Scientific Research Center, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Clinical Laboratory, Beidahuang Industry Group General Hospital, Harbin, China.
Medicine (Baltimore). 2024 Jul 5;103(27):e38713. doi: 10.1097/MD.0000000000038713.
In the tumor microenvironment (TME), CD8+ T cells showed stage exhaustion due to the continuous stimulation of tumor antigens. To evaluate the status of CD8+ T cells and reverse the exhaustion is the key to evaluate the prognosis and therapeutic effect of tumor patients. The aim of this study was to establish a prognostic signature that could effectively predict prognosis and response to immunotherapy in patients with hepatocellular carcinoma (HCC). We used univariate Cox analysis to obtain transcription factors associated with CD8+ T cell exhaustion from The Cancer Genome Atlas dataset. Then, the prognostic signature for transcription factors basic leucine zipper ATF-like transcription factor, Eomesodermin, and T-box protein 21 regulating T cell exhaustion was constructed using LASSO Cox regression. The relative expression levels of the mRNA of the 3 transcription factors were detected by reverse transcription-quantitative polymerase chain reaction in 23 pairs of HCC and paracancer tissues, and verified internally in The Cancer Genome Atlas dataset and externally in the International Cancer Genome Consortium dataset. Cox regression analysis showed that risk score was an independent prognostic variable. The overall survival of the high-risk group was significantly lower than that of the low-risk group. The low-risk group had higher immune scores, matrix scores, and ESTIMATE scores, and significantly increased expression levels of most immune checkpoint genes in the low-risk group. Therefore, patients with lower risk scores benefit more from immunotherapy. The combination of the 3 transcription factors can evaluate the exhaustion state of CD8+ T cells in the TME, laying a foundation for evaluating the TME and immunotherapy efficacy in patients with HCC.
在肿瘤微环境 (TME) 中，由于肿瘤抗原的持续刺激，CD8+ T 细胞表现出阶段衰竭。评估 CD8+ T 细胞的状态并逆转衰竭是评估肿瘤患者预后和治疗效果的关键。本研究旨在建立一个能够有效预测肝细胞癌 (HCC) 患者预后和对免疫治疗反应的预后签名。我们使用单变量 Cox 分析从癌症基因组图谱数据集获得与 CD8+ T 细胞衰竭相关的转录因子。然后，使用 LASSO Cox 回归构建了转录因子碱性亮氨酸拉链 ATF 样转录因子、Eomesodermin 和 T 框蛋白 21 调节 T 细胞衰竭的预后签名。通过逆转录定量聚合酶链反应检测 23 对 HCC 和癌旁组织中 3 个转录因子的 mRNA 的相对表达水平，并在癌症基因组图谱数据集和国际癌症基因组联盟数据集内部进行验证。Cox 回归分析表明，风险评分是一个独立的预后变量。高风险组的总生存率明显低于低风险组。低风险组的免疫评分、基质评分和 ESTIMATE 评分更高，低风险组的大多数免疫检查点基因的表达水平显著增加。因此，风险评分较低的患者从免疫治疗中获益更多。这 3 个转录因子的组合可以评估 TME 中 CD8+ T 细胞的衰竭状态，为评估 HCC 患者的 TME 和免疫治疗效果奠定基础。
