Cheng Zhichao, Wang Jiaqi, Xu Yixin, Jiang Tao, Xue Zhenyu, Li Shuai, Zhao Ying, Song Hu, Song Jun
The Graduate School, Xuzhou Medical University, Xuzhou, Jiangsu, China.
Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China.
Front Oncol. 2022 Sep 15;12:951452. doi: 10.3389/fonc.2022.951452. eCollection 2022.
Colon adenocarcinoma (COAD) is a prevalent malignant tumor that severely threatens human health across the globe. Immunotherapy is an essential need for patients with COAD. N7-methylguanosine (m7G) has been associated with human diseases, and non-coding RNAs (lncRNAs) regulate various tumor-related biological processes. Nonetheless, the m7G-related lncRNAs involved in COAD regulation are limited. This study aims to construct the clustering features and prognostic model of m7G-related lncRNAs in COAD. First, The Cancer Genome Atlas (TCGA) database was used to identify m7G-related differentially expressed lncRNAs (DELs), based on which COAD cases could be classified into two subtypes. Subsequently, univariate Cox analysis was used to identify 9 prognostic m7G-related lncRNAs. Further, Five candidates were screened by LASSO-Cox regression to develop new models. The patients were divided into high-risk and low-risk groups based on the median risk score. Consequently, the Kaplan-Meier survival curve demonstrated a statistically significant overall survival (OS) between the high- and low-risk groups (P<0.001). Multivariate Cox regression analysis revealed that risk score is an independent prognostic factor in COAD patients (P<0.001). This confirms the clinical applicability of the model. Additionally, we performed Gene Set Enrichment Analysis (GSEA), which uncovered the biological and functional differences between risk subgroups, i.e., enrichment of immune-related diseases in the high-risk group and enrichment of metabolic-related pathways in the low-risk group. In a drug sensitivity analysis, high-risk group were more sensitive to some chemotherapeutics and targeted drugs than low-risk group. Eventually, the stability of the model was confirmed by qRT-PCR. Our study unraveled the features of different immune states of COAD and established a prognostic model, including five m7G-related lncRNAs for COAD patients. These results will bolster clinical treatment and survival prediction of COAD.
结肠腺癌(COAD)是一种普遍存在的恶性肿瘤,严重威胁着全球人类健康。免疫疗法是COAD患者的迫切需求。N7-甲基鸟苷(m7G)与人类疾病有关,非编码RNA(lncRNAs)调节各种肿瘤相关的生物学过程。然而,参与COAD调节的m7G相关lncRNAs有限。本研究旨在构建COAD中m7G相关lncRNAs的聚类特征和预后模型。首先,利用癌症基因组图谱(TCGA)数据库鉴定m7G相关的差异表达lncRNAs(DELs),据此可将COAD病例分为两种亚型。随后,采用单因素Cox分析鉴定出9个与预后相关的m7G相关lncRNAs。进一步地,通过LASSO-Cox回归筛选出5个候选基因以建立新模型。根据中位风险评分将患者分为高风险组和低风险组。因此,Kaplan-Meier生存曲线显示高风险组和低风险组之间的总生存期(OS)具有统计学显著差异(P<0.001)。多因素Cox回归分析显示风险评分是COAD患者的独立预后因素(P<0.001)。这证实了该模型的临床适用性。此外,我们进行了基因集富集分析(GSEA),发现了风险亚组之间的生物学和功能差异,即高风险组中免疫相关疾病富集,低风险组中代谢相关途径富集。在药物敏感性分析中,高风险组比低风险组对某些化疗药物和靶向药物更敏感。最终,通过qRT-PCR证实了模型的稳定性。我们的研究揭示了COAD不同免疫状态的特征,并建立了一个预后模型,其中包括5个与COAD患者相关的m7G相关lncRNAs。这些结果将有助于COAD的临床治疗和生存预测。