Jin Xin, Chen Liwei, Zhou Ning, Ni Hong, Zu Lingling, He Jinling, Yang Lingqi, Zhu Yifan, Sun Xiaoyue, Li Xiaojiang, Xu Song
Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin, China.
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin, China.
Front Mol Biosci. 2021 Nov 26;8:711928. doi: 10.3389/fmolb.2021.711928. eCollection 2021.
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. The expression levels of 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. 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 , co-expressed genes, and tumor-infiltrating immune cells; Finally, the correlations between LRMP and immune checkpoints were analyzed using TIMER 2.0. The expression of was significantly lower in LUAD tissues and cell lines. High expression is associated with a better prognosis in patients with LUAD. 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. 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.
淋巴细胞限制性膜蛋白（LRMP）是一种与内质网相关的蛋白，在B细胞和T细胞谱系中以发育调控的方式表达。然而，LRMP在肺腺癌（LUAD）的生长、预后和免疫浸润中的作用仍不清楚。使用肿瘤免疫评估资源2.0（TIMER 2.0）和基因表达谱交互分析2（GEPIA 2）分析肿瘤组织和正常组织中mRNA的表达水平。使用人类蛋白质图谱检测LRMP蛋白表达。还进行了包括qRT-PCR、蛋白质免疫印迹和免疫组织化学染色在内的实验来研究LRMP的表达。使用GEPIA2和Kaplan-Meier plotter数据库分析LRMP的临床预后意义。为了进一步证实LRMP的潜在功能，使用基因集富集分析对数据进行分析。此外，我们还构建了过表达LRMP的质粒，并在A549细胞系中探索LRMP的作用。此外，使用肿瘤免疫单细胞枢纽研究LRMP在LUAD免疫微环境中的分布；使用TIMER和CIBERSORT研究LRMP、共表达基因和肿瘤浸润免疫细胞之间的关系；最后，使用TIMER 2.0分析LRMP与免疫检查点之间的相关性。LRMP在LUAD组织和细胞系中的表达显著降低。高LRMP表达与LUAD患者的较好预后相关。实验研究表明，LRMP过表达可降低A549细胞的增殖、迁移和侵袭，并下调多种致癌信号通路，包括p-STAT3、p-PI3K-p-AKT、p-MEK和EMT通路。基因集富集分析结果表明，免疫相关和细胞黏附通路在LRMP高表达样本中富集。LRMP及其共表达基因与各种肿瘤浸润免疫细胞及其标志物呈正相关。此外，LRMP与免疫检查点呈正相关。我们的数据表明，LRMP可能作为一种肿瘤抑制基因，并预示着较好的预后。此外，LRMP与免疫浸润相关，这可能参与LUAD的免疫治疗反应。需要进一步研究来验证这些发现。
