Lin Junhong, Wu Sikai, Zhu Kanghao, Zhang Jian, Shi Xiaoshun, Shen Jianfei, Xu Jianfeng
Taizhou University, Taizhou, China.
Department of Thoracic Surgery, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Key Laboratory of Minimally Invasive Techniques & Rapid Rehabilitation of Digestive System Tumor of Zhejiang Province, Linhai, China.
J Thorac Dis. 2022 Jul;14(7):2493-2510. doi: 10.21037/jtd-22-294.
The impact of miR-145-5p in immune infiltration and the potential application in esophageal squamous cell carcinoma (ESCC) immunochemotherapy remains unknown.
Transcriptomic data for ESCC tissues and normal tissues and clinical materials of patients with ESCC were obtained from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differences in mRNA levels in cancer tissues and noncancerous tissues were analyzed, and we subsequently investigated the association between miR-145-5p expression and the key parameters of ESCC progression and prognosis. Additionally, cytological experiments were performed to evaluate the biological functions of miR-145-5p. Pathways potentially affected by miR-145-5p were analyzed by Gene Set Enrichment Analysis (GSEA) and REACTOME. We also analyzed the function of miR-145-5p in immune infiltration through the TIMER2 (Tumor Immune Estimation Resource) database.
The analysis of gene chip data from the TCGA database and GEO database (including GSE13937 and GSE43732) showed that the expression of miR-145-5p is downregulated in ESCC (P<0.05) and that patients with high miR-145-5p levels had lower survival rates (P<0.05). The expression of miR-145-5p was significantly correlated with the disease-free survival (DFS) rate (P<0.05) and M stage (P<0.05) in the TCGA database and was significantly correlated with the T stage (P<0.05) and TNM stage (P<0.05) in the GSE13937 database. Functional experiments showed that miR-145-5p attenuated proliferation (P<0.05), migration (P<0.01) and invasion (P<0.01) in the Eca109 cell line. Both GSEA gene enrichment and REACTOME gene enrichment revealed that miR-145-5p was associated with tumor signaling pathways and immune signaling pathways. Immune infiltration analysis revealed that the expression level of miR-145-5p was significantly correlated with the infiltration level of macrophages (P<0.05) and was positively correlated with the level of gene markers of M2 macrophages and tumor-associated macrophages (P<0.05).
MiR-145-5p acts as a tumor suppressor microRNA in ESCC and is an important noncoding RNA in the high M2-like tumor-associated macrophage infiltration of ESCC. Assessing the miR-145-5p level in ESCC samples has translational meaning, which help illustrate the immune infiltration status, predict the prognostic outcome, and select the type of immunochemotherapy.
miR-145-5p在免疫浸润中的作用以及在食管鳞状细胞癌（ESCC）免疫化疗中的潜在应用尚不清楚。
从癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）获取ESCC组织和正常组织的转录组数据以及ESCC患者的临床资料。分析癌组织和非癌组织中mRNA水平的差异，随后研究miR-145-5p表达与ESCC进展和预后关键参数之间的关联。此外，进行细胞学实验以评估miR-145-5p的生物学功能。通过基因集富集分析（GSEA）和REACTOME分析可能受miR-145-5p影响的通路。我们还通过肿瘤免疫估计资源（TIMER2）数据库分析miR-145-5p在免疫浸润中的功能。
对TCGA数据库和GEO数据库（包括GSE13937和GSE43732）的基因芯片数据进行分析，结果显示ESCC中miR-145-5p表达下调（P<0.05），且miR-145-5p水平高的患者生存率较低（P<0.05）。在TCGA数据库中，miR-145-5p表达与无病生存率（DFS）（P<0.05）和M分期（P<0.05）显著相关，在GSE13937数据库中与T分期（P<0.05）和TNM分期（P<0.05）显著相关。功能实验表明，miR-145-5p可减弱Eca109细胞系的增殖（P<0.05）、迁移（P<0.01）和侵袭（P<0.01）。GSEA基因富集和REACTOME基因富集均显示miR-145-5p与肿瘤信号通路和免疫信号通路相关。免疫浸润分析显示，miR-145-5p表达水平与巨噬细胞浸润水平显著相关（P<0.05），与M2巨噬细胞和肿瘤相关巨噬细胞的基因标志物水平呈正相关（P<0.05）。
miR-145-5p在ESCC中作为肿瘤抑制性微小RNA发挥作用，是ESCC中高M2样肿瘤相关巨噬细胞浸润的重要非编码RNA。评估ESCC样本中的miR-145-5p水平具有转化意义，有助于阐明免疫浸润状态、预测预后结果并选择免疫化疗类型。
