A novel prognostic index based on autophagy-related genes-the Achilles' heel of cervical squamous cell carcinoma

Despite sustained advances in the diagnosis and treatment of cervical squamous cell carcinoma (CESC), patients with advanced or recurrent CESC are prone to a poor prognosis. Accumulating evidence suggests that autophagy-related genes (ARGs) are prominent indicators of CESC prognosis. Transcriptomic and clinical data of CESC patients were obtained from The Cancer Genome Atlas (TCGA) database to calculate an autophagy-related gene prognostic index (API) based on the hub genes using a least absolute shrinkage and selection operator (Lasso) -Cox regression model. Its efficacy in predicting the overall survival (OS) and immunotherapeutic responses of CESC patients was assessed. Three autophagy-related genes, B cell leukemia/lymphoma 2 (BCL2) and tumor protein p73 (TP73), were independent prognostic factors of CESC and were used to obtain API. Patients with high API showed better OS, along with enhanced infiltration of (cluster of differentiation 8+) CD8+ T and Treg cells, inhibition of activated natural killer (NK) cells, and activation of dendritic cell infiltration in CESC tissues. As compared to those with low API, patients with a high API showed enhanced expressions of immune checkpoints, including programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte associated protein 4 (CTLA4), and lower half maximal inhibitory concentration (IC50) values for common chemotherapy agents, including paclitaxel and cisplatin. Collectively, low expression of ARGs, namely BCL2 and TP73, may be the Achilles' heel for CESC. API could accurately predict the prognosis and efficacy of immunotherapy and chemotherapy for CESC patients.