Novel m7G-related lncRNA signature for predicting overall survival in patients with gastric cancer.

Novel m7G-related lncRNA signature for predicting overall survival in patients with gastric cancer.
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DOI:
10.1186/s12859-023-05228-w
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发表时间:
2023-03-19
期刊:
影响因子:
3
通讯作者:
--
中科院分区:
生物学4区
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胃癌(GC)预后不良,仍然是全球疾病和死亡的主要原因之一。长非编码 RNA (lncRNA) 调节肿瘤形成,长期以来一直用于预测肿瘤预后。 N7-甲基鸟苷 (m7G) 是最常见的 RNA 修饰。 m7G-lncRNA 调节 GC 的发生和进展,但其在 GC 中的确切机制尚不清楚。本研究的目的是开发一种新的 m7G 相关 lncRNA 特征作为预测 GC 存活率和指导治疗的生物标志物。癌症基因组图谱数据库帮助提取 GC 的基因表达数据和临床信息。 Pearson 相关分析有助于指出 m7G 相关的 lncRNA。单变量 Cox 分析有助于识别具有预测能力的 m7G 相关 lncRNA。 Lasso-Cox 方法帮助指出了 7 个 lncRNA,用于建立 m7G 相关 lncRNA 预后特征 (m7G-LPS),然后构建列线图。采用Kaplan-Meier分析、单变量和多变量Cox回归分析、列线图模型校准图、受试者工作特征曲线和主成分分析来验证风险模型的可靠性。此外,q-PCR 有助于在体外验证 m7G-LPS 的 lncRNA 表达。根据风险评分的中值将研究对象分为高风险组和低风险组。基因富集分析证实了构建的m7G-LPS与RNA转录和翻译以及多种免疫相关通路的相关性。临床病理学特征的分析揭示了高危组中更多的进展特征。 CIBERSORT 分析显示 m7G-LPS 参与免疫细胞浸润。风险评分与免疫检查点基因表达、免疫细胞和免疫功能评分、免疫细胞浸润和化疗药物敏感性相关。因此,我们的研究表明,使用7种m7G相关lncRNA构建的m7G-LPS可以预测GC患者的生存时间,并作为生物标志物指导化疗和免疫治疗方案。
Presenting with a poor prognosis, gastric cancer (GC) remains one of the leading causes of disease and death worldwide. Long non-coding RNAs (lncRNAs) regulate tumor formation and have been long used to predict tumor prognosis. N7-methylguanosine (m7G) is the most prevalent RNA modification. m7G-lncRNAs regulate GC onset and progression, but their precise mechanism in GC is unclear. The objective of this research was the development of a new m7G-related lncRNA signature as a biomarker for predicting GC survival rate and guiding treatment. The Cancer Genome Atlas database helped extract gene expression data and clinical information for GC. Pearson correlation analysis helped point out m7G-related lncRNAs. Univariate Cox analysis helped in identifying m7G-related lncRNA with predictive capability. The Lasso-Cox method helped point out seven lncRNAs for the purpose of establishing an m7G-related lncRNA prognostic signature (m7G-LPS), followed by the construction of a nomogram. Kaplan–Meier analysis, univariate and multivariate Cox regression analysis, calibration plot of the nomogram model, receiver operating characteristic curve and principal component analysis were utilized for the verification of the risk model’s reliability. Furthermore, q-PCR helped verify the lncRNAs expression of m7G-LPS in-vitro. The study subjects were classified into high and low-risk groups based on the median value of the risk score. Gene enrichment analysis confirmed the constructed m7G-LPS’ correlation with RNA transcription and translation and multiple immune-related pathways. Analysis of the clinicopathological features revealed more progressive features in the high-risk group. CIBERSORT analysis showed the involvement of m7G-LPS in immune cell infiltration. The risk score was correlated with immune checkpoint gene expression, immune cell and immune function score, immune cell infiltration, and chemotherapy drug sensitivity. Therefore, our study shows that m7G-LPS constructed using seven m7G-related lncRNAs can predict the survival time of GC patients and guide chemotherapy and immunotherapy regimens as biomarker.
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