Prognostic stratification based on m(5)C regulators acts as a novel biomarker for immunotherapy in hepatocellular carcinoma.
Prognostic stratification based on m(5)C regulators acts as a novel biomarker for immunotherapy in hepatocellular carcinoma.
复制标题
基于 m5C 调节因子的预后分层可作为肝细胞癌免疫治疗的新型生物标志物
DOI：
10.3389/fimmu.2022.951529
复制
发表时间：
2022
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
免疫治疗是肝细胞癌（HCC）中一种有前途的抗癌策略。然而，只有有限的患者可以从中受益，目前还没有可靠的生物标志物来寻找潜在的受益者。甲基胞嘧啶（m5 C）在HCC中至关重要，但其在预测免疫治疗临床反应中的作用尚未完全阐明。在这项研究中，我们分析了来自癌症基因组图谱（TCGA）数据库的371例HCC患者，并研究了18个m5 C调节因子的表达。我们选择了6个差异表达基因（DEG）来构建预后风险模型以及2个m5 C相关诊断模型。m5 C评分的1年、3年和5年总生存期（OS）曲线下面积（AUC）分别为0.781/0.762/0.711，表明m5 C评分系统对肝癌预后预测具有理想的区分度。生存分析显示，高风险评分的患者比低风险评分的患者预后更差（p< 0.0001）。我们在6个公共队列中获得了一致的结果，并通过定量实时PCR和免疫组织化学（IHC）检测在湘雅真实世界队列中进行了验证。高m5 C评分组被预测为处于免疫逃避状态，对免疫治疗的敏感性较低，但对化疗和潜在靶向药物和制剂的敏感性较高，如司潘曲溴铵（YM-155）、阿西替尼、长春碱和多西他赛。同时，我们还建立了两个诊断模型，以区分HCC肿瘤与正常肝组织或肝硬化。总之，我们的研究有助于早期筛查HCC患者并选择可以从免疫治疗中获益的患者。更进一步，对于不太可能的受益者，这项研究为他们提供了新的潜在靶向药物和药物选择，以改善他们的预后。
Immunotherapy is a promising anti-cancer strategy in hepatocellular carcinoma (HCC). However, a limited number of patients can benefit from it. There are currently no reliable biomarkers available to find the potential beneficiaries. Methylcytosine (m5C) is crucial in HCC, but its role in forecasting clinical responses to immunotherapy has not been fully clarified. In this study, we analyzed 371 HCC patients from The Cancer Genome Atlas (TCGA) database and investigated the expression of 18 m5C regulators. We selected 6 differentially expressed genes (DEGs) to construct a prognostic risk model as well as 2 m5C-related diagnostic models. The 1-, 3-, and 5-year area under the curve (AUC) of m5C scores for the overall survival (OS) was 0.781/0.762/0.711, indicating the m5C score system had an ideal distinction of prognostic prediction for HCC. The survival analysis showed that patients with high-risk scores present a worse prognosis than the patients with low-risk scores (p< 0.0001). We got consistent results in 6 public cohorts and validated them in Xiangya real-world cohort by quantitative real-time PCR and immunohistochemical (IHC) assays. The high-m5C score group was predicted to be in an immune evasion state and showed low sensitivity to immunotherapy, but high sensitivity to chemotherapy and potential targeted drugs and agents, such as sepantronium bromide (YM-155), axitinib, vinblastine and docetaxel. Meanwhile, we also constructed two diagnostic models to distinguish HCC tumors from normal liver tissues or liver cirrhosis. In conclusion, our study helps to early screen HCC patients and select patients who can benefit from immunotherapy. Step forwardly, for the less likely beneficiaries, this study provides them with new potential targeted drugs and agents for choice to improve their prognosis.
登录
查看更多内容
DOI：
10.1038/nrclinonc.2017.88
发表时间：
2017-11
期刊：
Nature reviews. Clinical oncology
影响因子：
--
作者：
Nishino M;Ramaiya NH;Hatabu H;Hodi FS
通讯作者：
Hodi FS
影响因子：
37.3
作者：
Nombela P;Miguel-López B;Blanco S
通讯作者：
Blanco S
影响因子：
32.4
作者：
Hegde S;Leader AM;Merad M
通讯作者：
Merad M
影响因子：
64.5
作者：
Riaz N;Havel JJ;Makarov V;Desrichard A;Urba WJ;Sims JS;Hodi FS;Martín-Algarra S;Mandal R;Sharfman WH;Bhatia S;Hwu WJ;Gajewski TF;Slingluff CL Jr;Chowell D;Kendall SM;Chang H;Shah R;Kuo F;Morris LGT;Sidhom JW;Schneck JP;Horak CE;Weinhold N;Chan TA
通讯作者：
Chan TA
影响因子：
82.9
作者：
Auslander N;Zhang G;Lee JS;Frederick DT;Miao B;Moll T;Tian T;Wei Z;Madan S;Sullivan RJ;Boland G;Flaherty K;Herlyn M;Ruppin E
通讯作者：
Ruppin E