Identification of CXCL10-Relevant Tumor Microenvironment Characterization and Clinical Outcome in Ovarian Cancer

Abstract

Background: Chemokines are implicated in tumor microenvironment (TME) cell infiltration. Development of ovarian cancer involves heterologous cells together with the adjacent microenvironment. Nonetheless, our understanding of the chemokine-related TME characteristics in ovarian cancer remains obscure. Methods: In this large-scale multi-platform study of 10 microarray datasets consisting of 1,673 ovarian cancer patients, we comprehensively evaluated CXCL10 and CXCL9 expression risk classifications for predicting overall survival (OS) and TME immune characteristics. The cross-validation between a standard cohort (TCGA: The Cancer Genome Atlas) and three test cohorts (GEO: Gene-Expression Omnibus) was applied. We investigated differences in the biological functions and the underlying mechanisms between high- and low-risk classifications. Results: We identified that evaluation of CXCL10 expression could predict the tumor development, immune cell infiltration, TME signature, genetic alteration, and patient prognosis in ovarian cancer. Low-risk classification was characterized by high CXCL10 expression and prolonged prognosis, which was positively associated with specific immune cell infiltration (i.e., T cells, DCs, aDC, and Th2 cells) and TME immune-relevant signatures. Meanwhile, the high-risk classification was defined by lower CXCL10/CXCL9 expression and relevant poor prognosis and immune infiltrations. The CXCL10-based low-risk classification was also linked to antitumor biological function of specific immune gene sets, such as IL2-STAT5 signaling. Additionally, a mutational pattern featured by enrichment of C > T transition was further identified to be associated with immune cell infiltration. Conclusions: This work proposed a promising biomarker for evaluating TME immune characteristics and clinical outcomes in patients with ovarian cancer. Estimation of CXCL10 risk pattern sheds a novel insight on ovarian cancer TME immune characteristics and provides strategies for ovarian cancer immunotherapy.