Identification of Therapeutic Targets and Prognostic Biomarkers Among Matrix Metalloproteinases in the Ovarian Cancer Microenvironment
Identification of Therapeutic Targets and Prognostic Biomarkers Among Matrix Metalloproteinases in the Ovarian Cancer Microenvironment
Mao MeiYa, Sheng Yuehua, Ding Huiqing*, Zheng Xiaojiao and Du Yongming
ABSTRACT
Ovarian cancer (OC) is one of the most common malignances with an ever-increasing incidence and high mortality. Cross-talk between cancer cells and interstitial cells exerts significant effects on ovarian and tumor development and is modulated in part by MMPs. MMPs in the tumor microenvironment can modulate immune cell trafficking and regulate tumor cell activities, thus exerting anti-tumor immunological effects and affecting patient outcomes; however, the expression and prognostic values of MMPs in ovarian cancer have not been clarified. Oncomine, NCBI, GEPIA, cBio Portal, Gene MANIA, DAVID 6.8, Meta scape, TRRUST, Linked Omics and TIMER were utilized in this study. The transcriptional levels of MMP1/7/9/10/11/14 in OC tissues were significantly elevated while the transcriptional levels of MMP2/16/23A/23B/28 were significantly reduced. A significant correlation was found between the expression of MMP7/9/12/15/25/27 and the pathological stage of OC patients. OC patients with low transcriptional levels of MMP1/4/12/17 were associated with a significantly better prognosis. The functions of differentially expressed MMPs are primarily related to the matrix metalloproteinases signaling pathway, cell surface receptor receptor interactions, and immune response signaling pathway. Our data suggest that JUN, STAT3, ETV4, ETS1, RELA and NFKB1 are key transcription factors for MMPs, and the SRC family of tyrosine kinases (LCK, LYN, and FYN), threonine kinase (ATR and ATM), CSNK2A1,CDK2 and EGFR are MMPs targets.The various miRNA targets of differentially expressed MMPs. We found significant correlations among the expression of MMPs and the infiltration of six types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). Our results may provide novel insights for the selection of immunotherapeutic targets and prognostic biomarkers for OC.
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