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CCL14 is a prognostic biomarker and correlates with immune infiltrates in hepatocellular carcinoma.

ABSTRACT: C-C motif chemokine ligand 14 (CCL14) is a chemokine promoting the activation of immune cells. However, the relationship between CCL14 expression, tumor immunity, and prognosis in Hepatocellular Carcinoma (HCC) remain unclear. CCL14 expression and its influence on tumor prognosis were analyzed by the ONCOMINE, Tumor Immune Estimation Resource (TIMER) and Kaplan-Meier plotter. The relationship between CCL14 expression and tumor immunity were analyzed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA). CCL14 expression was significantly lower in several human cancers, including HCC, than in corresponding normal tissues. CCL14 expression in HCC tissues correlated with prognosis. Low CCL14 expression associated with poorer overall survival, disease-specific survival, progression-free survival, and relapse-free survival in multiple cohorts of HCC patients, particularly at early disease stages (stage 1+2 or grade 2). CCL14 showed strong correlation with tumor-infiltrating B cells, CD4+ and CD8+ T cells, macrophages, neutrophils, and dendritic cells. CCL14 expression in HCC negatively correlated with expression of several immune cell markers, including exhausted T cell markers, PD-1, TIM-3 and CTLA-4, suggesting its role in regulating tumor immunity. These findings demonstrate that CCL14 is a potential prognostic biomarker that determines cancer progression and correlated with tumor immune cells infiltration in HCC.

SUBMITTER: Gu Y

PROVIDER: S-EPMC6977663 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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CCL14 is a prognostic biomarker and correlates with immune infiltrates in hepatocellular carcinoma.

Gu Yurong Y Li Xiangyong X Bi Yanhua Y Zheng Yubao Y Wang Jialiang J Li Xiaoyan X Huang Zexuan Z Chen Lubiao L Huang Yanlin Y Huang Yuehua Y

Aging 20200112 1

C-C motif chemokine ligand 14 (CCL14) is a chemokine promoting the activation of immune cells. However, the relationship between CCL14 expression, tumor immunity, and prognosis in Hepatocellular Carcinoma (HCC) remain unclear. CCL14 expression and its influence on tumor prognosis were analyzed by the ONCOMINE, Tumor Immune Estimation Resource (TIMER) and Kaplan-Meier plotter. The relationship between CCL14 expression and tumor immunity were analyzed by TIMER and Gene Expression Profiling Interac ...[more]

PMID: 31927532

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Project description:RNF183, a member of the E3 ubiquitin ligase, has been shown to involve in carcinogenesis and proposed as one of the biomarkers in Uterine Corpus Endometrial Carcinoma (UCEC). However, no research focused on the role of RNF183 in UCEC. We analyzed the expression and immune infiltration of RNF183 in UCEC. TIMER, UALCAN, and GEPIA were used to analyze the gene expression of RNF183. We emplored Kaplan-Meier Plotter to examine the overall survival and progression-free survival of RNF183, and applied GeneMANIA to identify RNF183-related functional networks. LinkedOmics was helpful to identify the differential gene expression of RNF183, and to further analyze gene ontology and the genome pathways in the Kyoto Protocol. Finally, we used TIMER to investigate the immune infiltration of RNF183 in UCEC. Otherwise, we partly verified the results of bioinformatics analysis that RNF183 controlled ERα expression in ERα-positive Ishikawa cells dependent on its RING finger domain. We also found that ERα increased the stability of RNF183 through the post-translational mechanism. Together, patients with a high level of RNF183 harbor favorable overall and progression-free survival. High expression of RNF183 was associated with a low stage, endometrioid, and TP53 Non-Mutant status in endometrial cancer. The RNF183 expression was greater at higher expression and the tumor stage was greater at the lower level. On the side of immunization, high level of RNF183 in UCEC is negatively related to tumor purity, infiltrating levels of CD4 + T cells, neutrophils, and dendritic cells. Besides, the expression of RNF183 in UCEC is significantly correlated with the expression of several immune cell markers, including B cell, M1 macrophage marker, M2 Macrophage, Dendritic cell, Th1 markers, Th2 markers, Treg markers, and T cell exhaustion markers, indicating its role in regulating tumor immunity. These results suggested that RNF183 may be considered as a novel prognostic factor in endometrial cancer and an early diagnostic indicator for patients with UCEC.

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Dataset Information

CCL14 is a prognostic biomarker and correlates with immune infiltrates in hepatocellular carcinoma.

Publications

CCL14 is a prognostic biomarker and correlates with immune infiltrates in hepatocellular carcinoma.

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