Department of Oncology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Department of Oncology, Three Gorges Hospital of Chongqing University, Chongqing 404000, China.
Aging (Albany NY). 2023 Aug 10;15(15):7551-7564. doi: 10.18632/aging.204923.
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 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.
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 的转移和其他恶性生物学特性密切相关。在这项研究中，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。
从 TCGA 数据库中收集了包括 503 个肿瘤组织和 54 个相邻正常组织的 LUAD 患者的 RNA-seq 图谱和临床数据。此外，在一个中心还获得了 156 名 LUAD 患者的配对标本。通过一系列实验，包括 Western blot、qPCR 和 Transwell 测定，验证了转移相关长非编码 RNA（MRLNRs）的转移相关性和临床意义。
有 6 个 MRLNRs 与 LUAD 患者的预后显著相关，其中 AL359220.1、SH3BP5-AS1 和 ZF-AS1 由于与 LUAD 患者的总生存率密切相关，因此进一步用于建立转移相关风险评分模型（MRRS）。根据 MRRS，高风险组患者的评分较高，预后和生存结果较差。ZFAS1 在肿瘤组织中表达较高，与 SH3BP5-AS1 和 AL359220.1 的表达呈负相关。此外，ZFAS1 的高表达与更晚期的 T 分期和远处转移显著相关。siRNAs 降低 ZFAS1 的表达显著降低了 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 LUAD 的临床决策和预后提供了一个有前途的评估模型。
