of all treatments. The endpoint was overall survival (OS). Hazard ratios (HRs) were estimated using Cox models with and without time-dependent variables. 2631 patients with advanced/metastatic lung cancer (45%), melanoma (23%), renal carcinoma (18%), head and neck (9%), and urothelial cancer (5%) were included. Median age was 68.2 years and median infusion time was 12:49 h. At a median follow-up of 32 months, median OS was 13.1 (95% CI 11.8-14.4) vs 21.4 (19.8-24.5) months for late and early group. Late group was associated with shorter OS on both the standard analysis (HR 1.48, 1.33-1.63) and the time-dependent model (HR 1.30, 1.16-1.44). This study provides further evidence in favour of early ICIs administration with a large sample size and a time-dependent model, which reduces the risk of immortal time bias. Data from randomised trials are required to confirm these findings.
Advances in surgical techniques and neoadjuvant care for rectal cancer have increased sphincter preservation, allowing restoration of bowel continuity through low anterior resection (LAR). However, up to 75% of patients experience low anterior resection syndrome (LARS), which is bowel dysfunction characterised by faecal incontinence, frequency, urgency and clustering of bowel movements, significantly impairing quality of life (QoL). Current management is largely empirical, using lifestyle or pharmacological strategies with variable success. Transanal irrigation (TAI) is a non-surgical intervention that allows controlled colonic washouts, improving symptom control. Evidence supporting TAI for LARS is limited by small sample sizes and is primarily observational, highlighting the need for a rigorous randomised controlled trial (RCT). This study aims to compare TAI with conventional LARS care on QoL, bowel function, faecal incontinence and satisfaction in adults with LARS following LAR. This is a pragmatic, multicentre, crossover RCT conducted at eight academic hospitals across Quebec, Ontario and British Columbia, Canada. Eligible participants are adults (≥18 years) with an LARS score >20, at least 6 months post-LAR and without an ostomy or active colorectal complications. Participants will be randomised to receive either 3 months of daily TAI or conventional LARS care, followed by a 1 month washout and crossover to the alternate intervention. The TAI intervention includes an irrigation system, access to a web-based educational platform and virtual training with a research team member. Primary outcome is difference in global QoL between interventions, assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Secondary outcomes include bowel function (LARS score), faecal incontinence (Cleveland Clinic Faecal Incontinence Score) and satisfaction. Sample size (n=66, accounting for 10% attrition) was determined using Monte Carlo simulations to detect a 6-point difference in QoL with 85.8% power. Data will be analysed using linear mixed-effects models accounting for period, treatment and sequence effects. All study data will be collected via Research Electronic Data Capture and maintained in secure, password-protected systems; participant confidentiality will be ensured throughout. Safety monitoring will include training on proper TAI technique and reporting of adverse events. The study has received ethics approval from each participating site. The trial adheres to the Canadian Tri-Council Policy Statement on the use of human participants in research. Findings will be disseminated through peer-reviewed journals, conference presentations and scientific meetings, with authorship following the International Committee of Journal Editors guidelines. NCT05007015.
Limited knowledge exists on the association between hospital contacts before a childhood cancer diagnosis and the risk of early mortality. We conducted a register-based cohort study including 14,089 children with cancer diagnosed in 1989 - 2014 in Denmark and Sweden. Odds ratios (ORs) and 95% confidence intervals (CIs) of early mortality (deaths within 0-90 days) were estimated by nights in hospital up to two years prior cancer diagnosis and diagnoses within specific main diagnostic categories using logistic regression. Children hospitalized ≥14 nights within 2 years-14 days and 3 months-14 days before cancer diagnosis faced elevated ORs of early mortality (4.6, 95% CI 3.2-6.4; 4.4, 2.9-6.7). The association was not explained by maternal education. Early mortality was associated with diagnoses within several diagnostic categories prior to cancer diagnosis, including infectious (OR 1.5, 95% CI 1.1-2.0) and endocrine diseases (OR 1.6, 95% CI 1.02-2.5), blood (OR 3.3, 95% CI 2.1-5.1) and digestive disorders (OR 1.9, 95% CI 1.4-2.6), and symptoms with no specific diagnosis (OR 1.4, 95% CI 1.1-8). Children with increased time in hospital before cancer diagnosis had a higher risk for early mortality, which indicates underlying health vulnerabilities or pre-existing fragility in this population.
Older patients are routinely excluded from clinical research, limiting understanding of recurrence and mortality in colorectal cancer (CRC) patients over 75 who undergo curative major resection. Using linked data from national cancer, treatment and administrative datasets, we estimated recurrence, CRC-related and non-CRC mortality to 5 years after surgery for patients selected for curative resection in England between 2014 and 2020, who survived >9months. Recurrence was defined using diagnostic and treatment codes. 50,480 patients had curative resection, 15,496 (30.7%) aged >75. Recurrence-free survival at 5-years after resection was 66.2% (95%CI: 65.4%, 67.0%) for patients aged >75 and 77.4% (77.0%, 77.9%) for patients aged 18-75. By 5-years, 13.3% (12.7%, 13.9%) of the older group had died from CRC and 14.2% (13.6%, 14.8%) from non-CRC causes, compared with 7.7% (7.4%, 8.0%) and 3.6% (3.4%, 3.8%) respectively in the younger group. Recurrence-free survival was 22% lower for cancer stage 3 versus stage 1, and 12-13% lower for patients aged >75 versus ≤75. Cancer stage was the strongest predictor of recurrence and CRC-related death. In patients selected for surgery, those aged>75 had similar recurrence risk to younger patients, but higher risk of death following recurrence, and were as likely to die from other causes as from CRC.
The concurrent rise in metabolic syndrome (MetS) and the changing age profile of colorectal cancer (CRC) necessitates clarifying the heterogeneity in their association across demographic groups. This study aimed to define the precise age- and sex-specific associations between MetS and CRC risk, addressing a key gap to inform targeted prevention paradigms. In this cohort study, we analysed data from UK Biobank participants aged 40-69 years (recruited 2006-2010). Participants were stratified by age (<60 or ≥60 years) and sex into four groups. Multivariable Cox proportional hazards models were used to assess the associations of MetS, the number of metabolic abnormalities, and each component with CRC incidence. Among 379,173 participants, 4971 developed CRC during a median follow-up of 11.8 years. MetS was most strongly associated with CRC in younger males (hazard ratio [HR] 1.31, 95% CI 1.15-1.50), significantly in older adults of both males (HR 1.18, 95% CI 1.07-1.30) and females (HR 1.18, 95% CI 1.05-1.33), but not in younger females (HR 1.05, 95% CI 0.89-1.25). Older males but not females showed increasing risks when having 3, 4, and 5 abnormalities compared to none, respectively. Beyond younger females, elevated waist circumference was the sole component consistently linked to higher risk. The association between MetS and CRC is strongly dependent on age and sex in White populations, with the highest risk concentrated in young and middle-aged males. These findings directly support risk-stratified prevention and provide crucial clues for investigating the underlying sex- and age-specific biological mechanisms.
Obesity is a risk factor for pancreatic cancer, but mechanisms remain unclear. We investigated how anthropometric traits, individually and combined, relate to pancreatic cancer risk and whether associations are mediated by metabolic biomarkers. We analysed 462,300 adults (40-69 years) in the UK Biobank. Principal component analysis derived three body shape phenotypes combining body mass index (BMI), height, weight, waist and hip circumference, and waist-to-hip ratio (WHR). Mediation was assessed using four-way decomposition. Over a median follow-up of 10.9 years, 1115 pancreatic cancer cases occurred. Each one-standard-deviation (SD) increase in BMI or WHR was associated with a higher incidence of pancreatic cancer, with hazard ratios (HRs) of 1.20 (confidence interval, CI: 1.12-1.28) and 1.24 (CI: 1.14-1.36), respectively. Body shape characterizing overall obesity showed a similar association (HR = 1.20; CI: 1.12-1.28 per 1-SD), with glucose and HbA1c accounting for mediated proportions (mediated interaction + pure indirect effect) of 12.2% (CI: 3.4-21.0%) and 15.0% (CI: 5.7-24.2%), respectively. For BMI, glucose accounted for 15.9% (CI: 2.8-28.9%) and HbA1c for 20.0% (CI: 6.3-33.7%) of the association. Glucose and HbA1c mediate a large proportion of the obesity-pancreatic cancer association, highlighting the important role of glycemic control in obesity-related pancreatic carcinogenesis and targeted interventions in at-risk populations.
Aldo-keto reductase 1B10 (AKR1B10) is a novel serum marker for hepatocellular carcinoma (HCC). This study was aimed to evaluate its clinical value in the diagnosis and immediate postoperative monitoring for HCC. A total of 1197 subjects were recruited from two study centers, including 185 patients with HCC who underwent radical resection and followed up for 3 months. Serum samples were collected from all participants for AKR1B10 and alpha-fetoprotein (AFP) tests, and imaging and clinical data were collected. Serum AKR1B10 in HCC patients markedly increased to 1384.31 ± 107.91 pg/ml. Receiver operating characteristic (ROC) curve analysis showed an area under curve (AUC) of 0.877, sensitivity of 71.2%, and specificity of 97.2% for AKR1B10 in HCC compared to 0.792, 62.7%, and 88.7% for AFP. For early HCC, serum AKR1B10 had an AUC of 0.855, sensitivity of 70.6%, and specificity of 94.4% compared to 0.744, 56.7%, and 86.7% for AFP. After radical resection of HCC, serum AKR1B10 rapidly decreased to the normal range within 3-5 days whereas AFP remained high. At 1-3 months after surgery, serum AKR1B10 was consistent with imaging data in 89.11% of patients with HCC, whereas AFP had only 70.41%. AKR1B10 is an effective serum marker for diagnosis of HCC and postoperative monitoring of HCC, with better clinical performance than AFP.
Kaposi's sarcoma (KS) is the most common malignancy occurring in people living with HIV (PLWH). The clinical course of KS in PLWH established on combined anti-retroviral therapy (cART) resembles that of classic KS. To compare the clinical and biological characteristics of HIV-associated KS in patients with well-controlled viral infection (N = 21) and non-HIV-associated KS (N = 19). Clinical data were prospectively collected from patients treated at the National Centre for HIV malignancies at Chelsea & Westminster Hospital. Targeted transcriptomic analysis and multiplex immune-fluorescence were performed on archival tumour samples. Clinical outcomes were comparable between groups. The tumour microenvironment (TME) of non-HIV-associated KS was characterised by transcriptional upregulation of pathways associated with adaptive and innate immunity and angiogenesis. The TME of HIV-associated cases was associated with lower infiltration of activated CD4 cells. In both cohorts, we found the expression of HHV-8 genes to positively correlate with activated CD4, CD8, NK and immune checkpoint gene expression. The KS TME in the presence of well-controlled HIV infection is characterised by a lower degree of inflammation and more pronounced epithelial to mesenchymal transition. We also identified intra-tumoral HHV-8 gene expression as a driver of TME composition.
Lung cancer (LC) remains the deadliest cancer, often diagnosed at advanced stages. Screening reduces mortality in high-risk individuals. Eligibility criteria in European and US screening guidelines have recently expanded. Therefore, we conducted an updated systematic review of risk-based models for identifying candidates for low-dose computed tomography screening and post-screening nodule classification. We systematically searched Embase and Medline (January 2020-January 2026), identifying studies proposing new risk models in the context of LC screening. We separated models by pre- and post-screening risk stratification. Data extraction included study design, population, model type, risk horizon and model performance metrics. We performed an exploratory meta-regression of areas under the curve (AUCs) to assess whether sample size, model type, validation type and inclusion of biomarkers were associated with performance. Of 2462 records, 91 were included. 56 models were for screening selection (30 included biomarkers) and 35 for post-screening nodule classification. Regression-based models predominated, though machine-learning approaches were increasingly common. Discrimination ranged from moderate (AUC∼0.70) to excellent (>0.90), with biomarker and imaging-enhanced models often outperforming models without. Calibration was inconsistently reported and fewer than half underwent external validation. We identified 91 risk prediction models for LC, developed after 2020. Although many demonstrated promising discrimination across both screening selection and post-screening management, most remain insufficiently mature for clinical adoption, as their performance and practical value outside the original study setting are uncertain. Future work should prioritise external validation, updating and comparative evaluation of existing models, and prospective implementation studies rather than continued development of additional models.