TLN1 as a potential prognostic biomarker for cervical cancer patients undergoing cisplatin treatment

Cervical cancer is the fourth most prevalent cancer among women globally, with a high incidence in low- and middle-income countries. Despite advances in screening, the increasing morbidity and mortality rates underscore the need for novel diagnostic and prognostic biomarkers. Cisplatin is a cornerstone of cervical cancer treatment, but resistance to cisplatin remains a significant challenge. This study investigates the role of disulfidptosis-related genes (DRGs) in cervical cancer prognosis and response to cisplatin chemotherapy, aiming to identify potential biomarkers to inform treatment strategies. Bioinformatics approaches were used to identify DRGs associated with cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) using data from The Cancer Genome Atlas (TCGA) and the GTEx Genotype-Tissue Expression (GTEx) databases. Gene expression and methylation levels of 24 DRGs were analyzed in cervical cancer and normal tissues, and their correlation with survival outcomes in cisplatin-treated patients was examined. Immune infiltration analysis was performed using the TIMER Tumor Immune Estimation Resource (TIMER) 2.0 platform. Enrichment analysis was conducted using the STRING and Metascape databases to explore the biological relevance of DRGs in cervical cancer. The expression analysis revealed significant differential expression of DRGs in cervical cancer, with RPN1 and CD2AP overexpressed, and FLNA, TLN1, and MYH10 underexpressed compared to normal tissues. Notably, methylation analysis indicated lower methylation of MYH10 and CD2AP in cervical cancer, suggesting their potential as early biomarkers. High expression of TLN1 was associated with poorer survival outcomes in cisplatin-treated patients (time-dependent Area Under the Curve = 0.658 at 3 years). Furthermore, drug sensitivity analysis using the Genomics of Drug Sensitivity in Cancer (GDSC) database showed a positive correlation trend between TLN1 expression and cisplatin Half-Maximal Inhibitory Concentration (IC50) in cervical cancer cell lines (Pearson’s r = 0.488, p = 0.090). Immune infiltration analysis showed a correlation between TLN1 expression and the presence of B cells, CD4 + T cells, neutrophils, and dendritic cells in the tumor microenvironment, which may impact tumor progression. Additionally, TLN1 was linked to key pathways involved in adhesion, cytoskeletal regulation, and immune response. This study highlights the importance of DRGs in cervical cancer prognosis and cisplatin chemotherapy response. Our findings suggest that high TLN1 expression may serve as a potential prognostic biomarker for poor prognosis in cervical cancer patients treated with cisplatin, potentially linked to cytoskeletal regulation and immune cell infiltration. These hypothesis-generating results warrant further investigation in larger independent cohorts to validate the prognostic value of TLN1 and explore its functional relevance to disulfidptosis. These results offer potential insights for enhancing treatment strategies and warrant further investigation into the functional roles of DRGs in cervical cancer.