Identification of an autophagy-related gene signature for survival prediction in patients with cervical cancer

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Identification of an autophagy-related gene signature for survival prediction in patients with cervical cancer Hengyu Chen1,2,3† , Qingchun Deng3†, Wenwen Wang4, Huishan Tao4* and Ying Gao4*

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.

Introduction Cervical cancer is one of the challenging malignancies observed among females worldwide. Over 300,000 women die of cervical cancer each year, and approximately 90% of them are from low- to middle-income countries [1]. Infection of high-risk human papillomavirus (HPV) is one of the main reasons for cervical cancer, * Correspondence: [email protected]; [email protected] † Hengyu Chen and Qingchun Deng equal contribution and co-first authors. 4 Department of Gynecology and Obstetrics, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China Full list of author information is available at the end of the article

although HPV infection cannot fully elucidate the occurrence of cervical cancer [2]. Five-year overall survival (OS) of locally advanced cervical cancer is around 70% following chemotherapy [3]. Surviv