Programmed cell death-index (PCDi) as a prognostic biomarker and predictor of drug sensitivity in cervical cancer: a machine learning-based analysis of mRNA signatures.

ABSTRACT

Purpose: Cervical cancer is a significant public health concern, particularly in developing countries. Despite available treatment strategies, the prognosis for patients with locally advanced cervical cancer and beyond remains poor. Therefore, an accurate prediction model that can reliably forecast prognosis is essential in clinical setting. Programmed cell death (PCD) mechanisms are diverse and play a critical role in tumor growth, survival, and metastasis, making PCD a potential reliable prognostic marker for cervical cancer. Methods: In this study, we created a novel prognostic indicator, programmed cell death-index (PCDi), based on a 10-fold cross-validation framework for comprehensive analysis of PCD-associated genes. Results: Our PCDi-based prognostic model outperformed previously published signature models, stratifying cervical cancer patients into two distinct groups with significant differences in overall survival prognosis, tumor immune features, and drug sensitivity. Higher PCDi scores were associated with poorer prognosis. The nomogram survival model integrated PCDi and clinical characteristics, demonstrating higher prognostic prediction performance. Furthermore, our study investigated the immune features of cervical cancer patients and found that those with high PCDi scores had lower infiltrating immune cells, lower potential of T cell dysfunction, and higher potential of T cell exclusion. Patients with high PCDi scores were resistant to classic chemotherapy regimens, including cisplatin, docetaxel, and paclitaxel, but showed sensitivity to the inhibitor SB505124 and Trametinib. Conclusion: Our findings suggest that PCD-related gene signature could serve as a useful biomarker to reliably predict prognosis and guide treatment decisions in cervical cancer.