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Chemotherapy-induced neutropenia and febrile neutropenia (FN) remain consequential toxicities in breast cancer treatment, driving infections, unplanned care, and compromises in planned dose intensity. Long-acting granulocyte colony-stimulating factor (G-CSF) enables once-per-cycle prophylaxis and has become central to FN prevention strategies, particularly in dose-dense and high-risk regimens. Beyond efficacy, the supportive care evidence base has rapidly expanded to implementation in routine practice, delivery devices, biosimilars, safety surveillance, and value-based decision-making. However, this heterogeneous and fast-growing literature has not been systematically mapped to support evidence navigation and identify actionable research priorities. We therefore conducted a bibliometric analysis to characterize the knowledge structure, influential contributors, and emerging hotspots of long-acting G-CSF prophylaxis research in breast cancer chemotherapy. Publications were retrieved from the Science Citation Index Expanded of the Web of Science Core Collection using a topic strategy combining breast cancer, chemotherapy-induced context, long-acting G-CSF agents, and neutropenia/FN prophylaxis concepts. The search was performed on 24 February 2026 and covered 2002-2025. English-language records were included; document types were limited to articles and reviews, with meeting abstracts, editorial materials, and letters excluded during screening. Bibliometrix, VOSviewer, and CiteSpace were applied to evaluate annual production, collaboration networks, keyword co-occurrence, co-citation structure and evolution, burst detection, and thematic mapping. The WoSCC retrieval returned 555 records; after restricting to English (547) and excluding meeting abstracts (n = 39), editorial materials (n = 5), and letters (n = 7), 496 publications were included (412 articles; 84 reviews). Annual production increased and entered a sustained high-output phase in the late 2010s and early 2020s. The USA was the most productive country (218 documents; 10,188 citations), followed by Germany (69) and England (51). Supportive Care in Cancer contributed the most publications (62), while Annals of Oncology had the highest citations among the top journals (1489). Co-citation and keyword analyses indicated an evolution from early trial- and guideline-driven supportive care toward optimization in routine practice, real-world prophylaxis evaluation, biosimilars, safety, and cost-effectiveness. The evidence landscape of long-acting G-CSF prophylaxis in breast cancer chemotherapy has evolved from efficacy confirmation toward implementation-oriented supportive care. Current research increasingly emphasizes real-world effectiveness, safety monitoring, biosimilar integration, delivery models, and value-based considerations. By mapping knowledge structures and emerging priorities, this study may provide a structured overview for evidence navigation and may help identify future research priorities, particularly in relation to real-world utilization, affordability, guideline-concordant use, and resource-sensitive febrile neutropenia prevention.
Liquid biopsy has become an increasingly important tool in clinical oncology due to the utility of circulating tumor DNA (ct-DNA). Plasma ct-DNA levels reflect the tumor burden of patients and provide valuable information for personalized treatment strategies. Colorectal cancer (CRC) is among the most frequently diagnosed malignancies worldwide and remains a leading cause of cancer-related mortality. The implementation of personalized therapy can notably improve clinical outcomes in these patients. The present study aimed to evaluate ct-DNA in patients with metastatic CRC undergoing therapy at the Department of Medical Oncology, University Hospital of Ioannina (Ioannina, Greece), using next-generation sequencing (NGS) to identify tumor mutations in both tissue and cell-free plasma DNA. A total of 45 patients newly diagnosed with metastatic CRC were enrolled in the current study. ct-DNA evaluation was performed at diagnosis, and both tissue and plasma samples were analyzed using NGS to assess the mutational profile. The most frequent mutation identified was in KRAS. A high level of concordance was observed between tissue and plasma samples regarding ct-DNA detection and mutational status. Sequential ct-DNA analysis during therapy revealed dynamic changes in mutation profiles over the course of treatment. In conclusion, liquid biopsy offers marked clinical value as a minimally invasive tool for personalized therapy in metastatic CRC. NGS-based liquid biopsy enables real-time evaluation of ct-DNA and mutation status during treatment, supporting therapeutic decision-making and disease monitoring.
Thousands of scholars across Europe faced discrimination for their heritage, especially Jewish heritage, throughout the 1930s. Hundreds of these persecuted academics worked in science and healthcare, often as primary researchers within a medical sub-specialty. In response, in 1933 British professors founded the Society for the Protection of Science and Learning (SPSL) with two objectives: raising funds to provide maintenance grants for displaced scholars and connecting scholars to academic placements worldwide. In this article, I analyze the stories of nineteen physicians fleeing fascist persecution in Europe through their 712 leaves of correspondence within the archive of the SPSL. I selected two medical subspecialties, to compare whether the well-funded field of oncology would have greater success placing refugees compared to the less academically-elevated field of orthopedic surgery. Through the first analysis of two complete medical subspecialty records from the SPSL archives, I examine how the SPSL faced difficulties deciding which colleagues to help financially and triaged levels of support. I also situate the experiences of the analyzed applicants within the context of British interwar medicine and academia, including British skepticism of foreign research and overlaps between SPSL leadership and the British eugenics movement. When funding ran low, the SPSL still assisted scholars through different channels, whether referring to other aid organizations, sending support letters to potential employers, or simply staying in contact. The surge in applications in 1938, five years after the organization's foundation, hindered scholars' chances as persecution increased and funding tapered. Importantly, the British medical establishment distrusted the overall research quality of many fleeing scholars and felt even less confident admitting medical practitioners who were not also researchers. Ultimately, medical scholars from fascist Germany and Austria who applied to the SPSL had a similar experience to other aspiring refugees seeking British assistance before 1939: they could not rely on Britain to support their immigration and predominantly settled elsewhere.
Ubiquitination and N6-methyladenosine (m6A) RNA methylation constitute two fundamental layers of post-translational and post-transcriptional regulation that coordinately govern gene expression in cancer. These regulatory systems exhibit intricate crosstalk, revealing that they frequently converge on shared oncogenic signaling pathways to fine-tune malignant cell behaviors. Cooperative regulation by ubiquitination and m6A is involved in modulating core cancer-driving circuits, including the PI3K-AKT and NF-κB pathways, thereby taking part in tumor cell proliferation, metastatic dissemination, immune evasion, metabolic adaptation and resistance to targeted therapies and chemotherapy. The interaction between them forms intricate feedback loops and exhibits context specificity, with the same regulatory axis capable of promoting or restraining tumorigenesis depending on cell types, mutation background and microenvironmental cues. Elucidating the molecular mechanisms underlying ubiquitin-m6A crosstalk is thus key for developing next-generation precision oncology strategies. Notably, components of these pathways such as ubiquitin ligases, deubiquitinases and m6A writers, erasers and readers, have been regarded as potential diagnostic biomarkers and therapeutic targets. Future advances relying on integrative multi-omics profiling, sophisticated functional models and rigorous in vivo validation are essential to unravel the complexity of these multi-layered regulatory networks. Such insights may ultimately enable the rational design of therapies that exploit ubiquitin-m6A crosstalk to more effectively suppress cancer progression.
Chromatin organization plays a fundamental role in the regulation and preservation of the eukaryotic genome. Histone variants contribute to chromatin dynamics by replacing canonical histones within nucleosomes and conferring specialized structural and regulatory properties. Among these variants, the centromere-specific histone H3 variant CENP-A is essential for establishing and maintaining centromere identity and ensuring accurate chromosome segregation during mitosis. Proper expression, deposition, and maintenance of CENP-A are tightly regulated through dedicated chaperones and mechanisms. Disruption of these regulatory processes can lead to aberrant CENP-A expression or mislocalization, resulting in defective centromere function and chromosome segregation. CENP-A is frequently overexpressed in several human cancers and CENP-A overexpression often correlates with tumor progression, chromosomal instability, and poor prognosis. Ectopic incorporation of CENP-A into non-centromeric chromatin can promote aberrant chromatin states and partial recruitment of kinetochore components. These alterations can disrupt normal kinetochore function and contribute to chromosome missegregation, thereby promoting chromosomal instability (CIN) and tumor evolution. In addition to its role in mitotic fidelity, emerging studies suggest that ectopic CENP-A can interfere with chromatin factors and influence transcriptional regulation. Hence, CENP-A emerges as a potential biomarker for cancer prognosis and therapeutic response. In this review, we summarize current knowledge on the regulation of CENP-A expression and deposition, discuss the functional consequences of its dysregulation in cancer, and highlight emerging clinical and translational implications of targeting centromere chromatin pathways in oncology.
Hereditary transthyretin amyloidosis (hATTR) is a progressive, multisystemic, and life-threatening disease that disproportionately affects individuals of African descent, with an estimated prevalence of 3.4% of Black Americans. hATTR is often mis- or underdiagnosed, partially because many of its symptoms overlap with other cardiac conditions. This study highlights additional factors that may be contributing to the underdiagnosis of hATTR in Black patients. Participants were ascertained from the Emory University Amyloidosis Clinic with purposive sampling. A total of 11 interviews were conducted via telephone, transcribed, and coded by two coders for thematic analysis. A Cohen's kappa of 0.74 was reached. The overwhelming majority of participants cited misdiagnosis, mistrust of healthcare providers, denial or misunderstanding of one's own health risks, and poor family communication as prevalent contributing factors to the underdiagnosis of hATTR. Participants cited appropriate referrals to heart failure providers and family letters as contributing factors to proper diagnosis of hATTR. Importantly, participants emphasized the need for more personal and intimate relationships with providers in order to improve uptake of genetic testing in this population. Participants suggested engaging directly with the Black community to improve trust. This study highlights the need for improvements to be made regarding the diagnosis of hATTR in the Black population. Participants suspected of having hATTR should be referred to a heart failure cardiologist for appropriate diagnosis. Genetic testing and follow-up genetic counseling is recommended to appropriately inform the patient of health risks for themselves and their family members.
Gestational trophoblastic disease (GTD) includes premalignant and malignant entities such as choriocarcinoma and invasive mole, collectively termed gestational trophoblastic neoplasia (GTN). While chemotherapy remains the standard treatment, hysterectomy is indicated in cases of chemoresistance, significant hemorrhage, or in patients with nonmetastatic GTN who do not desire fertility preservation. This review aims to assess the effectiveness of hysterectomy in treating GTN. A systematic literature search was conducted using PubMed, EBSCOHost, ProQuest, and Google Scholar for studies published from 27 February 2000 to 27 February 2024. Exclusion criteria included single case reports, editorials, commentaries, letters, non-peer-reviewed studies, non-full-text articles, and studies without hysterectomy or relevant outcome data. Eligible studies focused on GTN and reported on remission outcomes post-hysterectomy. Three reviewers independently extracted data and analyzed it using MedCalc v19.5.1. This review is registered with PROSPERO (CRD42024556274). Seven retrospective cohort studies involving 407 patients were analyzed. The overall complete remission rate following hysterectomy was 86.6%, with higher rates in nonmetastatic cases (99.5%) and lower in metastatic cases (46.3%). Complication and mortality rates were low, with deaths occurring primarily in metastatic or high-risk patients. Hysterectomy plays a significant role in managing select GTN cases, particularly nonmetastatic or chemotherapy-resistant disease, and when fertility preservation is not desired. However, its effectiveness is limited in metastatic GTN. Postoperative monitoring of serum hCG remains crucial due to the risk of residual or metastatic disease.
Lactylation, a novel post-translational modification, has emerged as a critical mechanistic link between metabolic reprogramming and epigenetic regulation in cancer. The present review aimed to synthesize emerging evidence on the role of lysine lactylation in the pathogenesis and progression of major digestive system malignancies, including esophageal, gastric, colorectal, hepatocellular and pancreatic cancer. The molecular mechanisms through which lactate-derived lactylation modifies histone and non-histone proteins are described, which thereby regulate key oncogenic processes such as metabolic adaptation, cancer stemness maintenance, epithelial-mesenchymal transition, immunosuppressive tumor microenvironment remodeling, angiogenesis, perineural invasion and therapeutic resistance. The translational potential of targeting the lactylation axis by inhibiting lactate production, blocking lactate transport or directly modulating lactylation-related enzymes are explored, and the development of lactylation-based prognostic models and their implications for innovative combination strategies to overcome treatment resistance are also highlighted. The present review highlights lactylation as a pivotal regulator in digestive oncology and a promising target for novel diagnostic and therapeutic strategies.
To better define the frequency and types of retinal pigment epithelial (RPE) tumors. Retrospective review of all computer-coded RPE tumors over a five-decade period. Of 926 consecutive patients with RPE tumors, the specific diagnosis included solitary congenital hypertrophy of the retinal pigment epithelium (n = 727, 79%), multifocal congenital hypertrophy of the RPE (n = 42, 4%), torpedo maculopathy (n = 7, 1%), RPE hamartomas associated with familial adenomatous polyposis (n = 10, 1%), congenital simple hamartoma of the RPE (n = 5, 1%), combined hamartoma of the retina and RPE (n = 99, 11%), benign RPE adenoma (n = 34, 3%), and malignant RPE adenocarcinoma (n = 2, <1%). There were differences in RPE tumors regarding patient age (P < 0.01), race (P < 0.01), sex (P < 0.01), presenting visual acuity (P < 0.01), number of tumors (P < 0.01), tumor basal diameter (P < 0.01), tumor thickness (P < 0.01), and distance to the optic disc (P < 0.01) and foveola (P < 0.01). There were differences in RPE tumors regarding imaging with ultrasonography (P < 0.01), optical coherence tomography (P < 0.01), and prevalence of macular epiretinal membrane, cystoid macular, edema, and subretinal fluid on optical coherence tomography (P < 0.01). By autofluorescence and fluorescein angiography, nearly all lesions that were imaged were hypoautofluorescent/hypofluorescent except for combined hamartoma of the retina and RPE (P < 0.01). Outcomes revealed visual acuity loss ≥3 lines (≥15 letters) at 10 years more often in combined hamartoma of the retina and RPE (20%), adenoma (21%), and adenocarcinoma (100%) (P < 0.01) and 10-year nodular growth in congenital hypertrophy of the RPE (1%), adenoma (9%), and adenocarcinoma (100%) (P < 0.01). Retinal pigment epithelial tumors comprise a spectrum in demographics, clinical features, and outcomes. Most remain stable over time with little impact on visual acuity except for combined hamartoma of the retina and RPE, adenoma, and adenocarcinoma.
[This corrects the article DOI: 10.3892/ol.2020.12321.].
The progression of lung adenocarcinoma (LUAD) is influenced by polyamine metabolism, which modulates antitumor immunity, although the underlying mechanisms remain unclear. The present study investigates the role of polyamine metabolism-related genes (PMRGs) in LUAD using transcriptomic data, single-cell RNA sequencing (scRNA-seq) and Mendelian randomization. Differentially expressed PMRGs were identified through differential expression analysis and weighted gene co-expression network analysis. Prognostic genes were selected via Cox regression and least absolute shrinkage and selection operator regression to construct a risk model. Immune infiltration, machine learning and scRNA-seq were employed to explore molecular mechanisms whilst reverse transcription-quantitative PCR (RT-qPCR) validated gene expression in LUAD tissues. A nomogram incorporating risk scores assisted in predicting LUAD prognosis (area under the curve >0.6). Distinct immune cell profiles, particularly involving B cells and CD4+ T cells, were observed between high- and low-risk groups. Drug sensitivity analysis identified 15 drugs with differential responses. Epithelial cells emerged as a key cluster, with dynamic changes in calcium voltage-gated channel auxiliary subunit α2δ2 (CACNA2D2) expression during pseudotime. RT-qPCR confirmed the downregulation of prognostic genes in LUAD. A polyamine metabolism-related prognostic signature (CACNA2D2, adenoreceptor β-1, immunoglobulin superfamily member 10 and carbonic anhydrase 4) associated with the tumor microenvironment was established, offering potential for enhanced prognosis prediction in LUAD.
Lung squamous cell carcinoma (LUSC) is a prevalent subtype of lung cancer, which is primarily characterized by poor prognosis due to the lack of targeted therapies, while a large proportion of patients show limited response to chemotherapy. The present study aimed to identify predictive chemotherapy biomarkers based on genomic alterations in LUSC. Non-negative matrix factorization clustering was applied to classify patients with LUSC into distinct subgroups based on genomic alterations. Subsequently, chemotherapy efficacy was predicted via exploring gene signatures, and the results were validated using The Cancer Genome Atlas database (TCGA). A total of four distinct clusters were classified. Cluster 1 and TP53 loss-of-function (TP53 LOF) variations were each independently associated with poor prognosis, irrespective of clinical stage. Based on the molecular characteristics of the initial clusters, the classification was further refined by further incorporating TP53 LOF and gene amplification (amp). Patients without TP53 LOF, who harbored amplification of at least one of nine specified genes [PIK3 catalytic subunit, cyclin D1, fibroblast growth factor (FGF) 19, FGF3, FGF4, FGF receptor 1, kinase insert domain receptor, KIT proto-oncogene and platelet derived growth factor receptor α] displayed the longest progression-free survival (PFS). By contrast, patients with TP53 LOF but lacking amplification of at least one of nine genes [Amp(9G)] exhibited the worst overall survival compared with the other subgroups. Validation in the TCGA database confirmed the prognostic significance of this classification, with Amp(9G) without TP53 LOF predicting the most favorable PFS, and TP53 LOF without Amp(9G) indicating the least favorable PFS. Therefore, a composite biomarker integrating Amp(9G) and TP53 LOF was identified as a prognostic indicator for patients with LUSC treated with first-line chemotherapy. Overall, the results of the present study suggest that the absence of TP53 LOF combined with the presence of Amp(9G) could be associated with improved response to first-line chemotherapy in LUSC.
Recent neoadjuvant trials in lung cancer have demonstrated meaningful survival advantages, highlighting the need for standardized assessment of pathologic response in resected specimens. Only two systems are currently recommended for evaluating post-treatment response, namely the International Association for the Study of Lung Cancer (IASLC) tumor regression grading system and the immune-related pathologic response criteria (irPRC). The present study aimed to review and apply histopathologic parameters for assessing tumor regression in non-small cell lung carcinoma (NSCLC) specimens resected after neoadjuvant therapy. A total of 30 NSCLC resections obtained after neoadjuvant therapy between 2022 and 2025 were analyzed. Gross and microscopic evaluations were performed according to IASLC recommendations. Residual viable tumor, fibrosis, inflammation and necrosis were semi-quantitatively assessed according to IASLC and irPRC principles. Major pathologic response (mPR) was defined as ≤10% viable tumor and pathologic complete response (pCR) as 0% viable tumor. Associations with demographic features, treatment modalities and survival outcomes were analyzed. Compared with chemotherapy (CT) alone, chemo-immunotherapy (CIT) exhibited a trend toward a deeper pattern of tumor regression, reflected by lower median viable tumor percentages (7.5 vs. 55.0%) and higher mPR rates (62.5 vs. 22.7%), although these differences did not reach statistical significance. pCR occurred in 37.5% of patients treated with CIT and in 13.6% of patients treated with CT. CIT specimens demonstrated more prominent immune-mediated stromal changes, including greater intratumoral inflammation (32.5 vs. 10.0%) and more frequent lymphocytic patterns. Fibrosis strongly correlated with response (P<0.001), whereas necrosis did not. Spread through air spaces positivity was found to be significantly reduced in cases of mPR (P<0.001). Therefore, neoadjuvant CIT may be associated with deeper pathologic regression compared with CT, characterized by increased fibrosis and immune activation. Major pathologic response remains a potential prognostic indicator and integration of IASLC and irPRC criteria, together with tumor microenvironment assessment, may improve the evaluation of treatment response in resectable NSCLC.
Tongue squamous cell carcinoma (TSCC) remains a significant clinical challenge, owing to its high prevalence and poor prognosis. Cancer stem cells (CSCs) serve a critical role in driving the initiation and progression of TSCC. The present review examined the unique characteristics and functional dynamics of CSCs in TSCC, with particular emphasis on the molecular signaling pathways that regulate their behavior. Key pathways, including Wnt/β-catenin, Notch and Hedgehog signaling pathways, are explored to provide a comprehensive understanding of the mechanisms underlying TSCC. The present study was reported in accordance with the Preferred Reported Items for Systematic Reviews. Articles were sourced from PubMed (pubmed.ncbi.nlm.nih.gov/) using the search terms 'tongue squamous cell carcinoma', 'cancer stem cells', 'molecular signaling', 'Wnt/β-catenin', 'Notch', 'Hotch' and 'Hedgehog', covering the period from January 2001 to October 2025. The review was limited to papers published in English. A total of 437 studies was retrieved. Excluding those studies are not closely related to the topic, 138 were reviewed in detail for their originality and relevance to the broader scope of the present review. By mapping these key signaling networks, the present review aimed to provide a strong foundation for the development of precision therapeutic strategies targeting TSCC.
Background: Workplace victimization is a form of repeated and systematic psychological violence that can severely affect both mental and physical health. From a psychological perspective, it impacts mood states, defense mechanisms, and personality functioning. Methods: This cross-sectional study investigated the psychological and behavioural correlates of workplace victimization in a sample of 33 workers from various professional sectors, using a multidimensional assessment including standardized measures of personality traits, mood states, and defense mechanisms. Results: The MMPI-2 profile revealed elevated scores in Hypochondriasis (Hs: 72.00), Depression (D: 70.21), Hysteria (Hy: 67.61), and Paranoia (Pa: 68.76), indicating somatic symptoms, depressive features, and suspiciousness. The POMS showed increased Tension-Anxiety (T: 65.06), Depression-Dejection (D: 68.21), Anger-Hostility (A: 68.15), and Fatigue-Inertia (F: 65.24), alongside reduced Vigor-Activity (V: 43.18). The DMI analysis highlighted a high Reversal score (REV: 65.91), suggesting a predominant use of defense mechanisms such as altruism and idealization to cope with distress. Conclusions: In this selected sample of adults referred for psychological evaluation for suspected or documented workplace victimization, participants showed a clinically relevant psychological burden, including depressive symptoms, somatic concerns, Anger-Hostility, fatigue, reduced vigor, and specific defensive patterns. Given the cross-sectional design, small sample size, and absence of a control group, these findings should be interpreted as preliminary and cannot establish causality or the specificity of this profile to workplace victimization.
Chromosomal alterations are key in the study of acute lymphoblastic leukemia (ALL) as they facilitate the establishment of risks, prognosis and treatment. The intrachromosomal amplification of chromosome 21 (iAMP21) can generate a structurally heterogeneous derivative chromosome 21 that can typically replace a normal chromosome 21 and defines a subtype of high-risk childhood ALL (iAMP21-ALL). A region commonly involved in this amplification has been delineated and includes genes such as chromatin assembly factor 1 subunit B, dual-specificity tyrosine-(Y)-phosphorylation regulated kinase 1A, erythroblast transformation-specific-related gene, high mobility group nucleosome binding domain 1 and Runt-related transcription factor 1, but its role in the development of leukemia has not yet been fully elucidated. The Down syndrome critical region on chromosome 21 (ripply transcriptional repressor 3) overlaps with a common amplification region in iAMP21. Therefore, it has been hypothesized that iAMP21-related genes may be associated with Down syndrome susceptibility to ALL. The present review described the biological role of iAMP21-related genes and their relationship with ALL development.
[This corrects the article DOI: 10.3892/ol.2021.12593.].
Diffuse large B-cell lymphoma (DLBCL) is clinically heterogeneous and existing prognostic indices incompletely capture its biological diversity. The present study aimed to investigate how transcriptome-inferred LymphoMAP archetypes (lymph node-like, fibroblast-macrophage-rich and T cell-exhausted) relate to genetic subtypes and immune evasion-associated programs, and whether integrating these dimensions improves risk stratification beyond the International Prognostic Index (IPI). Using the DLBCL-2018 cohort (n=562), LymphoMAP archetypes were inferred and immune programs were quantified by single-sample gene set enrichment analysis, summarizing them into an immune evasion-associated index. In the immunochemotherapy-treated subset (n=234), overall survival was assessed and an elastic-net Cox model was developed to derive a transcriptomic risk score (RScore-Expr). The score was externally evaluated in four independent Gene Expression Omnibus cohorts (n=1,173) with a random-effects meta-analysis performed across studies. LymphoMAP archetypes were non-randomly associated with genetic subtypes (χ2=20.85, P=0.0076) and exhibited distinct immune-program patterns. While archetypes alone were not prognostic in the treated subset (log-rank P=0.67), an integrated model identified high-risk patients (log-rank P=0.0026) with modest discrimination (C-index: 0.624; time-dependent area under the curve values: 0.662/0.628/0.642 at 12/36/60 months). When added to the IPI, the score improved corrected discrimination (0.639 to 0.687), improved model fit (likelihood-ratio χ2=12.32, P=4.48×10-4), and yielded higher net benefit on decision-curve analysis at 24 and 60 months. In external cohorts, RScore-Expr showed a consistent association with survival (pooled hazard ratio per 1 standard deviation, 1.13; 95% confidence interval 1.01-1.26; P=0.033). These results support a cross-platform framework linking microenvironment archetypes, immune evasion-associated programs and tumor genetics. The novelty of the current study lies in integrating these features into an externally evaluated transcriptomic risk score and formally demonstrating added value beyond the IPI in DLBCL.
PIK3CA serves a well-established role in carcinogenesis; however, although its prognostic importance in cervical squamous cell carcinoma (SCC) has been extensively studied, the results remain controversial. In the present single-institution study, the clinicopathological features of 207 cases of cervical SCC were characterized based on their PIK3CA hotspot mutational status. The prevalence of PIK3CA hotspot mutations in this cohort was 13% (27/207), with 96.3% (26/27) of mutations clustered in the helical domain (exon 9). Patients harboring PIK3CA mutations tended to be older, and the mutation rate was significantly higher among those aged ≥50 years compared with those aged <50 years (18.4% vs. 8.3%, P=0.031). When stratified by stage, a trend toward a higher frequency of PIK3CA mutations was observed in patients with advanced-stage disease (P=0.0575), although this difference did not reach statistical significance. The mutation rate was 6.8% (5/74) among patients with stage I carcinoma and increased to 18.1% (19/105) among those with stage II or higher disease (P=0.0284). Nearly all patients with PIK3CA-mutant tumors (96%, 23/24) underwent chemotherapy and/or radiation therapy (P=0.0089). No statistically significant difference was observed between patients with PIK3CA-wildtype and PIK3CA-mutant tumors with respect to ethnicity, procedures performed at initial diagnosis or human papillomavirus status. Programmed death-ligand 1 (PD-L1) expression (combined positive score ≥1) was observed in 76.3% of cervical SCC cases. However, immunohistochemical analysis did not reveal a statistically significant association between PD-L1 expression and PIK3CA mutation status. Furthermore, the results showed that PIK3CA mutations were not associated with the prognosis of patients with cervical SCC. The only factor significantly associated with the cause-specific survival and overall survival in this cohort was clinical stage. The present study highlights and expands upon the clinicopathological characteristics of cervical SCC with PIK3CA hotspot mutations in a single-institution cohort. Future studies should focus on evaluating the efficacy of PI3K inhibitors, alone or in combination with immunotherapy and other targeted treatments, in selected patients. This evaluation should be based on molecular alterations that may predict therapeutic benefit.