Department of Gastrointestinal Surgery, the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian Province, China.
Department of Gastrointestinal Surgery, National Regional Medical Center, Binhai Campus of the First Affiliated Hospital, Fujian Medical University, Fuzhou, 350212, China.
World J Surg Oncol. 2023 Jun 28;21(1):193. doi: 10.1186/s12957-023-03070-1.
Stomach adenocarcinoma (STAD) is the most common histological type of gastric cancer (GC). Macrophages are an essential part of the tumor microenvironment. We attempted to search for potential molecular markers associated with macrophages, which might be helpful for STAD diagnosis and treatment.
Firstly, exosome in macrophages was extracted for RNA sequencing to identify differentially expressed microRNAs (miRNAs) (DEmiRNAs). Then, DEmiRNAs and differentially expressed mRNAs (DEmRNAs) were screened in the Cancer Genome Atlas (TCGA) database. The miRNAs related to macrophage M2 polarization were obtained by intersecting the DEmiRNAs obtained from the sequencing data and TCGA data. Using the Pearson correlation coefficient method, the mRNAs significantly related to macrophage M2 were screened out, followed by construction of the macrophage M2-miRNA-mRNA network. Subsequently, real-time-polymerase chain reaction (RT-PCR) and online datasets were applied to validate the expression of DEmiRNAs and DEmRNAs.
A total of 6 DEmiRNAs were identified in RNA sequencing; 59 DEmiRNAs and 1838 DEmRNAs were identified in TCGA database. Among which, a common miRNA (hsa-miR-133a-3p) associated with the M2 polarization of macrophages was identified. Fifteen common mRNAs were obtained between DEmRNAs and mRNAs targeted by DEmiRNAs. Eventually, a core macrophage M2-1 down-regulated miRNA-7 and up-regulated mRNAs network was constructed, including hsa-miR-133a-3p, SLC39A1, TTYH3, HAVCR2, TPM3, XPO1, POU2F1, and MMP14. The expression of miRNA and mRNAs was in line with the validation results of RT-PCR and online datasets.
In this study, the screening of biomarkers in exosome of macrophage M2 may contribute to the prognosis of STAD patients.
胃腺癌（STAD）是胃癌（GC）最常见的组织学类型。巨噬细胞是肿瘤微环境的重要组成部分。我们试图寻找与巨噬细胞相关的潜在分子标志物，这可能有助于 STAD 的诊断和治疗。
首先，从巨噬细胞中提取外泌体进行 RNA 测序，以鉴定差异表达的 microRNAs（miRNAs）（DEmiRNAs）。然后，在癌症基因组图谱（TCGA）数据库中筛选 DEmiRNAs 和差异表达的 mRNAs（DEmRNAs）。通过 intersect 测序数据和 TCGA 数据获得与巨噬细胞 M2 极化相关的 miRNAs。采用 Pearson 相关系数法，筛选出与巨噬细胞 M2 显著相关的 mRNAs，构建巨噬细胞 M2-miRNA-mRNA 网络。随后，采用实时聚合酶链反应（RT-PCR）和在线数据集验证 DEmiRNAs 和 DEmRNAs 的表达。
RNA 测序共鉴定出 6 个 DEmiRNAs；TCGA 数据库共鉴定出 59 个 DEmiRNAs 和 1838 个 DEmRNAs。其中，鉴定出一个与巨噬细胞 M2 极化相关的共同 miRNA（hsa-miR-133a-3p）。DEmRNAs 和 DEmiRNAs 靶向的 mRNAs 之间获得 15 个共同 mRNAs。最终构建了一个核心巨噬细胞 M2-1 下调 miRNA-7 和上调 mRNAs 网络，包括 hsa-miR-133a-3p、SLC39A1、TTYH3、HAVCR2、TPM3、XPO1、POU2F1 和 MMP14。miRNA 和 mRNAs 的表达与 RT-PCR 和在线数据集的验证结果一致。
本研究筛选巨噬细胞 M2 外泌体中的生物标志物，可能有助于 STAD 患者的预后。
