Xu Jingxuan, Song Jingjing, Chen Xinxin, Huang Yingpeng, You Tao, Zhu Ce, Shen Xian, Zhao Yaping
The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China.
The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, China.
Comput Biol Med. 2023 Mar;155:106598. doi: 10.1016/j.compbiomed.2023.106598. Epub 2023 Jan 24.
Gastric cancer (GC) ranks fifth among all malignant tumors globally, especially in East Asia, and has attracted extensive attention and research. MicroRNA (miRNA) modulation during genomic instability (GI) may be associated with the development and metastasis of malignant tumors. We aimed to identify GI-related miRNA signatures for the prediction of GC prognosis. We constructed a GI-related miRNA signature (GIMiSig) scheme based on The Cancer Genome Atlas (TCGA) training set (n = 389), which was later verified based on the TCGA test set (n = 194). GI-related miRNAs were identified by analyzing somatic mutation profiles and miRNA expression. A GI-related miRNA-gene co-expression network was also constructed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were analyzed to reveal possible biological pathways associated with GI-related miRNAs. The correlation of the GIMiSig with clinical factors of the TCGA dataset was analyzed. MiRNA mimics and inhibitors were used to evaluate the biological functions of miR-100-5p and miR-145-3p in GC cell lines AGS and MKN-45. This study identified a GI-related 12-miRNA signature for the prediction of GC prognosis. GIMiSig scores, similar to tumor stages, showed significant correlations with overall survival (OS, p < 0.05). GIMiSig showed high accuracy in predicting GC prognosis. MiR-100-5p and miR-145-3p promoted cell growth, invasion, and migration but inhibited apoptosis in GC cells. We report a reliable GI-related 12-miRNA signature for predicting GC prognosis. Furthermore, miR-100-5p and miR-145-3p may promote GC cell growth, invasion, and migration.
胃癌（GC）在全球所有恶性肿瘤中排名第五，在东亚地区尤为突出，已引起广泛关注和研究。基因组不稳定（GI）过程中的微小RNA（miRNA）调控可能与恶性肿瘤的发生和转移有关。我们旨在识别与GI相关的miRNA特征以预测GC预后。我们基于癌症基因组图谱（TCGA）训练集（n = 389）构建了一个与GI相关的miRNA特征（GIMiSig）方案，随后基于TCGA测试集（n = 194）进行了验证。通过分析体细胞突变谱和miRNA表达来鉴定与GI相关的miRNA。还构建了一个与GI相关的miRNA-基因共表达网络。对基因本体论（GO）和京都基因与基因组百科全书（KEGG）进行分析，以揭示与GI相关的miRNA可能相关的生物学途径。分析了GIMiSig与TCGA数据集临床因素的相关性。使用miRNA模拟物和抑制剂评估miR-100-5p和miR-145-3p在GC细胞系AGS和MKN-45中的生物学功能。本研究确定了一个用于预测GC预后的与GI相关的12-miRNA特征。GIMiSig评分与肿瘤分期相似，与总生存期（OS，p < 0.05）显示出显著相关性。GIMiSig在预测GC预后方面具有较高的准确性。miR-100-5p和miR-145-3p促进GC细胞的生长、侵袭和迁移，但抑制其凋亡。我们报告了一个用于预测GC预后的可靠的与GI相关的12-miRNA特征。此外，miR-100-5p和miR-145-3p可能促进GC细胞的生长、侵袭和迁移。
