Identification of an Immune-Related Prognostic Gene CLEC5A Based on Immune Microenvironment and Risk Modeling of Ovarian Cancer

Jiacheng Shen; Tingwei Liu; Jia Lv; Shaohua Xu

doi:10.3389/fcell.2021.746932

Identification of an Immune-Related Prognostic Gene CLEC5A Based on Immune Microenvironment and Risk Modeling of Ovarian Cancer

Front Cell Dev Biol. 2021 Oct 12:9:746932. doi: 10.3389/fcell.2021.746932. eCollection 2021.

Authors

Jiacheng Shen¹, Tingwei Liu¹, Jia Lv², Shaohua Xu¹

Affiliations

¹ Department of Gynecology, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai, China.
² Department of Obstetrics and Gynecology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.

Abstract

Objective: To understand the immune characteristics of the ovarian cancer (OC) microenvironment and explore the differences of immune-related molecules and cells to establish an effective risk model and identify the molecules that significantly affected the immune response of OC, to help guide the diagnosis. Methods: First, we calculate the TMEscore which reflects the immune microenvironment, and then analyze the molecular differences between patients with different immune characteristics, and determine the prognostic genes. Then, the risk model was established by least absolute shrinkage and selection operator (LASSO) analysis and combined with clinical data into a nomogram for diagnosis and prediction. Subsequently, the potential gene CLEC5A influencing the immune response of OC was identified from the prognostic genes by integrative immune-stromal analysis. The genomic alteration was explored based on copy number variant (CNV) and somatic mutation data. Results: TMEscore was a prognostic indicator of OC. The prognosis of patients with high TMEscore was better. The risk model based on immune characteristics was a reliable index to predict the prognosis of patients, and the nomogram could comprehensively evaluate the prognosis of patients. Besides, CLEC5A was closely related to the abundance of immune cells, immune response, and the expression of immune checkpoints in the OC microenvironment. OC cells with high expression of CLEC5A increased the polarization of M2 macrophages. CLEC5A expression was significantly associated with TTN and CDK12 mutations and affected the copy number of tumor progression and immune-related genes. Conclusion: The study of immune characteristics in the OC microenvironment and the risk model can reveal the factors affecting the prognosis and guide the clinical hierarchical treatment. CLEC5A can be used as a potential key gene affecting the immune microenvironment remodeling of OC, which provides a new perspective for improving the effect of OC immunotherapy.

Keywords: CLEC5A; immune microenvironment remodeling; immunotherapy; multi-omics; ovarian cancer; prognostic modeling.