转移相关的长非编码RNA AL359220.1、SH3BP5-AS1和ZF-AS1对于肺腺癌的预后评估具有重要意义。
Metastasis-related long non-coding RNAs AL359220.1, SH3BP5-AS1 and ZF-AS1 are significant for prognostic assessment of lung adenocarcinoma.
发表日期:2023 Aug 10
作者:
Jianjun Tan, Weilin Mao, Shuzi Long, Tao Zhang
来源:
Cellular & Molecular Immunology
摘要:
肺腺癌(LUAD)的转移严重恶化了预后。肿瘤微环境(TME)中的遗传改变与LUAD的转移以及其他恶性生物学特性密切相关。在本研究中,我们建立了一个与转移相关的风险模型,以准确预测LUAD的预后。我们收集了TCGA数据库中503例肺腺癌患者的RNA测序数据及临床资料,包括肿瘤组织和54例邻近正常组织。此外,我们还在一个单一中心获取了来自156例肺腺癌患者的成对标本。通过一系列体外实验(包括Western blotting、qPCR和Transwell assay)验证了转移相关的长非编码RNA(MRLNRs)的转移相关性和临床意义。共有六个MRLNRs与LUAD患者的预后显著相关,其中AL359220.1、SH3BP5-AS1和ZF-AS1进一步建立了一个与转移相关的风险评分模型(MRRS),因为它们与LUAD患者的总生存率密切相关。根据MRRS评分,高风险组评分较高的患者获得了较差的预后和生存结果。ZFAS1在肿瘤组织中表达高,并与SH3BP5-AS1和AL359220.1相比呈相反的结果。此外,ZFAS1的高表达与更晚期的T分期和远处转移显著相关。通过siRNA降低ZFAS1的表达显著减弱了LUAD细胞的迁移和侵袭能力。在本研究中,我们阐明了AL359220.1、SH3BP5-AS1和ZF-AS1在LUAD中的转移相关性和临床意义。此外,MRRS为临床决策和LUAD的预后提供了一个有前景的评估模型。
Metastasis of lung adenocarcinoma (LUAD) severely worsens prognosis. Genetic alteration in the tumor microenvironment (TME) is closely associated with metastasis and other malignant biological properties of LUAD. In this study, we establish a metastasis-related risk model to accurately predict LUAD prognosis.RNA-sequencing profiles and clinical data of LUAD patients including 503 tumor tissues and 54 adjacent normal tissues were collected in TCGA database. Additionally, the paired specimens from 156 LUAD patients were obtained in a single center. The metastatic relevance and clinical significance of metastasis-related long non-coding RNA (MRLNRs) was validated by series of in vitro experiments including western blotting, qPCR and transwell assays.Six MRLNRs were significantly correlated to prognoses of LUAD patients, of which AL359220.1, SH3BP5-AS1 and ZF-AS1 were further used to establish a metastasis-related risk scoring model (MRRS) due to the close associations with overall survival of LUAD patients. According to the MRRS, patients with higher scores in the high-risk group obtained poorer prognoses and survival outcomes. ZFAS1 expressed highly in tumor tissues and showed the inverse results compared to SH3BP5-AS1 and AL359220.1. In addition, the high expression of ZFAS1 was prominently correlated to the more advanced T-stage and distant metastasis. The reduction of ZFAS1 induced by siRNAs dramatically diminished the migration and invasion abilities of LUAD cells.In the present research, we elucidate the metastatic relevance and clinical significance of AL359220.1, SH3BP5-AS1 and ZF-AS1 in LUAD. Moreover, MRRS provide a promising assessing model for clinical decision making and prognosis of LUAD.