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CD163 as a novel target gene of STAT3 is a potential therapeutic target for gastric cancer.

ABSTRACT: CD163 is a member of the scavenger receptor cysteine-rich superfamily, and has been widely used to identify M2 type macrophage. However, the expression of CD163 in gastric cancer and its regulatory mechanism are still unclear. Here we show that CD163 is elevated in gastric cancer tissues. High expression of CD163 is a potential indicator to evaluate the status of tumor associated macrophages (TAMs), regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and cancer associated fibroblasts (Cafs). Besides, more CD163 positive macrophages and CD163 expressing gastric cancer cells are associated with tumor invasion and poor prognosis. Knocking-down CD163 in cancer cells could inhibit tumor growth in vivo. We also find various immune molecules which are correlated with CD163 in gastric cancer tissues and cell lines have positive staining in the cancer cells of clinical sample. Finally, we confirm CD163 is a novel target gene of STAT3 (signal transducer and activator of transcription 3) in gastric cancer. Our data indicate that CD163 may be a potential poor prognostic marker and therapeutic target for gastric cancer.

SUBMITTER: Cheng Z

PROVIDER: S-EPMC5675630 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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CD163 as a novel target gene of STAT3 is a potential therapeutic target for gastric cancer.

Cheng Zhenguo Z Zhang Danhua D Gong Baocheng B Wang Pengliang P Liu Funan F

Oncotarget 20170814 50

CD163 is a member of the scavenger receptor cysteine-rich superfamily, and has been widely used to identify M2 type macrophage. However, the expression of CD163 in gastric cancer and its regulatory mechanism are still unclear. Here we show that CD163 is elevated in gastric cancer tissues. High expression of CD163 is a potential indicator to evaluate the status of tumor associated macrophages (TAMs), regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs) and cancer associated fibrob ...[more]

PMID: 29152078

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Project description:BackgroundIt has been reported that the human family with sequence similarity 198, member B (Fam198b) play an important role in the occurrence and development of various cancers. Nevertheless, its function in gastric cancer is not completely clear. Hereby, we investigated the function and prognostic value of Fam198b in gastric cancer and further validated the results in gastric cancer through a series of in vitro experiments.MethodsWe used R software and online bioinformatics analysis tools-GEPIA2, TIMER2, Kaplan-Meier plotter, cBioPortal, TISIDB COSMIC, and STRING to study the characteristics and functions of Fam198b in GC, such as aberrant expression, prognostic value, genomic alterations, immune microenvironment, anticancer drug sensitivity, and related signaling pathways. In addition, in vitro experiments such as immunohistochemistry (IHC), cell function experiments, and signaling pathway experiments were performed to validate the key conclusions.ResultFam198b is obviously highly expressed in gastric cancer, and its expression is intensively correlated with tumor prognosis. The etiology of abnormal Fam198b expression was superficially investigated and validated by associating genomic alterations and the immune microenvironment. Furthermore, Fam198b is intensively correlated with the sensitivity of multiple antitumor drugs. It was demonstrated by functional enrichment analysis that Fam198b was linked to myogenesis, angiogenesis, epithelial mesenchymal transition and cytokine binding. It was observed in vitro experiments that knockdown Fam198b could significantly inhibit tumor cell proliferation and migration. These results were reversed when Fam198b was overexpressed. It was validated by signaling pathway experiments that Fam198b promoted gastric cancer progression by up-regulating the PI3K/AKT/BCL-2 signaling pathway.ConclusionAs a novel biomarker to predict GC prognosis and tumor progression, Fam198b is a promising therapeutic target to reverse tumor progression.

Dataset Information

CD163 as a novel target gene of STAT3 is a potential therapeutic target for gastric cancer.

Publications

CD163 as a novel target gene of STAT3 is a potential therapeutic target for gastric cancer.

Similar Datasets

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