Abstract
BackgroundChemokines 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.MethodsIn 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.ResultsWe 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.ConclusionsThis 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.
Highlights
Ovarian cancer is one of the most lethal gynecological tumors with complex mechanisms, and more than 295,000 new cases and 184,000 deaths were estimated to be reported in 2018 (Longacre et al, 2016; Bray et al, 2018)
The patients in different cohorts were stratified according to CXCL10 and CXCL9 expression-related overall survival (OS), and the cutoff value was determined by the survminer package
In four independent cohorts, we found that a lower CXCL10 expression was significantly associated with poorer prognosis [standard cohort HR range: 0.69]
Summary
Chemokines are implicated in tumor microenvironment (TME) cell infiltration. Development of ovarian cancer involves heterologous cells together with the adjacent microenvironment. Our understanding of the chemokine-related TME characteristics in ovarian cancer remains obscure
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