研究概要
我们构建并验证了一种新的 CD4+ Tconv 相关 lncRNAs RS,其具有预测 HCC 患者生存和免疫治疗反应的潜在价值。
研究思路结论见上方概要
背景
肝细胞癌(HCC)是全球癌症相关死亡的第二大原因,CD4+ T淋巴细胞可抑制肝癌发生并介导肿瘤消退。然而,很少有研究关注CD4+ Tconv相关lncRNAs在HCC患者中的预后价值。
方法
我们从TCGA和GEO数据库获取数据,并在HCC中鉴定了CD4+Tconv相关lncRNAs。使用lasso回归构建风险评分,并使用两个验证队列对模型进行验证。还在不同临床亚组中评估了RS,并建立了列线图以进一步预测患者的结局。此外,我们通过TIMER数据库估计了免疫细胞浸润和癌症相关成纤维细胞(CAFs),并评估了RS在免疫检查点抑制剂反应中的作用。
结果
我们构建了一个与CD4+ Tconv相关的lncRNAs风险评分,包括六个lncRNAs(AC012073.1、AL031985.3、LINC01060、MKLN1-AS、MSC-AS1和TMCC1-AS1),并且该RS在验证队列和大多数临床亚组中具有良好的预测能力。RS和T分期被纳入列线图,具有最佳预测效果,且该模型与AJCC相比具有可比的OS预测能力。高风险组患者具有不良免疫反应表型,表现为巨噬细胞、CAFs高浸润,NK细胞低浸润。免疫治疗和化疗反应分析表明,低风险组患者对免疫检查点抑制剂有良好反应。
展开英文摘要原文
BACKGROUND
Hepatocellular carcinoma (HCC) is the second leading cause of cancer-related death worldwide, and CD4+ T lymphocytes can inhibit hepatocarcinogenesis and mediate tumor regression. However, few studies have focused on the prognostic power of CD4+ Tconv-related lncRNAs in HCC patients.
METHOD: We obtained data from TCGA and GEO databases and identified CD4+Tconv-related lncRNAs in HCC. The risk score was constructed using lasso regression and the model was validated using two validation cohorts. The RS was also assessed in different clinical subgroups, and a nomogram was established to further predict the patients' outcomes. Furthermore, we estimated the immune cell infiltration and cancer-associated fibroblasts (CAFs) through TIMER databases and assessed the role of RS in immune checkpoint inhibitors response.
RESULTS
We constructed a CD4+ Tconv-related lncRNAs risk score, including six lncRNAs (AC012073.1, AL031985.3, LINC01060, MKLN1-AS, MSC-AS1, and TMCC1-AS1), and the RS had good predictive ability in validation cohorts and most clinical subgroups. The RS and the T stage were included in the nomogram with optimum prediction and the model had comparable OS prediction power compared to the AJCC. Patients in the high-risk group had a poor immune response phenotype, with high infiltrations of macrophages, CAFs, and low infiltrations of NK cells. Immunotherapy and chemotherapy response analysis indicated that low-risk group patients had good reactions to immune checkpoint inhibitors.
CONCLUSION
We constructed and validated a novel CD4+ Tconv-related lncRNAs RS, with the potential predictive value of HCC patients' survival and immunotherapy response.
论文信息
- 作者
- Zhu L、Zhang XP、Xu S、Hu MG、Zhao ZM、Zhao GD、Xiao ZH、Liu R
- 单位
- Medical School of Chinese PLA, Beijing, China.China
- 期刊
- Frontiers in immunology2022