Li Dan, Liu Xiaoli, Jiang Ni, Ke Di, Guo Qiang, Zhai Kui, Han Hao, Xiao Xue, Fan Tengyang
Department of General Medicine, Affiliated Hospital of Zunyi Medical University Zunyi 563003, Guizhou, China.
Department of Oncology, Huanggang Central Hospital Huanggang 438000, Hubei, China.
Am J Cancer Res. 2022 Jul 15;12(7):2966-2988. eCollection 2022.
Long non-coding RNA ITGB1-DT is involved in the regulation of cancer growth and metastasis. However, the roles of ITGB1-DT in non-small cell lung cancer (NSCLC) progression and sensitivity to cisplatin has not been elucidated. ITGB1-DT expression in NSCLC tissues, and the relationship between ITGB1-DT expression with NSCLC diagnosis, prognosis, clinicopathological features, and immune cell infiltration were investigated in The Cancer Gene Atlas (TCGA) database. The roles and mechanisms of ITGB1-DT in cell growth, migration, and drug sensitivity of NSCLC cells were explored in the cell model. The prognostic nomograms of ITGB1-DT-related genes were evaluated using bioinformatics. ITGB1-DT was overexpressed in NSCLC. Elevated ITGB1-DT expression was related to the late T stage, N stage, M stage, short overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) of NSCLC patients. ITGB1-DT was the independent risk factors for poor prognosis, and had diagnostic value for NSCLC patients. Interfering with the ITGB1-DT expression can inhibit the proliferation, migration, and invasion of A549, H1299, and drug-resistant A549/DDP, possibly due to the inhibition of p38 MAPK and ERK phosphorylation levels. ITGB1-DT expression was correlated with the levels of NSCLC immune infiltration cells, such as the TReg, Th, and NK cells. ITGB1-DT-related gene nomograms were associated with the prognosis, and were expected to evaluate the prognosis of NSCLC patients. In conclusion, inhibition of ITGB1-DT expression delayed the growth and metastasis of NSCLC using the MAPK/ERK signaling mechanism and enhanced the sensitivity of NSCLC to cisplatin drugs. These results indicate that ITGB1-DT might be a biomarker for evaluating the diagnosis and prognosis of NSCLC patients.
长链非编码RNA ITGB1-DT参与癌症生长和转移的调控。然而,ITGB1-DT在非小细胞肺癌(NSCLC)进展和顺铂敏感性中的作用尚未阐明。在癌症基因图谱(TCGA)数据库中研究了NSCLC组织中ITGB1-DT的表达,以及ITGB1-DT表达与NSCLC诊断、预后、临床病理特征和免疫细胞浸润之间的关系。在细胞模型中探讨了ITGB1-DT在NSCLC细胞生长、迁移和药物敏感性中的作用及机制。使用生物信息学评估了ITGB1-DT相关基因的预后列线图。ITGB1-DT在NSCLC中高表达。ITGB1-DT表达升高与NSCLC患者的晚期T分期、N分期、M分期、较短的总生存期(OS)、疾病特异性生存期(DSS)和无进展生存期(PFI)相关。ITGB1-DT是预后不良的独立危险因素,对NSCLC患者具有诊断价值。干扰ITGB1-DT表达可抑制A549、H1299和耐药A549/DDP细胞的增殖、迁移和侵袭,可能是由于抑制了p38 MAPK和ERK磷酸化水平。ITGB1-DT表达与NSCLC免疫浸润细胞如调节性T细胞(TReg)、辅助性T细胞(Th)和自然杀伤细胞(NK)的水平相关。ITGB1-DT相关基因列线图与预后相关,有望用于评估NSCLC患者的预后。总之,抑制ITGB1-DT表达通过MAPK/ERK信号机制延缓了NSCLC的生长和转移,并增强了NSCLC对顺铂药物的敏感性。这些结果表明,ITGB1-DT可能是评估NSCLC患者诊断和预后的生物标志物。