LRMP Associates With Immune Infiltrates and Acts as a Prognostic Biomarker in Lung Adenocarcinoma

Background: Lymphoid-restricted membrane protein (LRMP) is an endoplasmic reticulum-associated protein that is expressed in a developmentally regulated manner in both B and T cell lineages. However, the role of LRMP in the growth, prognosis and immune infiltration in lung adenocarcinoma (LUAD) remai...

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Autores principales: Xin Jin, Liwei Chen, Ning Zhou, Hong Ni, Lingling Zu, Jinling He, Lingqi Yang, Yifan Zhu, Xiaoyue Sun, Xiaojiang Li, Song Xu
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Publicado: Frontiers Media S.A. 2021
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spelling oai:doaj.org-article:649777577b924a01865b4150816dffac2021-12-01T07:10:07ZLRMP Associates With Immune Infiltrates and Acts as a Prognostic Biomarker in Lung Adenocarcinoma2296-889X10.3389/fmolb.2021.711928https://doaj.org/article/649777577b924a01865b4150816dffac2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmolb.2021.711928/fullhttps://doaj.org/toc/2296-889XBackground: Lymphoid-restricted membrane protein (LRMP) is an endoplasmic reticulum-associated protein that is expressed in a developmentally regulated manner in both B and T cell lineages. However, the role of LRMP in the growth, prognosis and immune infiltration in lung adenocarcinoma (LUAD) remains unclear.Method: The expression levels of LRMP mRNA in tumor and normal tissues were analyzed using Tumor Immune Estimation Resource 2.0 (TIMER 2.0) and Gene Expression Profiling Interactive Analysis 2 (GEPIA 2). LRMP protein expression was examined using the Human Protein Atlas. In vitro experiments, including qRT-PCR Western blot and immunohistochemistry staining were also performed to investigate LRMP expression. GEPIA2 and Kaplan-Meier plotter databases were used to analyze the clinical prognostic significance of LRMP. To further confirm the underlying function of LRMP, the data were analyzed using gene set enrichment analysis. Moreover, we also constructed plasmids to overexpress LRMP and explored the effect of LRMP in A549 cell line. Additionally, Tumor Immune single-cell Hub was used to investigate the distribution of LRMP in the LUAD immune microenvironment; TIMER and CIBERSORT were used to investigate the relationships among LRMP, LRMP co-expressed genes, and tumor-infiltrating immune cells; Finally, the correlations between LRMP and immune checkpoints were analyzed using TIMER 2.0.Results: The expression of LRMP was significantly lower in LUAD tissues and cell lines. High LRMP expression is associated with a better prognosis in patients with LUAD. In vitro experimental studies demonstrated that overexpression of LRMP could decrease the proliferation, migration and invasion in A549 cells, and downregulated multiple oncogenic signaling pathways, including p-STAT3, p-PI3K-p-AKT, p-MEK and EMT pathways. GSEA results showed that immuno-related and cell adhesion pathways were enriched in samples with high LRMP expression. LRMP and its co-expressed genes were positively correlated with various tumor-infiltrating immune cells and their markers. Additionally, LRMP positively correlated with immune checkpoints.Conclusions: Our data suggest that LRMP may act as a tumor suppressor gene and indicates a better prognosis. Moreover, LRMP is associated with immune infiltrates which may be involved in immunotherapy response in LUAD. Further studies are needed to validate these findings.Xin JinXin JinLiwei ChenNing ZhouNing ZhouHong NiHong NiLingling ZuLingling ZuJinling HeJinling HeLingqi YangLingqi YangYifan ZhuYifan ZhuXiaoyue SunXiaoyue SunXiaojiang LiSong XuSong XuFrontiers Media S.A.articleLRMPlung adenocarcinomaprognosisimmune infiltrationimmune checkpoints (ICP)Biology (General)QH301-705.5ENFrontiers in Molecular Biosciences, Vol 8 (2021)
institution DOAJ
collection DOAJ
language EN
topic LRMP
lung adenocarcinoma
prognosis
immune infiltration
immune checkpoints (ICP)
Biology (General)
QH301-705.5
spellingShingle LRMP
lung adenocarcinoma
prognosis
immune infiltration
immune checkpoints (ICP)
Biology (General)
QH301-705.5
Xin Jin
Xin Jin
Liwei Chen
Ning Zhou
Ning Zhou
Hong Ni
Hong Ni
Lingling Zu
Lingling Zu
Jinling He
Jinling He
Lingqi Yang
Lingqi Yang
Yifan Zhu
Yifan Zhu
Xiaoyue Sun
Xiaoyue Sun
Xiaojiang Li
Song Xu
Song Xu
LRMP Associates With Immune Infiltrates and Acts as a Prognostic Biomarker in Lung Adenocarcinoma
description Background: Lymphoid-restricted membrane protein (LRMP) is an endoplasmic reticulum-associated protein that is expressed in a developmentally regulated manner in both B and T cell lineages. However, the role of LRMP in the growth, prognosis and immune infiltration in lung adenocarcinoma (LUAD) remains unclear.Method: The expression levels of LRMP mRNA in tumor and normal tissues were analyzed using Tumor Immune Estimation Resource 2.0 (TIMER 2.0) and Gene Expression Profiling Interactive Analysis 2 (GEPIA 2). LRMP protein expression was examined using the Human Protein Atlas. In vitro experiments, including qRT-PCR Western blot and immunohistochemistry staining were also performed to investigate LRMP expression. GEPIA2 and Kaplan-Meier plotter databases were used to analyze the clinical prognostic significance of LRMP. To further confirm the underlying function of LRMP, the data were analyzed using gene set enrichment analysis. Moreover, we also constructed plasmids to overexpress LRMP and explored the effect of LRMP in A549 cell line. Additionally, Tumor Immune single-cell Hub was used to investigate the distribution of LRMP in the LUAD immune microenvironment; TIMER and CIBERSORT were used to investigate the relationships among LRMP, LRMP co-expressed genes, and tumor-infiltrating immune cells; Finally, the correlations between LRMP and immune checkpoints were analyzed using TIMER 2.0.Results: The expression of LRMP was significantly lower in LUAD tissues and cell lines. High LRMP expression is associated with a better prognosis in patients with LUAD. In vitro experimental studies demonstrated that overexpression of LRMP could decrease the proliferation, migration and invasion in A549 cells, and downregulated multiple oncogenic signaling pathways, including p-STAT3, p-PI3K-p-AKT, p-MEK and EMT pathways. GSEA results showed that immuno-related and cell adhesion pathways were enriched in samples with high LRMP expression. LRMP and its co-expressed genes were positively correlated with various tumor-infiltrating immune cells and their markers. Additionally, LRMP positively correlated with immune checkpoints.Conclusions: Our data suggest that LRMP may act as a tumor suppressor gene and indicates a better prognosis. Moreover, LRMP is associated with immune infiltrates which may be involved in immunotherapy response in LUAD. Further studies are needed to validate these findings.
format article
author Xin Jin
Xin Jin
Liwei Chen
Ning Zhou
Ning Zhou
Hong Ni
Hong Ni
Lingling Zu
Lingling Zu
Jinling He
Jinling He
Lingqi Yang
Lingqi Yang
Yifan Zhu
Yifan Zhu
Xiaoyue Sun
Xiaoyue Sun
Xiaojiang Li
Song Xu
Song Xu
author_facet Xin Jin
Xin Jin
Liwei Chen
Ning Zhou
Ning Zhou
Hong Ni
Hong Ni
Lingling Zu
Lingling Zu
Jinling He
Jinling He
Lingqi Yang
Lingqi Yang
Yifan Zhu
Yifan Zhu
Xiaoyue Sun
Xiaoyue Sun
Xiaojiang Li
Song Xu
Song Xu
author_sort Xin Jin
title LRMP Associates With Immune Infiltrates and Acts as a Prognostic Biomarker in Lung Adenocarcinoma
title_short LRMP Associates With Immune Infiltrates and Acts as a Prognostic Biomarker in Lung Adenocarcinoma
title_full LRMP Associates With Immune Infiltrates and Acts as a Prognostic Biomarker in Lung Adenocarcinoma
title_fullStr LRMP Associates With Immune Infiltrates and Acts as a Prognostic Biomarker in Lung Adenocarcinoma
title_full_unstemmed LRMP Associates With Immune Infiltrates and Acts as a Prognostic Biomarker in Lung Adenocarcinoma
title_sort lrmp associates with immune infiltrates and acts as a prognostic biomarker in lung adenocarcinoma
publisher Frontiers Media S.A.
publishDate 2021
url https://doaj.org/article/649777577b924a01865b4150816dffac
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