Molecular Determinants of Treatment Resistance in Cervical Cancer: A Systematic Review and Integrative Bioinformatic Analysis of Publicly Available Datasets

Résumé fourni par la source

Treatment resistance remains a major challenge in cervical cancer management, particularly among patients undergoing chemoradiotherapy.Despite increasing knowledge of resistance-associated molecular pathways, clinically validated biomarkers capable of predicting treatment outcomes remain limited.This study combined a systematic review of clinical and preclinical studies with an integrative bioinformatic analysis of publicly available transcriptomic datasets.Gene expression profiles from cervical cancer models exposed to chemotherapeutic agents and epigenetic modulators were analyzed to identify treatment-response-associated transcriptional signatures.Candidate genes were subsequently evaluated in clinical datasets comprising normal cervical tissue, cervical intraepithelial neoplasia, and invasive cervical cancer.Functional enrichment analysis, protein-protein interaction network construction, and survival analyses were performed to assess biological relevance.A total of 38 genes demonstrated concordant expression changes across independent treatment conditions.Clinical evaluation revealed progressive dysregulation of several candidates during cervical neoplastic progression and invasive disease development.Functional analyses indicated enrichment of pathways related to extracellular matrix organization, metabolic regulation, and p53-associated signaling.Network analysis identified lumican (LUM) as a candidate gene occupying a relatively high connectivity within the constructed interaction network.No statistically significant association between LUM expression and overall survival was observed.This integrative approach identified reproducible treatment-response-associated transcriptional signatures that may participate in biological processes relevant to therapeutic adaptation in cervical cancer.LUM emerged as a prioritized candidate for future investigation.However, its biological and clinical significance remains exploratory and requires validation in independent treatment-annotated cohorts and functional studies.

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