Tang Yijie, Wang Tianyi, Zhang Anping, Zhu Jiaqi, Zhou Tingting, Zhou You-Lang, Shi Jiahai
Nantong Key Laboratory of Translational Medicine in Cardiothoracic Diseases, and Research Institution of Translational Medicine in Cardiothoracic Diseases, Affiliated Hospital of Nantong University, Nantong, China.
Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Nantong, China.
J Thorac Dis. 2023 Mar 31;15(3):1018-1035. doi: 10.21037/jtd-22-1027. Epub 2023 Mar 27.
The process of lucubrating into lung adenocarcinoma (LUAD) is of profound clinical and practical significance in improving the prognosis of LUAD patients. Multiple biomarkers are reportedly involved in the proliferation or metastasis of adenocarcinoma. However, whether the gene influences the development of LUAD remains unknown. Therefore, we aimed to elucidate the relationship between the expression of ADCY9 and the proliferation and migration of LUAD.
The gene was filtered via a survival analysis of LUAD acquired from the Gene Expression Omnibus (GEO). Then, we conducted a validation analysis and ADCY9-microRNA, microRNA-lncRNA, and ADCY9-lncRNA targeting relationship analysis through the data obtained from The Cancer Genome Atlas (TCGA) dataset. The survival curve, correlation, and prognostic analysis were implemented through bioinformatics methods. Both protein and mRNA expression levels of LUAD cell lines and LUAD patient samples (80 pairs) were detected using western blot assays and quantitative real-time polymerase chain reaction (qRT-PCR). An immunohistochemistry assay was performed to display the correlation between the expression level of the gene and prognosis in LUAD patients (2012-2013; n=115). Overexpression of cell lines SPCA1 and A549 were used for a series of cell function assays.
Compared with the expression level in adjacent normal tissues, ADCY9 expression was downregulated in LUAD tissues. Based on the result of the survival curve analysis, high expression of ADCY9 may lead to a better prognosis and may be seen as an independent predictor for LUAD patients. High expression of ADCY9-related microRNA hsa-miR-7-5p may lead to a worse prognosis, and high expression of hsa-miR-7-5p-related lncRNAs may lead to the opposite effects. Overexpression of ADCY9 restrained the proliferation, invasion, and migration abilities of SPCA1, A549 cells.
Results indicate that the gene acts as a tumor suppressor to restrain the proliferation, migration, and invasion in LUAD and can lead to a better survival or prognosis in LUAD patients.
深入研究肺腺癌(LUAD)的过程对改善LUAD患者的预后具有深远的临床和实际意义。据报道,多种生物标志物参与腺癌的增殖或转移。然而,该基因是否影响LUAD的发展仍不清楚。因此,我们旨在阐明ADCY9表达与LUAD增殖和迁移之间的关系。
通过对从基因表达综合数据库(GEO)获得的LUAD进行生存分析来筛选该基因。然后,我们利用从癌症基因组图谱(TCGA)数据集获得的数据进行验证分析以及ADCY9-微小RNA、微小RNA-长链非编码RNA和ADCY9-长链非编码RNA靶向关系分析。通过生物信息学方法进行生存曲线、相关性和预后分析。使用蛋白质印迹分析和定量实时聚合酶链反应(qRT-PCR)检测LUAD细胞系和LUAD患者样本(80对)的蛋白质和mRNA表达水平。进行免疫组织化学分析以显示该基因表达水平与LUAD患者(2012 - 2013年;n = 115)预后之间的相关性。使用细胞系SPCA1和A549的过表达进行一系列细胞功能测定。
与相邻正常组织中的表达水平相比,LUAD组织中ADCY9表达下调。基于生存曲线分析结果,ADCY9的高表达可能导致更好的预后,并且可被视为LUAD患者的独立预测指标。ADCY9相关的微小RNA hsa-miR-7-5p的高表达可能导致更差的预后,而hsa-miR-7-5p相关长链非编码RNA的高表达可能导致相反的效果。ADCY9的过表达抑制了SPCA1、A549细胞的增殖、侵袭和迁移能力。
结果表明该基因作为肿瘤抑制因子抑制LUAD的增殖、迁移和侵袭,并可导致LUAD患者更好的生存或预后。