Aug 2026· Oncology Research· Vol 34, pp. 1-10· 0 citations· 33 references
Medicine
TL;DR
IL31RA polymorphisms may be associated with an increased propensity for lymph node involvement, particularly in gingival cancer, suggesting that IL31RA may have potential clinical relevance in OCSCC progression.
Abstract
Background: Interleukin-31 receptor alpha (IL31RA) has been implicated in cancer progression and tumor cell migration, but its genetic associations across cancers remain unclear. This study aimed to examine IL31RA polymorphisms in relation to lymph node involvement in oral cavity squamous cell carcinoma (OCSCC). Methods: In this case-control study, 2845 participants were enrolled, including 1352 patients with OCSCC and 1493 cancer-free controls. Associations between IL31RA SNPs and OCSCC susceptibility and clinicopathological characteristics were evaluated. Functional analyses, including cell migration assays, together with bioinformatic database analyses, were performed to investigate the biological significance of IL31RA and genotype–expression correlations. Logistic regression and other appropriate statistical methods were used to assess these associations. Results: IL31RA polymorphisms did not significantly influence OCSCC development. However, subsite-specific analysis revealed that gingival cancer patients with minor alleles at rs6876491 and rs10055201 had significantly higher lymph node involvement rates than wild-type carriers. IL31RA rs6876491 was also an independent predictor of lymph node involvement in gingival cancer after adjusting for clinical characteristics, with adjusted odds ratios of 2.172 (95% Confidence Interval: 1.095–4.310). Bioinformatic databases also showed that minor genotypes correlated with increased IL31RA expression. Patients with higher IL31RA expression tended to have poorer survival in head and neck squamous cell carcinoma (HNSCC) based on TCGA public database analyses (p = 0.053). Moreover, functional studies confirmed that IL31RA overexpression enhanced cellular migration (p < 0.05), while knockdown suppressed migratory capacity (p < 0.05). Conclusions: IL31RA polymorphisms may be associated with an increased propensity for lymph node involvement, particularly in gingival cancer, suggesting that IL31RA may have potential clinical relevance in OCSCC progression.
Background: Death-associated protein kinase 1 (DAPK1) is a key regulator of apoptosis and immune responses; however, its prognostic significance in oral cancer remains insufficiently characterized. This study investigated the prognostic relevance of DAPK1 in oral squamous cell carcinoma (OSCC) and examined its associations with immune infiltration and apoptosis-related signaling pathways. Methods: A retrospective translational study design was employed, integrating TCGA-based expression and methylation analyses of 528 head and neck squamous cell carcinoma (HNSCC) tumors, UALCAN epigenetic profiling, GeneMANIA protein–protein interaction mapping, TIMER 2.0 immune correlation analyses in 422 HPV-negative HNSCC patients, and multiplex immunofluorescence validation using a tissue microarray cohort of 82 patients with histologically confirmed OSCC, of whom 75 were eligible for the final analysis at Kaohsiung Veterans General Hospital, Taiwan. Results: In vitro validation using Western blot analysis in FaDu cells showed that epidermal growth factor receptor (EGFR) inhibition with gefitinib induced upregulation of DAPK1 protein expression at 10 μM and increased total caspase-3 expression. Higher DAPK1 signal in whole-field quantification was associated with increased CD4+ and CD8+ T-cell infiltration and enrichment of apoptosis-related pathways. Patients with high DAPK1 expression demonstrated a consistent protective trend for overall survival in a pre-specified fully adjusted primary model (adjusted HR = 0.51, 95% CI: 0.21–1.21, p = 0.126), and exhibited significantly improved survival in a secondary parsimonious model (adjusted HR = 0.41, 95% CI: 0.18–0.91, p = 0.029). Multiplex immunofluorescence further confirmed stronger DAPK1 and caspase-3 staining, along with denser lymphocytic infiltration within the tumor microenvironment. Conclusions: Collectively, these findings suggest that DAPK1 is associated with apoptosis-related signaling, increased immune-cell infiltration, and favorable clinical outcomes in OSCC, although its independent prognostic value requires validation in larger cohorts.
Objective: Laryngeal cancer is an aggressive malignancy in which immune regulatory mechanisms play a critical role in tumor progression and recurrence. The OX40/OX40L axis, a member of the tumor necrosis factor superfamily, has been implicated in immune modulation however, its genetic and soluble profiles in laryngeal cancer remain insufficiently characterized. Beyond cancer susceptibility, the clinical relevance of OX40/OX40L alterations in recurrence biology remains poorly understood.\Materials and Methods: In this study, we investigated the distribution of OX40 rs17568 and OX40L rs1234313 polymorphisms and evaluated their association with serum soluble OX40 (sOX40) and OX40L (sOX40L) levels in 80 patients with laryngeal cancer and 111 healthy controls. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR--RFLP), and soluble protein levels were quantified by enzyme-linked immunosorbent assay (ELISA).\Results: No significant differences in serum sOX40 or sOX40L levels were observed between patients and controls. While OX40 rs17568 genotype distributions were comparable between groups, a significant difference was detected for OX40L rs1234313, with homozygous genotypes (AA and GG) being more frequent in laryngeal cancer patients (p=0.007). Although genotype distributions were not associated with clinicopathological parameters, circulating sOX40 levels were significantly higher in patients with disease recurrence than in those without recurrence (p=0.008).\Conclusion: The findings suggest that alterations in the OX40/OX40L axis may be associated with immune dysregulation during disease progression rather than cancer initiation in laryngeal cancer. Particularly, elevated circulating sOX40 levels were associated with disease recurrence. Given the cross-sectional and exploratory nature of the study, these findings should be interpreted with caution and require validation in larger prospective cohorts.
I. Yaylim, Maral Farzam, Dilara Sönmez Zor et al.· Experimed· 0 citations
BACKGROUND
The specific effect of the LINC00673 rs9914618 single nucleotide polymorphism (SNP) on lung squamous cell carcinoma (LUSC) remains unclear. This study aims to evaluate its association with LUSC susceptibility and prognosis.
MATERIALS AND METHODS
We recruited 305 LUSC patients and 336 healthy controls. LINC00673 expression was measured by qRT-PCR. The rs9914618 genotype was determined using TaqMan assays. Disease-free survival was estimated by Kaplan-Meier analysis. Multivariate Cox regression yielded hazard ratios with 95% confidence intervals.
RESULTS
LINC00673 expression was significantly upregulated in LUSC tissues and serum relative to the control group. The A allele at rs9914618 was positively associated with increased LINC00673 transcription. Carriers of the A allele or AA genotype had a higher risk of LUSC. Patients with GA or AA genotypes showed more severe clinicopathological features and lower five‑year survival rates. The rs9914618 polymorphism was validated as an independent prognostic factor.
CONCLUSION
The LINC00673 rs9914618 polymorphism may serve as a potential prognostic factor for LUSC, showing significant associations with patient outcomes and risk stratification.
Xing-Shu Zhang, Fen Wang, Licai Zhang et al.· Expert Review of Molecular D...· 0 citations
Urothelial bladder carcinoma (UBC) is the ninth most common malignancy worldwide and ranks thirteenth in cancer-related mortality. A significant challenge in managing non-muscle-invasive UBC (NMIBC) is the high recurrence rate, compounded by a paucity of robust prognostic biomarkers. Given that evasion of apoptosis is a hallmark of carcinogenesis, the apoptosis regulator BCL-2 oncogene plays a critical role by negatively regulating the intrinsic apoptotic pathway, often leading to protein overexpression and malignant cell immortalization. Methods and Results: This study evaluated the BCL-2 allelic variants rs2279115 (G > T) and rs3943258 (T > C), including their haplotype structures, in association with BCL-2 immunohistochemical expression in UBC patients. Genetic and immunostaining data were analyzed alongside prognostic factors, environmental exposure, and clinical history. Furthermore, we sought to exhibit BCL-2 immunohistochemical staining patterns via immunofluorescence in selected samples. Our findings revealed that the rs2279115 variant is significantly associated with BCL-2 positive expression. Specifically, the TT genotype in the genotypic model (p = 0.035) and the GT genotype in the overdominant model (p = 0.045) were linked to protein status. Additionally, the CT haplotype was independently associated with high-grade tumors. Conclusions: The presence of the CT haplotype — in either homozygosity or heterozygosity — exerted a risk effect of high-grade (p = 0.020). In conclusion, these findings suggest that BCL-2 variants, haplotype structures, and immunohistochemical expression may offer relevant insights into the molecular characteristics of urothelial bladder cancer. Further prospective validation is needed to determine whether BCL-2 profiling can serve as a useful complementary tool for risk assessment in clinical practice.
Julia Ayumi Ikeda Kawasaki, Ariane Pereira de Souza, João Pedro Rocha Pontes et al.· Molecular Biology Reports· 0 citations
Background Zinc Finger Protein 695 (ZNF695) has been reported as a prognostic indicator in several cancers; however, its clinical implications and functional contributions within uterine corpus endometrial carcinoma (UCEC) have not yet been elucidated. Herein, the prognostic significance of ZNF695 in UCEC and its potential involvement in immune infiltration were examined. Methods Bioinformatics analyses were conducted utilizing The Cancer Genome Atlas (TCGA) data to evaluate ZNF695 expression, its impact on survival, and patient clinicopathological features. ZNF695 protein expression and subcellular localization were validated using immunohistochemistry (IHC) on a UCEC tissue microarray. To dissect tumor heterogeneity and immune microenvironment, single-cell RNA-seq data from the Gene Expression Omnibus (GEO) were analyzed. The immune infiltration patterns were evaluated utilizing the CIBERSORT algorithm. Three prognostic nomograms were developed to assess UCEC patient survival at the 1-, 3-, and 5-year marks. Furthermore, in vitro cellular assays were conducted to validate ZNF695 expression and its biological roles in UCEC cells via siRNA knockdown. Results ZNF695 was significantly elevated in UCEC and associated with various clinicopathological features including age, body weight, menopause status, clinical stage, and histological grade. Functional enrichment analyses indicated that ZNF695 was involved in key biological functions, including endopeptidase regulator activity, estrogen signaling pathway and MYC targets. Additionally, single-cell subgroup analysis isolated different cell populations with high ZNF695 expression, underscoring its role in tumor microenvironment. Immune infiltration analyses indicated negative correlations between ZNF695 and various immunosuppressive immune cell subtypes. Elevated ZNF695 expression was strongly correlated with unfavorable clinical outcomes in UCEC. The nomograms for overall survival (OS), disease specific survival (DSS), and progression free interval (PFI) demonstrated promising predictive efficacy, with concordance indices (C-indexes) of 0.631, 0.719, and 0.787, respectively. In vitro functional assays demonstrated that siRNA-mediated ZNF695 knockdown markedly impaired the proliferation, migration, and invasion of UCEC cells, accompanied by cell-cycle arrest and altered apoptosis. Conclusion ZNF695 serves as an independent prognostic biomarker for UCEC, with its potential as a molecular marker validated experimentally. These findings emphasize the critical role of ZNF695 in regulating the immune landscape of UCEC, warranting studies to elucidate underlying molecular mechanisms and explore its clinical translational implications.
Hui-Juan Jiang, Jun-Ling Zhu, Zhang Lei et al.· Frontiers in Oncology· 0 citations
Background Prostate cancer (PCa) remains a leading malignancy among men worldwide, with inherited genetic susceptibility playing a pivotal role in its pathogenesis. Although numerous single nucleotide polymorphisms (SNPs) within immune response, inflammatory, and apoptotic pathways have been linked to PCa risk, these associations often exhibit substantial inconsistency across diverse populations. This study aimed to evaluate the association of selected polymorphisms within the RNASEL, ELAC2, MSR1, and KLK3 genes with PCa susceptibility in a Hungarian cohort. Methods This case-control study included 103 histologically confirmed prostate cancer patients and 103 healthy controls recruited at the University of Pécs Department of Urology. Genotyping of selected polymorphisms was performed by PCR and Sanger sequencing at the Department of Medical Genetics. Statistical associations were evaluated using chi-square tests, odds ratios, and logistic regression. Results A statistically nominally significant association with prostate cancer susceptibility was observed for the RNASEL rs486907 polymorphism, demonstrating a potential protective effect under the dominant model in the studied population (OR = 0.53, 95% CI: 0.30–0.92, p = 0.025). In the age-adjusted logistic regression analysis, this association remained statistically significant (OR = 0.56, 95% CI: 0.32–0.99, p = 0.046), suggesting that the observed effect was independent of age. In contrast, no statistically significant associations were identified between prostate cancer risk and the investigated polymorphisms in the KLK3, MSR1, or ELAC2 genes. Conclusion The present study demonstrated a significant association between the RNASEL rs486907 polymorphism and prostate cancer susceptibility in a Hungarian cohort, suggesting a potential protective effect of this variant. These findings support the possible role of inherited genetic factors in prostate cancer development and highlight the importance of population-specific genetic association studies. Further investigations involving larger cohorts are warranted to validate these observations.
Sebestyén Kovács, Renata Szalai, L. Baráti et al.· Pathology oncology research...· 0 citations
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