Department of Gastroenterology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Branch Center of Advanced Medical Research Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Pathol Oncol Res. 2022 Aug 11;28:1610536. doi: 10.3389/pore.2022.1610536. eCollection 2022.
The RNA methylation of N6 adenosine (m6A) plays a crucial role in various biological processes. Strong evidence reveals that the dysregulation of long non-coding RNAs (lncRNA) brings about the abnormality of downstream signaling in multiple ways, thus influencing tumor initiation and progression. Currently, it is essential to discover effective and succinct molecular biomarkers for predicting colorectal cancer (CRC) prognosis. However, the prognostic value of m6A-related lncRNAs for CRC remains unclear, especially for progression-free survival (PFS). Here, we screened 24 m6A-related lncRNAs in 622 CRC patients and identified five lncRNAs (SLCO4A1-AS1, MELTF-AS1, SH3PXD2A-AS1, H19 and PCAT6) associated with patient PFS. Compared to normal samples, their expression was up-regulated in CRC tumors from TCGA dataset, which was validated in 55 CRC patients from our in-house cohort. We established an m6A-Lnc signature for predicting patient PFS, which was an independent prognostic factor by classification analysis of clinicopathologic features. Moreover, the signature was validated in 1,077 patients from six independent datasets (GSE17538, GSE39582, GSE33113, GSE31595, GSE29621, and GSE17536), and it showed better performance than three known lncRNA signatures for predicting PFS. In summary, our study demonstrates that the m6A-Lnc signature is a promising biomarker for forecasting patient PFS in CRC.
N6 腺苷的 RNA 甲基化（m6A）在各种生物过程中起着至关重要的作用。强有力的证据表明，长非编码 RNA（lncRNA）的失调以多种方式导致下游信号的异常，从而影响肿瘤的发生和进展。目前，发现有效的、简洁的分子生物标志物来预测结直肠癌（CRC）的预后至关重要。然而，m6A 相关 lncRNA 对 CRC 的预后价值尚不清楚，特别是对无进展生存期（PFS）。在这里，我们在 622 例 CRC 患者中筛选了 24 个 m6A 相关 lncRNA，并鉴定了 5 个与患者 PFS 相关的 lncRNA（SLCO4A1-AS1、MELTF-AS1、SH3PXD2A-AS1、H19 和 PCAT6）。与正常样本相比，它们在 TCGA 数据集的 CRC 肿瘤中的表达上调，在我们内部队列的 55 例 CRC 患者中得到了验证。我们建立了一个 m6A-Lnc 签名来预测患者 PFS，通过对临床病理特征的分类分析，它是一个独立的预后因素。此外，该签名在来自六个独立数据集（GSE17538、GSE39582、GSE33113、GSE31595、GSE29621 和 GSE17536）的 1077 例患者中得到了验证，并且它在预测 PFS 方面的表现优于三个已知的 lncRNA 签名。总之，我们的研究表明，m6A-Lnc 签名是预测 CRC 患者 PFS 的有前途的生物标志物。
