Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College Fudan University, Shanghai, China.
Cancer Med. 2023 Jan;12(1):930-948. doi: 10.1002/cam4.4851. Epub 2022 May 26.
Aerobic glycolysis is a common metabolic phenotype in tumors that helps cancer cells adjust to severe living conditions and can aid metastasis in several types of carcinomas, including colorectal cancer (CRC). Long non-coding RNAs (lncRNAs) can influence tumor biology and have been previously used to assess patients' outcomes and to identify potential therapeutic targets. However, despite the importance of glycolysis-related lncRNAs (GRLs) in the development of CRC, studies on their use as prognostic markers are still limited. Herein, we applied a series of bioinformatic analyses to screen potential prognostic lncRNAs for colorectal cancer. Out of all lncRNAs screened, nine GRLs were selected to constitute a prognostic signature. Based on the signature, two molecular subtypes were classified with distinct prognostic outcomes and excellent diagnostic accuracy (The 1-, 3- and 5-year AUC are 0.756, 0.716, and 0.721, respectively). The prognostic value of this signature was further validated using another cohort. The enriched molecular pathways, immune infiltration, and mutation landscape were also significantly different between the two groups. The different drug sensitivity results between the two groups suggest a potential strategy for precise treatment. Furthermore, we confirmed that AFAP1-AS1 could regulate aerobic glycolysis and metastasis of CRC cells. Overall, we developed a glycolysis-related lncRNA (GRL) signature and suggested that this signature could offer a predictive value and identify potential therapeutic targets for cancer therapy.
有氧糖酵解是肿瘤中的一种常见代谢表型,有助于癌细胞适应恶劣的生存条件,并能促进几种类型的癌转移,包括结直肠癌(CRC)。长链非编码 RNA(lncRNA)可以影响肿瘤生物学,以前曾被用于评估患者的预后并确定潜在的治疗靶点。然而,尽管与糖酵解相关的 lncRNA(GRL)在 CRC 的发展中很重要,但关于它们作为预后标志物的研究仍然有限。在此,我们应用了一系列生物信息学分析来筛选结直肠癌潜在的预后 lncRNA。在筛选出的所有 lncRNA 中,选择了 9 个 GRL 来构建预后特征。基于该特征,将两个分子亚型进行分类,具有不同的预后结果和出色的诊断准确性(1、3 和 5 年 AUC 分别为 0.756、0.716 和 0.721)。该特征的预后价值还使用另一个队列进行了验证。两组之间的富集分子途径、免疫浸润和突变景观也有显著差异。两组之间不同的药物敏感性结果表明了精准治疗的潜在策略。此外,我们证实了 AFAP1-AS1 可以调节 CRC 细胞的有氧糖酵解和转移。总的来说,我们开发了一个与糖酵解相关的 lncRNA(GRL)特征,并表明该特征可以提供预测价值,并为癌症治疗确定潜在的治疗靶点。