肺腺癌 ERLIN2 过表达患者的分子和免疫特征。
Molecular and Immune Characteristics for Lung Adenocarcinoma Patients With ERLIN2 Overexpression.
机构信息
Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China.
Medical School of Nantong University, Nantong, China.
出版信息
Front Immunol. 2020 Dec 7;11:568440. doi: 10.3389/fimmu.2020.568440. eCollection 2020.
BACKGROUND
Endoplasmic reticulum lipid raft-associated protein 2 (ERLIN2) is protein contained in the membrane of the endoplasmic reticulum. In lung adenocarcinoma (LUAD), the molecular function of ERLIN2 and the correlation between ERLIN2 and tumor-infiltrating immune cells have been unclear. The aim of our study was to determine the role of ERLIN2 in LUAD development to provide a better understanding of the molecular pathogenesis of this disease and identify new therapeutic targets for its treatment.
METHODS
Immunohistochemistry, Western blotting, and real-time quantitative polymerase chain reaction were used to detect protein and mRNA levels of ERLIN2 in LUAD and adjacent normal tissues. Using the A549, H1299 cell line, ERLIN2-short hairpin RNA was applied to silence ERLIN2 to determine its role in LUAD cell proliferation and invasion. Based on mRNA expression of ERLIN2 from the Cancer Genome Atlas (TCGA) database, we identified ERLIN2-related protein-coding genes and analyzed the Kyoto Encyclopedia of Genes and Genomes pathway to explore its potential biological functions and determined the correlation between ERLIN2 and tumor-infiltrating immune cells.
RESULTS
ERLIN2 was abnormally expressed in a variety of tumor tissues and is highly expressed in LUAD. This overexpression was associated with histological grade (P = 0.044), TNM stage (P = 0.01), and lymph node metastasis (P = 0.038). Patient overall survival was poorer with ERLIN2 overexpression. Downregulation of ERLIN2 inhibited LUAD cell proliferation and invasion in vitro. Based on mRNA expression of ERLIN2 from the TCGA database, 13 ERLIN2-related genes and 10 pathways were identified and showed a correlation between ERLIN2 and naive B cells and neutrophils.
CONCLUSION
ERLIN2 could serve as a potential diagnostic and prognostic biomarker for LUAD and has demonstrated to be correlated with immune infiltrates, which suggests that it may represent a new therapeutic target for LUAD.
背景
内质网脂质筏相关蛋白 2（ERLIN2）是一种位于内质网膜中的蛋白。在肺腺癌（LUAD）中，ERLIN2 的分子功能及其与肿瘤浸润免疫细胞的相关性尚不清楚。本研究旨在确定 ERLIN2 在 LUAD 发展中的作用，以便更好地了解该疾病的分子发病机制，并为其治疗确定新的治疗靶点。
方法
采用免疫组织化学、Western blot 和实时定量聚合酶链反应检测 LUAD 及相邻正常组织中 ERLIN2 的蛋白和 mRNA 水平。应用 A549、H1299 细胞系，通过 ERLIN2-short hairpin RNA 沉默 ERLIN2，以确定其在 LUAD 细胞增殖和侵袭中的作用。基于癌症基因组图谱（TCGA）数据库中 ERLIN2 的 mRNA 表达，我们鉴定了 ERLIN2 相关的蛋白编码基因，并分析了京都基因与基因组百科全书（KEGG）通路，以探讨其潜在的生物学功能，并确定 ERLIN2 与肿瘤浸润免疫细胞的相关性。
结果
ERLIN2 在多种肿瘤组织中异常表达，在 LUAD 中高表达。这种过表达与组织学分级（P=0.044）、TNM 分期（P=0.01）和淋巴结转移（P=0.038）有关。ERLIN2 过表达的患者总生存期较差。体外下调 ERLIN2 抑制 LUAD 细胞的增殖和侵袭。基于 TCGA 数据库中 ERLIN2 的 mRNA 表达，鉴定出 13 个 ERLIN2 相关基因和 10 条通路，表明 ERLIN2 与幼稚 B 细胞和中性粒细胞之间存在相关性。
结论
ERLIN2 可作为 LUAD 的潜在诊断和预后生物标志物，且与免疫浸润相关，这表明它可能是 LUAD 的一个新的治疗靶点。
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