Landscape of Immune Microenvironment in Epithelial Ovarian Cancer and Establishing Risk Model by Machine Learning

Author:

Liu Shi-yi1ORCID,Zhu Rong-hui1,Wang Zi-tao1,Tan Wei1,Zhang Li1,Wang Yan-qing1,Dai Fang-fang1,Yuan Meng-qin1,Zheng Ya-jing1,Yang Dong-yong1,Wang Fei-yan2,Xian Shu1,He Juan1,Zhang Yu-wei1,Wu Ma-li1,Deng Zhi-min1,Hu Min1,Cheng Yan-xiang1ORCID,Liu Ye-qiang3ORCID

Affiliation:

1. Department of Obstetrics and Gynecology, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, China

2. Shanghai Skin Disease Clinical College of Anhui Medical University, Shanghai Skin Disease Hospital, Shanghai 200443, China

3. Department of Dermatopathology, Shanghai Skin Disease Hospital, Tongji University School of Medicine,, Shanghai 200071, Shanghai, China

Abstract

Background. Epithelial ovarian cancer (EOC) is an extremely lethal gynecological malignancy and has the potential to benefit from the immune checkpoint blockade (ICB) therapy, whose efficacy highly depends on the complex tumor microenvironment (TME). Method and Result. We comprehensively analyze the landscape of TME and its prognostic value through immune infiltration analysis, somatic mutation analysis, and survival analysis. The results showed that high infiltration of immune cells predicts favorable clinical outcomes in EOC. Then, the detailed TME landscape of the EOC had been investigated through “xCell” algorithm, Gene set variation analysis (GSVA), cytokines expression analysis, and correlation analysis. It is observed that EOC patients with high infiltrating immune cells have an antitumor phenotype and are highly correlated with immune checkpoints. We further found that dendritic cells (DCs) may play a dominant role in promoting the infiltration of immune cells into TME and forming an antitumor immune phenotype. Finally, we conducted machine-learning Lasso regression, support vector machines (SVMs), and random forest, identifying six DC-related prognostic genes (CXCL9, VSIG4, ALOX5AP, TGFBI, UBD, and CXCL11). And DC-related risk stratify model had been well established and validated. Conclusion. High infiltration of immune cells predicted a better outcome and an antitumor phenotype in EOC, and the DCs might play a dominant role in the initiation of antitumor immune cells. The well-established risk model can be used for prognostic prediction in EOC.

Funder

National Natural Science Foundation of China

Publisher

Hindawi Limited

Subject

Oncology

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