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CLEC10A is a prognostic biomarker and correlated with clinical pathologic features and immune infiltrates in lung adenocarcinoma.

ABSTRACT: CLEC10A, (C-type lectin domain family 10, member A), as the member of C-type lectin receptors (CLRs), plays a vital role in modulating innate immunity and adaptive immunity and has shown great potential as an immunotherapy target for cancers. However, there is no functional research of CLEC10A in prognostic risk, immunotherapy or any other treatment of lung adenocarcinoma (LUAD). We performed bioinformatics analysis on LUAD data downloaded from TCGA (The Cancer Genome Atlas) and GEO (Gene Expression Omnibus), and jointly analysed with online databases such as HPA, LinkedOmics, TIMER, ESTIMATE and TISIDB. We found that lower expression of CLEC10A was accompanied with worse outcomes of LUAD patients. Moreover, CLEC10A expression was significantly correlated with a variety of the tumour-infiltrating immune cells (TIICs). As a promising prognosis predictor and potential immunotherapy target, the potential influence and mechanisms of CLEC10A in LUAD deserve further exploring.

SUBMITTER: He M

PROVIDER: S-EPMC8034442 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature

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CLEC10A is a prognostic biomarker and correlated with clinical pathologic features and immune infiltrates in lung adenocarcinoma.

He Min M Han Ying Y Cai Changjing C Liu Ping P Chen Yihong Y Shen Hong H Xu Xingyuan X Zeng Shan S

Journal of cellular and molecular medicine 20210302 7

CLEC10A, (C-type lectin domain family 10, member A), as the member of C-type lectin receptors (CLRs), plays a vital role in modulating innate immunity and adaptive immunity and has shown great potential as an immunotherapy target for cancers. However, there is no functional research of CLEC10A in prognostic risk, immunotherapy or any other treatment of lung adenocarcinoma (LUAD). We performed bioinformatics analysis on LUAD data downloaded from TCGA (The Cancer Genome Atlas) and GEO (Gene Expres ...[more]

PMID: 33655701

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Project description:DCUN1D5 is up-regulated and promotes tumor progression in many cancers such as laryngeal squamous cell carcinoma and breast cancer, but the expression of DCUN1D5 in lung adenocarcinoma and its molecular mechanism are not clear. The differences of DCUN1D5 expression between lung adenocarcinoma and normal tissues were compared by TCGA, GEO and UALCAN databases, and the relationship between DCUN1D5 expression and clinicopathological features of patients was analyzed. The diagnostic and prognostic value of DCUN1D5 in patients with LUAD was analyzed by TCGA, GEPIA and Kaplan-Meier Plotter database. nomogram was constructed to predict the survival probability of patients. The GO, KEGG and GSEA enrichment analysis of DCUN1D5 co-expression genes were completed by R software. R software and GEPIA2 database were used to analyze the relationship between DCUN1D5 expression level and glycolysis-related genes and immune cell infiltration in patients with LUAD. The effects of interfering DCUN1D5 on the biological function and glycolysis level of lung adenocarcinoma cells were evaluated in vitro. The effect of down-regulation of DCUN1D5 on tumor formation in nude mice was studied in animal experiments. The expression of DCUN1D5 was increased in many kinds of tumors, and the expression in lung adenocarcinoma was significantly higher than that in normal tissues. The expression of DCUN1D5 was significantly correlated with TNM and pathological stage. DCUNN1D5 can play a diagnostic role in patients with LUAD and the prognosis of patients with high expression of DCUN1D5 is poor. Functional enrichment of DCUN1D5 co-expression genes involves a variety of biological processes. There is a strong correlation between DCUN1D5 and most glycolysis related genes. In addition, DCUN1D5 also affects tumor immune cell infiltration. In vitro experiments showed that the ability of cell proliferation, migration, invasion and glycolysis were significantly decreased and the ability of apoptosis was enhanced after down-regulation of DCUN1D5. Animal experiments showed that the tumor weight of nude mice decreased significantly after down-regulation of DCUN1D5. DCUN1D5 can be used as a biomarker for diagnosis and prognosis in lung adenocarcinoma. Down-regulation of DCUN1D5 can significantly affect the biological behavior of lung adenocarcinoma cells, which may be related to glycolysis and immune cell infiltration.

Project description:BackgroundThe tumor microenvironment plays an important role in the occurrence and development of tumors. However, there are gaps in understanding the molecular and cellular interactions between tumor cells and the immune tumor microenvironment (TME). The aim of this study was to identify a novel gene that played an important role in the tumor microenvironment of lung adenocarcinoma (LUAD).MethodsThe gene expression profile and clinical data for LUAD were downloaded from TCGA database. First, we used the ESTIMATE algorithm to evaluate the immune and stromal scores accordingly. Also, we analyzed differentially expressed immune-related genes (IRGs) in the high and low immune/stromal score groups. Then, we used the protein-protein interaction network (PPI network) and a univariate Cox regression analysis to identify the hub gene. After that, we analyzed the relationship between CSF2RB expression and TNM stage/prognosis. Furthermore, gene set enrichment analysis (GSEA) was used to analyze the pathway regulated by CSF2RB and the Pearson correlation analysis method was used to analyze the correlation between the CSF2RB and immune cells. Finally, we used Western blot, real-time quantitative PCR (RT-qPCR), and immunohistochemistry (IHC) to validate CSF2RB expression in cancer and para-cancerous tissues.ResultsWe identified that CSF2RB played an important role in the tumor microenvironment of LUAD. The expression of CSF2RB in tumor tissues was lower than that in normal tissues. Furthermore, the Kaplan-Meier plotter showed that a low CSF2RB expression was associated with poor survival and multivariate COX regression analysis revealed that the CSF2RB gene was an independent risk factor for prognosis, independent of whether patients received chemotherapy or radiotherapy. More importantly, a high expression of CSF2RB was related to early T, N, and clinical stages. GSEA analysis revealed that CSF2RB associated with diverse immune-related pathways, including T-cell receptor signaling pathway, Toll-like receptor signaling pathway, and B-cell receptor signaling pathway. CSF2RB expression levels were also positively related with the levels of infiltrating CD4+ T cells, macrophages, NK cells, and monocytes in LUAD. Finally, tumor tissues from LUAD patients were used for the assessment of CSF2RB expression. It was significantly lower in tumor sites than in adjacent normal tissues, which was consistent with data analysis.ConclusionCSF2RB effectively predicted the prognosis of patients with lung adenocarcinoma which could also be a potential target for cancer treatment and prevention. However, further studies are required to elucidate the function and regulatory mechanisms of CSF2RB and to develop some novel treatment strategies.

Dataset Information

CLEC10A is a prognostic biomarker and correlated with clinical pathologic features and immune infiltrates in lung adenocarcinoma.

Publications

CLEC10A is a prognostic biomarker and correlated with clinical pathologic features and immune infiltrates in lung adenocarcinoma.

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