Song Danjun, Wang Xi, Wang Yining, Liang Weiren, Luo Jun, Zheng Jiaping, Zhu Kai
Department of Interventional Therapy, The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital), Institute of Basic Medicine and Cancer (IBMC), Chinese Academy of Sciences, Hangzhou 310022, China.
Department of Ultrasound, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
Cancers (Basel). 2023 Mar 16;15(6):1800. doi: 10.3390/cancers15061800.
N1-methyladenosine (m1A) and long non-coding RNAs (lncRNAs) play significant roles in tumor progression in hepatocellular carcinoma (HCC). However, their association with HCC is still unclear. In this study, lncRNAs related to m1A were extracted from the mRNA expression matrix in The Cancer Genome Atlas (TCGA) database. Five m1A-related lncRNAs (, , , , and ) were identified based on lasso Cox regression and they generated a prognostic signature of HCC. The prognostic signature was identified as an independent prognosis factor in HCC patients. Moreover, the prognostic signature achieved better performance than mutation status or tumor mutational burden (TMB) scores in the stratification of patient survival. The immune landscape indicated that most immune checkpoint genes and immune cells were distributed differently between both risk groups. A higher IC of chemotherapeutics (sorafenib, nilotinib, sunitinib, and gefitinib) was observed in the high-risk group, and a lower IC of gemcitabine in the low-risk group, suggesting the potential of the prognostic signature in chemosensitivity. In addition, fifty-five potential small molecular drugs were found based on drug sensitivity and expression. Together, five m1A-related lncRNAs generated a prognostic signature that could be a promising prognostic prediction approach and therapeutic response assessment tool for HCC patients.
N1-甲基腺苷(m1A)和长链非编码RNA(lncRNA)在肝细胞癌(HCC)的肿瘤进展中发挥着重要作用。然而,它们与HCC的关联仍不明确。在本研究中,从癌症基因组图谱(TCGA)数据库的mRNA表达矩阵中提取了与m1A相关的lncRNA。基于套索Cox回归鉴定出5种与m1A相关的lncRNA(、、、和),并生成了HCC的预后特征。该预后特征被确定为HCC患者的独立预后因素。此外,在患者生存分层方面,该预后特征的表现优于突变状态或肿瘤突变负荷(TMB)评分。免疫图谱表明,大多数免疫检查点基因和免疫细胞在两个风险组之间的分布不同。在高危组中观察到化疗药物(索拉非尼、尼洛替尼、舒尼替尼和吉非替尼)的较高IC,在低危组中观察到吉西他滨的较低IC,这表明预后特征在化疗敏感性方面具有潜力。此外,基于药物敏感性和表达发现了55种潜在的小分子药物。总之,5种与m1A相关的lncRNA生成了一种预后特征,这可能是一种有前景的HCC患者预后预测方法和治疗反应评估工具。