Xiong Zhizhong, Li Xianzhe, Yin Shi, Xie Minghao, Mao Chaobin, Zhang Fengxiang, Chen Huaxian, Jin Longyang, Lian Lei
Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China.
Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, Guangdong Institute of Gastroenterology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Front Mol Biosci. 2021 Oct 12;8:724889. doi: 10.3389/fmolb.2021.724889. eCollection 2021.
Accumulating evidence indicates that N6-methyladenosine-related long non-coding RNAs (m6A-related lncRNAs) play a crucial role in the occurrence and development of several cancers. We aimed to explore the potential role of m6A-related lncRNA signatures in predicting prognosis for early-stage (stages I and II) colorectal cancer (CRC). m6A-related lncRNA data were obtained from The Cancer Genome Atlas. Univariate Cox regression analysis was used to screen for prognostic m6A-related lncRNAs. Immune characteristics were analyzed in different subgroups created via unsupervised clustering analysis. Next, patients were randomly divided into training and test cohorts. In the training cohort, least absolute shrinkage and selection operator (LASSO) regression was performed to establish a prognostic model. The predictive value of the signature was evaluated in the training and test cohorts. Drug sensitivity was also examined. A total of 1,478 m6A-related lncRNAs were identified. Two subgroups were created based on the expression of seven prognostic m6A-related lncRNAs. Prognosis was worse for cluster 1 than for cluster 2, and cluster 1 was characterized by increased numbers of M2 macrophages, decreased numbers of memory B cells, and higher expression of checkpoint genes when compared with cluster 2. Five m6A-related lncRNAs were selected to establish a risk prediction signature via LASSO regression. The 3 years overall survival (OS) was higher in the low-risk group than in the high-risk group. The area under the curve at 1, 2, and 3 years was 0.929, 0.954, and 0.841 in the training cohort and 0.664, 0.760, and 0.754 in the test cohort, respectively. Multivariate Cox regression analysis suggests that the risk score was an independent predictor of OS in both the training and test cohorts. A prognostic nomogram based on the five m6A-related lncRNAs and their clinical features was built and verified. The high-risk group was more sensitive to chemotherapeutic drugs (camptothecin and cisplatin) than the low-risk group. We identified two molecular subgroups of early-stage CRC with unique immune features based on seven prognostic m6A-related lncRNAs. Subsequent analyses demonstrated the usefulness of a five m6A-related lncRNA signature as a potential indicator of prognosis in patients with early-stage CRC.
越来越多的证据表明，N6-甲基腺嘌呤相关的长链非编码RNA（m6A相关lncRNA）在多种癌症的发生和发展中起关键作用。我们旨在探讨m6A相关lncRNA特征在预测早期（I期和II期）结直肠癌（CRC）预后中的潜在作用。m6A相关lncRNA数据来自癌症基因组图谱。采用单变量Cox回归分析筛选预后性m6A相关lncRNA。通过无监督聚类分析在不同亚组中分析免疫特征。接下来，将患者随机分为训练组和测试组。在训练组中，进行最小绝对收缩和选择算子（LASSO）回归以建立预后模型。在训练组和测试组中评估该特征的预测价值。还检查了药物敏感性。共鉴定出1478个m6A相关lncRNA。根据7个预后性m6A相关lncRNA的表达创建了两个亚组。与第2组相比，第1组的预后更差，且第1组的特征是M2巨噬细胞数量增加、记忆B细胞数量减少以及检查点基因表达更高。通过LASSO回归选择5个m6A相关lncRNA以建立风险预测特征。低风险组的3年总生存率高于高风险组。训练组中1年、2年和3年的曲线下面积分别为0.929、0.954和0.841，测试组中分别为0.664、0.760和0.754。多变量Cox回归分析表明，风险评分在训练组和测试组中均是总生存的独立预测因子。构建并验证了基于5个m6A相关lncRNA及其临床特征的预后列线图。高风险组比低风险组对化疗药物（喜树碱和顺铂）更敏感。我们基于7个预后性m6A相关lncRNA鉴定出具有独特免疫特征的早期CRC的两个分子亚组。随后的分析证明了5个m6A相关lncRNA特征作为早期CRC患者预后潜在指标的有用性。
