Bai Zhihui, Xia Qianlin, Xu Wanli, Wu Zhirong, He Xiaomeng, Zhang Xin, Wang Zhefeng, Luo Mengting, Sun Huaqin, Liu Songmei, Wang Jin
Central Laboratory, Zhongshan Hospital (Xiamen), Fudan University, Xiamen, 361015, China.
Xiamen Key Laboratory of Biotherapy, Xiamen, 361015, China.
Cell Mol Life Sci. 2025 Jan 21;82(1):48. doi: 10.1007/s00018-024-05573-w.
Emerging evidence has shown that the N-methyladenosine (mA) modification of RNA plays key roles in tumorigenesis and the progression of various cancers. However, the potential roles of the mA modification of long noncoding RNAs (lncRNAs) in pancreatic cancer (PaCa) are still unknown. To analyze the prognostic value of mA-related lncRNAs in PaCa, an m6A-related lncRNA signature was constructed as a risk model via Pearson's correlation and univariate Cox regression analyses in The Cancer Genome Atlas (TCGA) database. The tumor microenvironment (TME), tumor mutation burden, and drug sensitivity of PaCa were investigated by mA-related lncRNA risk score analyses. We established an mA-related risk prognostic model consisting of five lncRNAs, namely, LINC01091, AC096733.2, AC092171.5, AC015660.1, and AC005332.6, which not only revealed significant differences in immune cell infiltration associated with the TME between the high-risk and low-risk groups but also predicted the potential benefit of immunotherapy for patients with PaCa. Drugs such as WZ8040, selumetinib, and bortezomib were also identified as more effective for high-risk patients. Our results indicate that the mA-related lncRNA risk model could be an independent prognostic indicator, which may provide valuable insights for identifying therapeutic approaches for PaCa.
越来越多的证据表明,RNA的N-甲基腺苷(m⁶A)修饰在肿瘤发生及各种癌症进展中起关键作用。然而,长链非编码RNA(lncRNA)的m⁶A修饰在胰腺癌(PaCa)中的潜在作用仍不清楚。为分析m⁶A相关lncRNA在PaCa中的预后价值,通过Pearson相关性分析和单变量Cox回归分析,在癌症基因组图谱(TCGA)数据库中构建了一个与m⁶A相关的lncRNA特征作为风险模型。通过与m⁶A相关的lncRNA风险评分分析,研究了PaCa的肿瘤微环境(TME)、肿瘤突变负荷和药物敏感性。我们建立了一个由五个lncRNA组成的与m⁶A相关的风险预后模型,即LINC01091、AC096733.2、AC092171.5、AC015660.1和AC005332.6,该模型不仅揭示了高风险组和低风险组之间与TME相关的免疫细胞浸润存在显著差异,还预测了免疫疗法对PaCa患者的潜在益处。还确定WZ8040、司美替尼和硼替佐米等药物对高风险患者更有效。我们的结果表明,与m⁶A相关的lncRNA风险模型可能是一个独立的预后指标,这可能为确定PaCa的治疗方法提供有价值的见解。