Identification of hub genes and potential molecular mechanisms of tumor immune microenvironment-related radiotherapy sensitivity in locally advanced cervical cancer.

Abstract

Cervical cancer remains the most prevalent malignancy of the female reproductive system; however, the five-year survival rate has not improved substantially over recent decades. This persistent challenge highlights the critical need to elucidate mechanisms underlying treatment sensitivity and investigate synergistic effects of multimodal therapies to overcome clinical therapeutic bottlenecks. By conducting a comprehensive analysis of The Cancer Genome Atlas (TCGA) database, this study identified a hub gene network associated with radiotherapy sensitivity in cervical cancer. In addition to developing a personalized treatment prediction model, we preliminarily characterized these hub genes through several key dimensions: molecular regulatory, biological functions, tumor microenvironment infiltration patterns, and immune relevance. Notably, this work is the first to reveal that hub genes such as DDX58 probably orchestrate a tripartite regulatory mechanism-mediated by immune microenvironment factors-that concurrently influences sensitivity to radiotherapy, chemotherapy, and immunotherapy. Through a series of analyses, we speculate that these hub genes can serve not only as combined biomarkers for predicting responses to multiple therapies but also as novel molecular targets for the development of synergistic treatment strategies via their mediated immune microenvironment interactions. These findings provide a new translational research direction for overcoming therapeutic resistance in cervical cancer.