整合素β1反义转录本/芳香烃受体核转运蛋白2轴可能是肺腺癌中的一种新型生物标志物：生物信息学分析与实验验证
ITGB1-DT/ARNTL2 axis may be a novel biomarker in lung adenocarcinoma: a bioinformatics analysis and experimental validation.
作者信息
Qiu Bai-Quan, Lin Xia-Hui, Lai Song-Qing, Lu Feng, Lin Kun, Long Xiang, Zhu Shu-Qiang, Zou Hua-Xi, Xu Jian-Jun, Liu Ji-Chun, Wu Yong-Bing
机构信息
Department of Cardiothoracic Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China.
Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Shanghai, China.
出版信息
Cancer Cell Int. 2021 Dec 14;21(1):665. doi: 10.1186/s12935-021-02380-2.
BACKGROUND
Lung cancer is one of the most lethal malignant tumors that endangers human health. Lung adenocarcinoma (LUAD) has increased dramatically in recent decades, accounting for nearly 40% of all lung cancer cases. Increasing evidence points to the importance of the competitive endogenous RNA (ceRNA) intrinsic mechanism in various human cancers. However, behavioral characteristics of the ceRNA network in lung adenocarcinoma need further study.
METHODS
Groups based on SLC2A1 expression were used in this study to identify associated ceRNA networks and potential prognostic markers in lung adenocarcinoma. The Cancer Genome Atlas (TCGA) database was used to obtain the patients' lncRNA, miRNA, and mRNA expression profiles, as well as clinical data. Informatics techniques were used to investigate the effect of hub genes on prognosis. The Cox regression analyses were performed to evaluate the prognostic effect of hub genes. The methylation, GSEA, and immune infiltration analyses were utilized to explore the potential mechanisms of the hub gene. The CCK-8, transwell, and colony formation assays were performed to detect the proliferation and invasion of lung cancer cells.
RESULTS
We eventually identified the ITGB1-DT/ARNTL2 axis as an independent fact may promote lung adenocarcinoma progression. Furthermore, methylation analysis revealed that hypo-methylation may cause the dysregulated ITGB1-DT/ARNTL2 axis, and immune infiltration analysis revealed that the ITGB1-DT/ARNTL2 axis may affect the immune microenvironment and the progression of lung adenocarcinoma. The CCK-8, transwell, and colonu formation assays suggested that ITGB1-DT/ARNTL2 promotes the progression of lung adenocarcinoma. And hsa-miR-30b-3p reversed the ITGB1/ARNTL2-mediated oncogenic processes.
CONCLUSION
Our study identified the ITGB1-DT/ARNTL2 axis as a novel prognostic biomarker affects the prognosis of lung adenocarcinoma.
背景
肺癌是危害人类健康的最致命恶性肿瘤之一。近几十年来，肺腺癌（LUAD）的发病率急剧上升，占所有肺癌病例的近40%。越来越多的证据表明竞争性内源性RNA（ceRNA）内在机制在各种人类癌症中具有重要性。然而，肺腺癌中ceRNA网络的行为特征需要进一步研究。
方法
本研究基于SLC2A1表达分组，以鉴定肺腺癌中相关的ceRNA网络和潜在的预后标志物。利用癌症基因组图谱（TCGA）数据库获取患者的lncRNA、miRNA和mRNA表达谱以及临床数据。采用信息学技术研究枢纽基因对预后的影响。进行Cox回归分析以评估枢纽基因的预后作用。利用甲基化、基因集富集分析（GSEA）和免疫浸润分析来探索枢纽基因的潜在机制。进行CCK-8、Transwell和集落形成实验以检测肺癌细胞的增殖和侵袭。
结果
我们最终确定ITGB1-DT/ARNTL2轴是一个可能促进肺腺癌进展的独立因素。此外，甲基化分析显示低甲基化可能导致ITGB1-DT/ARNTL2轴失调，免疫浸润分析显示ITGB1-DT/ARNTL2轴可能影响免疫微环境和肺腺癌的进展。CCK-8、Transwell和集落形成实验表明ITGB1-DT/ARNTL2促进肺腺癌的进展。并且hsa-miR-30b-3p逆转了ITGB1/ARNTL2介导的致癌过程。
结论
我们的研究确定ITGB1-DT/ARNTL2轴是一种影响肺腺癌预后的新型预后生物标志物。
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