Lin Zhichao, Huang Wenhai, Xie Zehua, Yi Yongsheng, Li Zumei
Department of Thoracic Surgery, Jiangmen Central Hospital, Affiliated Jiangmen Hospital of Sun Yat-sen University, Jiangmen, 529030, People's Republic of China.
Int J Gen Med. 2022 Aug 6;15:6451-6464. doi: 10.2147/IJGM.S375761. eCollection 2022.
Based on bioinformatics analysis and experimental validation, we investigated the expression, clinical significance, immune infiltration, and potential signaling pathways of miR-3940-5p in lung adenocarcinoma (LUAD).
521 LUAD tissue samples and 46 normal lung tissue samples from The Cancer Genome Atlas (TCGA) database. We evaluated the relationship between clinical features and miR-3940-5p expression using Kruskal-Wallis, Wilcoxon sign-rank, and logistic regression, explored the relationship between miR-3940-5p expression and the prognosis of LUAD patients using Kaplan-Meier survival curve analysis. Several databases were used to identify miRNA targets. MiR-3940-5p target genes were analyzed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. The significant role of miR-3940-5p in function was evaluated using immune infiltration analysis. LUAD cell lines were tested for miR-3940-5p expression using QRT-PCR.
There was a significant association between high miR-3940-5p expression in LUAD and T stage (P=0.005), pathologic stage (P=0.047), race (White vs Asian & Black or African American) (P=0.041), residual tumor (P=0.043), and anatomic neoplasm subdivision2 (P=0.030). MiR-3940-5p expression predicted poor overall survival (HR: 1.35; 95% CI: 1.01-1.81; P=0.045), disease-specific survival (HR: 1.53; 95% CI: 1.05-2.23; P=0.026), and progression-free survival (HR: 1.35; 95% CI: 1.03-1.77; P=0.032). BAP1, BBS1, CCR2, KCNE3, PEBP1, and RABL2A were all associated with poor OS in LUAD patients with low miR-3940-5p expression levels. According to GO and KEGG analyses, miR-3940-5p may play a role in LUAD development by regulating pathways such as measles, PI3K-Akt signaling pathway, and p53 signaling pathway. There was a correlation between the expression level of miR-3940-5p and immune infiltration. LUAD cell lines showed significantly higher levels of miR-3940-5p than Beas-2B cells.
A high expression of miR-3940-5p is significantly associated with a poor prognosis in patients with LUAD, suggesting that it could be used as a prognostic biomarker.
基于生物信息学分析和实验验证，我们研究了miR-3940-5p在肺腺癌（LUAD）中的表达、临床意义、免疫浸润及潜在信号通路。
来自癌症基因组图谱（TCGA）数据库的521例LUAD组织样本和46例正常肺组织样本。我们使用Kruskal-Wallis检验、Wilcoxon符号秩检验和逻辑回归评估临床特征与miR-3940-5p表达之间的关系，使用Kaplan-Meier生存曲线分析探索miR-3940-5p表达与LUAD患者预后之间的关系。使用多个数据库鉴定miRNA靶标。基于基因本体论（GO）和京都基因与基因组百科全书（KEGG）分析对miR-3940-5p靶基因进行分析。使用免疫浸润分析评估miR-3940-5p在功能方面的重要作用。使用QRT-PCR检测LUAD细胞系中miR-3940-5p的表达。
LUAD中miR-3940-5p高表达与T分期（P = 0.005）、病理分期（P = 0.047）、种族（白人vs亚洲人和黑人或非裔美国人）（P = 0.041）、残留肿瘤（P = 0.043）和解剖肿瘤细分2（P = 0.030）之间存在显著关联。miR-3940-5p表达预测总生存期较差（HR：1.35；95%CI：1.01 - 1.81；P = 0.045）、疾病特异性生存期较差（HR：1.53；95%CI：1.05 - 2.23；P = 0.026）和无进展生存期较差（HR：1.35；95%CI：1.03 - 1.77；P = 0.032）。在miR-3940-5p表达水平低的LUAD患者中，BAP1、BBS1、CCR2、KCNE3、PEBP1和RABL2A均与较差的总生存期相关。根据GO和KEGG分析，miR-3940-5p可能通过调节麻疹、PI3K-Akt信号通路和p53信号通路等途径在LUAD发展中发挥作用。miR-3940-5p的表达水平与免疫浸润之间存在相关性。LUAD细胞系显示出比Beas-2B细胞显著更高水平的miR-3940-5p。
miR-3940-5p高表达与LUAD患者的不良预后显著相关，表明它可作为一种预后生物标志物。
