Analysis of Autophagy-Related Signatures Identified Two Distinct Subtypes for Evaluating the Tumor Immune Microenvironment and Predicting Prognosis in Ovarian Cancer

Ovarian cancer (OC) is one of the most lethal gynecologic malignant tumors. The interaction between autophagy and the tumor immune microenvironment has clinical importance. Hence, it is necessary to explore reliable biomarkers associated with autophagy-related genes (ARGs) for risk stratification in...

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Main Authors: Xingyu Chen, Hua Lan, Dong He, Zhanwang Wang, Runshi Xu, Jing Yuan, Mengqing Xiao, Yao Zhang, Lian Gong, Songshu Xiao, Ke Cao
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-05-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2021.616133/full
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author Xingyu Chen
Hua Lan
Dong He
Zhanwang Wang
Runshi Xu
Jing Yuan
Mengqing Xiao
Yao Zhang
Lian Gong
Songshu Xiao
Ke Cao
author_facet Xingyu Chen
Hua Lan
Dong He
Zhanwang Wang
Runshi Xu
Jing Yuan
Mengqing Xiao
Yao Zhang
Lian Gong
Songshu Xiao
Ke Cao
author_sort Xingyu Chen
collection DOAJ
description Ovarian cancer (OC) is one of the most lethal gynecologic malignant tumors. The interaction between autophagy and the tumor immune microenvironment has clinical importance. Hence, it is necessary to explore reliable biomarkers associated with autophagy-related genes (ARGs) for risk stratification in OC. Here, we obtained ARGs from the MSigDB database and downloaded the expression profile of OC from TCGA database. The k-means unsupervised clustering method was used for clustering, and two subclasses of OC (cluster A and cluster B) were identified. SsGSEA method was used to quantify the levels of infiltration of 24 subtypes of immune cells. Metascape and GSEA were performed to reveal the differential gene enrichment in signaling pathways and cellular processes of the subtypes. We found that patients in cluster A were significantly associated with higher immune infiltration and immune-associated signaling pathways. Then, we established a risk model by LASSO Cox regression. ROC analysis and Kaplan-Meier analysis were applied for evaluating the efficiency of the risk signature, patients with low-risk got better outcomes than those with high-risk in overall survival. Finally, ULK2 and GABARAPL1 expression was further validated in clinical samples. In conclusion, Our study constructed an autophagy-related prognostic indicator, and identified two promising targets in OC.
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spelling doaj.art-fabbdbfd2b7a442fa67e2a491710f6b92022-12-21T21:27:50ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2021-05-011110.3389/fonc.2021.616133616133Analysis of Autophagy-Related Signatures Identified Two Distinct Subtypes for Evaluating the Tumor Immune Microenvironment and Predicting Prognosis in Ovarian CancerXingyu Chen0Hua Lan1Dong He2Zhanwang Wang3Runshi Xu4Jing Yuan5Mengqing Xiao6Yao Zhang7Lian Gong8Songshu Xiao9Ke Cao10Department of Oncology, Third Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Obstetrics and Gynecology, Third Xiangya Hospital of Central South University, Changsha, ChinaThe Second People’s Hospital of Hunan Province, Hunan University of Chinese Medicine, Changsha, ChinaDepartment of Oncology, Third Xiangya Hospital of Central South University, Changsha, ChinaMedical School, Hunan University of Chinese Medicine, Changsha, ChinaDepartment of Obstetrics and Gynecology, Third Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Oncology, Third Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Oncology, Third Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Oncology, Third Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Obstetrics and Gynecology, Third Xiangya Hospital of Central South University, Changsha, ChinaDepartment of Oncology, Third Xiangya Hospital of Central South University, Changsha, ChinaOvarian cancer (OC) is one of the most lethal gynecologic malignant tumors. The interaction between autophagy and the tumor immune microenvironment has clinical importance. Hence, it is necessary to explore reliable biomarkers associated with autophagy-related genes (ARGs) for risk stratification in OC. Here, we obtained ARGs from the MSigDB database and downloaded the expression profile of OC from TCGA database. The k-means unsupervised clustering method was used for clustering, and two subclasses of OC (cluster A and cluster B) were identified. SsGSEA method was used to quantify the levels of infiltration of 24 subtypes of immune cells. Metascape and GSEA were performed to reveal the differential gene enrichment in signaling pathways and cellular processes of the subtypes. We found that patients in cluster A were significantly associated with higher immune infiltration and immune-associated signaling pathways. Then, we established a risk model by LASSO Cox regression. ROC analysis and Kaplan-Meier analysis were applied for evaluating the efficiency of the risk signature, patients with low-risk got better outcomes than those with high-risk in overall survival. Finally, ULK2 and GABARAPL1 expression was further validated in clinical samples. In conclusion, Our study constructed an autophagy-related prognostic indicator, and identified two promising targets in OC.https://www.frontiersin.org/articles/10.3389/fonc.2021.616133/fullovarian cancerprognostic risk signatureautophagy-related genestumor immune microenvironmentimmunotherapy
spellingShingle Xingyu Chen
Hua Lan
Dong He
Zhanwang Wang
Runshi Xu
Jing Yuan
Mengqing Xiao
Yao Zhang
Lian Gong
Songshu Xiao
Ke Cao
Analysis of Autophagy-Related Signatures Identified Two Distinct Subtypes for Evaluating the Tumor Immune Microenvironment and Predicting Prognosis in Ovarian Cancer
Frontiers in Oncology
ovarian cancer
prognostic risk signature
autophagy-related genes
tumor immune microenvironment
immunotherapy
title Analysis of Autophagy-Related Signatures Identified Two Distinct Subtypes for Evaluating the Tumor Immune Microenvironment and Predicting Prognosis in Ovarian Cancer
title_full Analysis of Autophagy-Related Signatures Identified Two Distinct Subtypes for Evaluating the Tumor Immune Microenvironment and Predicting Prognosis in Ovarian Cancer
title_fullStr Analysis of Autophagy-Related Signatures Identified Two Distinct Subtypes for Evaluating the Tumor Immune Microenvironment and Predicting Prognosis in Ovarian Cancer
title_full_unstemmed Analysis of Autophagy-Related Signatures Identified Two Distinct Subtypes for Evaluating the Tumor Immune Microenvironment and Predicting Prognosis in Ovarian Cancer
title_short Analysis of Autophagy-Related Signatures Identified Two Distinct Subtypes for Evaluating the Tumor Immune Microenvironment and Predicting Prognosis in Ovarian Cancer
title_sort analysis of autophagy related signatures identified two distinct subtypes for evaluating the tumor immune microenvironment and predicting prognosis in ovarian cancer
topic ovarian cancer
prognostic risk signature
autophagy-related genes
tumor immune microenvironment
immunotherapy
url https://www.frontiersin.org/articles/10.3389/fonc.2021.616133/full
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