Table_1_m6A-related lncRNAs are potential biomarkers for the prognosis of COAD patients.docx

BackgroundColon adenocarcinoma (COAD) is the most common subtype of colon cancer. However, the 5-year survival rate of COAD patients remains unsatisfactory. N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) play essential roles in the occurrence and development of COAD. Herein, we are committed to establish and validate a prognostic m6A-related lncRNA signature.
MethodsWe obtained m6A-related lncRNAs by coexpression. The m6A-related lncRNA risk signature (m6ALncSig) was developed via univariate, LASSO, and multivariate Cox regression analyses. Kaplan-Meier (KM) survival curves, gene set enrichment analysis (GSEA), and nomogram generation were conducted to assess m6ALncSig. In addition, the potential immunotherapeutic signatures were also discussed. Real-time PCR and CCK8 analysis were performed to evaluate the expression and functions of lncRNA UBA6-AS1, which was selected.
ResultsThe risk signature comprising 14 m6A-related lncRNAs (m6ALncSig) was established, which possessed a superior predictive ability of prognosis. Meanwhile, m6ALncSig was linked to immune cell infiltration. The level of UBA6-AS1 expression was validated in 17 pairs of COAD samples. In cell function experiments, UBA6-AS1 knockdown attenuated cell proliferation capacity.
ConclusionsCollectively, m6ALncSig could serve as an independent predictive factor for COAD and accurately estimate the outcome for COAD patients. Importantly, UBA6-AS1 was first identified as an oncogene in COAD.

背景：结肠腺癌（Colon adenocarcinoma, COAD）是结直肠癌最常见的亚型。然而，结肠腺癌患者的5年生存率仍未达到令人满意的水平。N6-甲基腺苷（N6-methyladenosine, m6A）与长链非编码RNA（long noncoding RNAs, lncRNAs）在结肠腺癌的发生与发展过程中发挥着不可或缺的重要作用。本研究旨在构建并验证一个与m6A相关的lncRNA预后标记物。
方法：我们通过共表达分析筛选得到m6A相关lncRNA。借助单因素Cox回归、LASSO回归及多因素Cox回归分析，构建了m6A相关lncRNA风险标记物（m6ALncSig）。采用Kaplan-Meier（KM）生存曲线、基因集富集分析（gene set enrichment analysis, GSEA）以及列线图构建，对m6ALncSig的预后预测性能进行评估。此外，本研究还探讨了潜在的免疫治疗相关标记物。针对筛选得到的lncRNA UBA6-AS1，我们通过实时荧光定量PCR（real-time PCR）与CCK8实验，评估其表达水平与生物学功能。
结果：本研究成功构建了包含14个m6A相关lncRNA的风险标记物（m6ALncSig），该标记物具备优异的预后预测能力。同时，m6ALncSig与免疫细胞浸润水平显著相关。我们在17对结肠腺癌样本中验证了UBA6-AS1的表达水平。细胞功能实验结果显示，敲低UBA6-AS1会削弱细胞增殖能力。
结论：综上，m6ALncSig可作为结肠腺癌的独立预后预测因子，能够精准评估结肠腺癌患者的临床结局。尤为重要的是，本研究首次证实UBA6-AS1可作为结肠腺癌的癌基因。