Abstract
Cervical cancer is one of the most common female malignancy that occurs worldwide and is reported to cause over 300,000 deaths in 2018. Autophagy controls the survival and death of cancerous cells by regulating the degradation process of cytoplasm and cellular organelle. In the present study, the differentially expressed autophagy-related genes (ARGs) between healthy and cancerous cervical tissues (squamous cell neoplasms) were obtained using data from GTEx and The Cancer Genome Atlas (TCGA) database. The functionalities of the differentially expressed ARGs were analyzed using Gene Ontology (GO) as well as the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Next, we conducted univariate Cox regression assay and obtained 12 ARGs that were associated with the prognosis of cervical cancer patients. We carried out a multivariate Cox regression analysis and developed six ARG-related prognostic signature for the survival prediction of patients with squamous cell cervical cancer (Risk score = − 0.63*ATG3–0.42*BCL2 + 0.85*CD46–0.38*IFNG+ 0.23*NAMPT+ 0.82*TM9SF1). Following the calculation of risk score using the signature, the patients were divided into high and low-risk groups according to the median value. Kaplan-Meier curve demonstrated that patients with a high-risk score tend to have a poor prognosis (P < 0.001). The value for area under the curves corresponding to the receiver operating characteristic (ROC) was 0.740. As observed, the expression of IFNG was negatively associated with lymph node metastasis (P = 0.026), while a high-risk score was significantly associated with increased age (P = 0.008). To further validate the prognostic signature, we carried out a permutation test and confirmed the performance of the risk score. In conclusion, our study developed six ARG-related prognostic signature for patients with squamous cell cervical cancer, which might help in improving the prognostic predictions of such patients.
Highlights
Cervical cancer is one of the challenging malignancies observed among females worldwide
These findings indicated that autophagy was tightly associated with the progression of cervical cancer, and autophagy-related genes (ARGs) could serve as promising therapeutic targets for cervical cancer patients
For Gene Ontology (GO) analysis, in the term of biological process (BP), the targeted genes were highly enriched in autophagy, intrinsic apoptotic signaling pathway, and cellular response to external stimulus
Summary
Cervical cancer is one of the challenging malignancies observed among females worldwide. Previous studies investigated the role of autophagy in cervical cancer. Zhu et al reported that autophagy-related genes (ARGs), Beclin-1, and LC3 were downregulated in the early stages of cervical cancer [7]. High expressions of Beclin-1 and LC3 were associated with poor prognosis in early-stage cervical squamous cell carcinoma. Xu et al investigated that the inhibition of autophagy could improve cisplatin chemotherapy sensitivity in HeLa cervical cancer cells [8]. These findings indicated that autophagy was tightly associated with the progression of cervical cancer, and ARGs could serve as promising therapeutic targets for cervical cancer patients
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