Abstract
Autophagy is a process of engulfing one's own cytoplasmic proteins or organelles and coating them into vesicles, fusing with lysosomes to form autophagic lysosomes, and degrading the contents it encapsulates. Increasing studies have shown that autophagy disorders are closely related to the occurrence of tumors. However, the prognostic role of autophagy genes in cervical cancer is still unclear. In this study, we constructed risk signatures of autophagy-related genes (ARGs) to predict the prognosis of cervical cancer. The expression profiles and clinical information of autophagy gene sets were downloaded from TCGA and GSE52903 queues as training and validation sets. The normal cervical tissue expression profile data from the UCSC XENA website (obtained from GTEx) were used as a supplement to the TCGA normal cervical tissue. Univariate COX regression analysis of 17 different autophagy genes was performed with the consensus approach. Tumor samples from TCGA were divided into six subtypes, and the clinical traits of the six subtypes had different distributions. Further absolute shrinkage and selection operator (LASSO) and multivariable COX regression yielded an autophagy genetic risk model consisting of eight genes. In the training set, the survival rate of the high-risk group was lower than that of the low-risk group (p < 0.0001). In the validation set, the AUC area of the receiver operating characteristic (ROC) curve was 0.772 for the training set and 0.889 for the verification set. We found that high and low risk scores were closely related to TNM stage (p < 0.05). The nomogram shows that the risk score combined with other indicators, such as G, T, M, and N, better predicts 1-, 3-, and 5-year survival rates. Decline curve analysis (DCA) shows that the risk model combined with other indicators produces better clinical efficacy. Immune cells with an enrichment score of 28 showed statistically significant differences related to high and low risk. GSEA enrichment analysis showed the main enrichment being in KRAS activation, genes defining epithelial and mesenchymal transition (EMT), raised in response to the low oxygen level (hypoxia) gene and NF-kB in response to TNF. These pathways are closely related to the occurrence of tumors. Our constructed autophagy risk signature may be a prognostic tool for cervical cancer.
Highlights
Cervical cancer is the most common malignancy of the female reproductive tract; it is diagnosed in millions of women each year and causes 300,000 deaths worldwide [1]
We used the Wilcoxon test to analyze the difference between 232 autophagy genes based on the limma package [11]. e cut-off value was selected as log2-fold change (FC) > 1 and an adjusted p value of
We identified the autophagy genes associated with the prognosis of cervical cancer by univariate COX regression, LASSO regression, and multivariate COX regression
Summary
Cervical cancer is the most common malignancy of the female reproductive tract; it is diagnosed in millions of women each year and causes 300,000 deaths worldwide [1]. Among women, this disease ranks fourth in mortality and morbidity [2]. Autophagy plays an important role in preventing cisplatin-induced apoptosis of cervical cancer cells, suggesting that inhibition of autophagy may improve cisplatin chemotherapy [10]. While these studies have revealed the role of autophagy in the occurrence and development of cervical cancer and its relationship with various tumor drugs, few studies have examined the prognostic role of autophagy in cervical cancer
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