Cargando…
Downregulated Expression of CLEC9A as Novel Biomarkers for Lung Adenocarcinoma
PURPOSE: Abnormal CLEC9A expression is concerned with carcinogenesis. However, the role of CLEC9A in lung adenocarcinoma (LUAD) remains unknown. The goal of this study was to reveal the role of CLEC9A in LUAD based on bioinformatics and cellular functional experiments. MATERIALS AND METHODS: Data av...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489846/ https://www.ncbi.nlm.nih.gov/pubmed/34616670 http://dx.doi.org/10.3389/fonc.2021.682814 |
_version_ | 1784578410479091712 |
---|---|
author | Miao, Fang Lou, Zhiguo Ji, Shuhua Wang, Dan Sun, Yaolan Liu, Huan Yang, Chenggang |
author_facet | Miao, Fang Lou, Zhiguo Ji, Shuhua Wang, Dan Sun, Yaolan Liu, Huan Yang, Chenggang |
author_sort | Miao, Fang |
collection | PubMed |
description | PURPOSE: Abnormal CLEC9A expression is concerned with carcinogenesis. However, the role of CLEC9A in lung adenocarcinoma (LUAD) remains unknown. The goal of this study was to reveal the role of CLEC9A in LUAD based on bioinformatics and cellular functional experiments. MATERIALS AND METHODS: Data available from The Cancer Genome Atlas (TCGA) were employed to study CLEC9A expression and mutations in LUAD. Expression and alterations of CLEC9A were analyzed using UALCAN and cBioPortal, respectively. Kaplan–Meier analysis was used to analyze the effect of CLEC9A on the survival of LUAD. Protein–protein interaction (PPI) network was built using GeneMANIA analysis. The similar genes of CLEC9A were obtained using GEPIA analysis, while co-expression genes correlated with CLEC9A were identified using LinkedOmics analysis. The effects of CLEC9A expression on immune cell infiltration was assessed. The effect of CLEC9A on the proliferation, apoptosis, cell cycle distribution, and invasion of human LUAD cells was detected in the LUAD cell line. RESULTS: CLEC9A was downregulated and the CLEC9A gene was often altered in LUAD. The survival of LUAD patients was correlated with the expression level of CLEC9A. The similar genes of CLEC9A were linked to functional networks involving positive regulation of interleukin-12 production, plasma membrane and CD40 receptor binding, primary immunodeficiency, intestinal immune network for IgA production, and cell adhesion molecules pathways. Cell cycle, apoptosis, EMT, and RAS/MAPK were significantly enriched pathways in positive and negative correlation genes with CLEC9A. A difference in the immune infiltration level of immune cell between the high and low CLEC9A expression groups was observed. Somatic cell copy number alternations (CNAs) of the CLEC9A, including arm-level gain and arm-level deletion, observably changed the infiltration levels of B cells, CD4+ T cells, macrophages, and neutrophils in LUAD. Except for LAG3, the expression of CD274, CTLA4, PDCD1, and TIGIT was positively correlated with the expression level of CLEC9A. After transfection, overexpression and knockdown of CLEC9A could affect the proliferation, apoptosis, cell cycle distribution, and invasion of LUAD cells. CONCLUSION: CLEC9A is associated with prognosis and tumor immune microenvironment of LUAD, suggesting that CLEC9A may be considered as a novel biomarker for LUAD. |
format | Online Article Text |
id | pubmed-8489846 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84898462021-10-05 Downregulated Expression of CLEC9A as Novel Biomarkers for Lung Adenocarcinoma Miao, Fang Lou, Zhiguo Ji, Shuhua Wang, Dan Sun, Yaolan Liu, Huan Yang, Chenggang Front Oncol Oncology PURPOSE: Abnormal CLEC9A expression is concerned with carcinogenesis. However, the role of CLEC9A in lung adenocarcinoma (LUAD) remains unknown. The goal of this study was to reveal the role of CLEC9A in LUAD based on bioinformatics and cellular functional experiments. MATERIALS AND METHODS: Data available from The Cancer Genome Atlas (TCGA) were employed to study CLEC9A expression and mutations in LUAD. Expression and alterations of CLEC9A were analyzed using UALCAN and cBioPortal, respectively. Kaplan–Meier analysis was used to analyze the effect of CLEC9A on the survival of LUAD. Protein–protein interaction (PPI) network was built using GeneMANIA analysis. The similar genes of CLEC9A were obtained using GEPIA analysis, while co-expression genes correlated with CLEC9A were identified using LinkedOmics analysis. The effects of CLEC9A expression on immune cell infiltration was assessed. The effect of CLEC9A on the proliferation, apoptosis, cell cycle distribution, and invasion of human LUAD cells was detected in the LUAD cell line. RESULTS: CLEC9A was downregulated and the CLEC9A gene was often altered in LUAD. The survival of LUAD patients was correlated with the expression level of CLEC9A. The similar genes of CLEC9A were linked to functional networks involving positive regulation of interleukin-12 production, plasma membrane and CD40 receptor binding, primary immunodeficiency, intestinal immune network for IgA production, and cell adhesion molecules pathways. Cell cycle, apoptosis, EMT, and RAS/MAPK were significantly enriched pathways in positive and negative correlation genes with CLEC9A. A difference in the immune infiltration level of immune cell between the high and low CLEC9A expression groups was observed. Somatic cell copy number alternations (CNAs) of the CLEC9A, including arm-level gain and arm-level deletion, observably changed the infiltration levels of B cells, CD4+ T cells, macrophages, and neutrophils in LUAD. Except for LAG3, the expression of CD274, CTLA4, PDCD1, and TIGIT was positively correlated with the expression level of CLEC9A. After transfection, overexpression and knockdown of CLEC9A could affect the proliferation, apoptosis, cell cycle distribution, and invasion of LUAD cells. CONCLUSION: CLEC9A is associated with prognosis and tumor immune microenvironment of LUAD, suggesting that CLEC9A may be considered as a novel biomarker for LUAD. Frontiers Media S.A. 2021-09-20 /pmc/articles/PMC8489846/ /pubmed/34616670 http://dx.doi.org/10.3389/fonc.2021.682814 Text en Copyright © 2021 Miao, Lou, Ji, Wang, Sun, Liu and Yang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Miao, Fang Lou, Zhiguo Ji, Shuhua Wang, Dan Sun, Yaolan Liu, Huan Yang, Chenggang Downregulated Expression of CLEC9A as Novel Biomarkers for Lung Adenocarcinoma |
title | Downregulated Expression of CLEC9A as Novel Biomarkers for Lung Adenocarcinoma |
title_full | Downregulated Expression of CLEC9A as Novel Biomarkers for Lung Adenocarcinoma |
title_fullStr | Downregulated Expression of CLEC9A as Novel Biomarkers for Lung Adenocarcinoma |
title_full_unstemmed | Downregulated Expression of CLEC9A as Novel Biomarkers for Lung Adenocarcinoma |
title_short | Downregulated Expression of CLEC9A as Novel Biomarkers for Lung Adenocarcinoma |
title_sort | downregulated expression of clec9a as novel biomarkers for lung adenocarcinoma |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8489846/ https://www.ncbi.nlm.nih.gov/pubmed/34616670 http://dx.doi.org/10.3389/fonc.2021.682814 |
work_keys_str_mv | AT miaofang downregulatedexpressionofclec9aasnovelbiomarkersforlungadenocarcinoma AT louzhiguo downregulatedexpressionofclec9aasnovelbiomarkersforlungadenocarcinoma AT jishuhua downregulatedexpressionofclec9aasnovelbiomarkersforlungadenocarcinoma AT wangdan downregulatedexpressionofclec9aasnovelbiomarkersforlungadenocarcinoma AT sunyaolan downregulatedexpressionofclec9aasnovelbiomarkersforlungadenocarcinoma AT liuhuan downregulatedexpressionofclec9aasnovelbiomarkersforlungadenocarcinoma AT yangchenggang downregulatedexpressionofclec9aasnovelbiomarkersforlungadenocarcinoma |