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

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.

Identification of necroptosis-related gene signatures for predicting the prognosis of ovarian cancer

“…Three necroptosis-related genes, CXCL10, RELB, and CASP3, were identified in the prognostic model through multiple regression analyses. CXCL10 is one of the inflammatory chemokines, and the research has shown that CXCL10 expression is crucial for ovarian cancer prognosis and TME immune characteristics 53 . Furthermore, CXCL10 was found to have an impact on angiogenesis in addition to stimulating T lymphocytes' ability to fight malignancies in the body 54 .…”

Identified S100A9 as a target for diagnosis and treatment of ulcerative colitis by bioinformatics analysis

“…However, immune cells, show anti-tumor effect against cancer cells through paracrine CXCL9, -10, -11/CXCR3 axis, the autocrine CXCL9, -10, -11/CXCR3 signaling in cancer cells increases cancer cell proliferation, angiogenesis, and metastasis 38 . Studies have proved that the expression levels of CXCL10 and CXCL9 in tumor may be correlated with a poor prognosis of overall survival 39 . However, some studies also show that CXCL10 and CXCL9 may promote colonic tumorigenesis via promotes the cytokine-mediated mucosal injury and inflammation response 40 .…”

RB1 Is an Immune-Related Prognostic Biomarker for Ovarian Cancer

“…There is increasing evidence which indicates that OC is an immunogenic tumor with spontaneous antitumor immune responses (12)(13)(14). Immune-related prognostic biomarkers have been reported in various studies, while some biomarkers lack experimental validation (15)(16)(17). Therefore, it is of great importance to identify a reliable and immune-related tumor marker by experimental validation.…”