Nankai University School of Medicine, Nankai University, Tianjin, China.
Faculty of Hepato-Pancreato-Biliary Surgery, Chinese PLA General Hospital, Beijing, China.
Front Immunol. 2023 Feb 6;14:1114717. doi: 10.3389/fimmu.2023.1114717. eCollection 2023.
Immunotherapy has been the first-line treatment option in advanced Hepatocellular Carcinoma(HCC); but now, there are no established molecular markers that can predict immunotherapy response. Estrogen has a crucial role in the development of a variety of liver illnesses, including liver fibrosis, Nonalcoholic fatty liver disease (NAFLD), and HCC. Nonetheless, the significance of estrogen-related genes in HCC immunotherapy and the underlying molecular mechanisms are not yet fully understood.
In this study, we constructed a novel estrogen-related gene prognostic signature (ERGPS) by analyzing bulk RNA sequencing data from 365 HCC patients. Based on the median risk score, we divided 365 HCC patients into low- and high-risk groups. Tumor mutation burden (TMB), Microsatellite instability (MSI), T cell receptor (TCR) richness, B cell receptor (BCR) richness, single-nucleotide variants (SNV) Neoantigens, Cancer Testicular Antigens (CTA) scores, and Tumour Immune Dysfunction and Exclusion (TIDE) scores were used to evaluate the magnitude of immunotherapy response. Multiple external datasets validate the validity and robustness of the prognostic signature. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to validate estrogen-related gene overexpression in HCC tissue samples.
ERGPS is an independent risk factor affecting the prognosis of HCC patients and is superior to other clinical variables in predicting patient survival and immunotherapy response. Multiple independent external datasets confirmed the superior predictive efficacy of the prognostic signature. The prognostic signature was positively correlated with TMB score, MSI score, TCR richness, BCR richness, SNV Neoantigens score, CTA score, expression levels of immune checkpoint-related genes, and TIDE score. Patients with HCC in the high-risk group identified by the prognostic signature were likely to be more responsive to immunotherapy and more suitable for immunotherapy. qRT-PCR confirmed that estrogen-related genes of the construct signature were highly expressed in HCC tumor tissues.
Estrogen-related genes are overexpressed in HCC tissues. Our novel prognostic signature can accurately predict not only the prognosis but also the immunotherapy response of HCC patients. In the future, prognostic signatures will be a useful tool for clinicians to screen patients with HCC who are suitable for immunotherapy.
免疫疗法已成为晚期肝细胞癌（HCC）的一线治疗选择；但目前，尚无确定的分子标志物可以预测免疫治疗反应。雌激素在多种肝脏疾病的发展中起着关键作用，包括肝纤维化、非酒精性脂肪性肝病（NAFLD）和 HCC。然而，雌激素相关基因在 HCC 免疫治疗中的意义及其潜在的分子机制尚不完全清楚。
在这项研究中，我们通过分析 365 名 HCC 患者的批量 RNA 测序数据构建了一个新的雌激素相关基因预后特征（ERGPS）。根据中位数风险评分，我们将 365 名 HCC 患者分为低风险组和高风险组。肿瘤突变负担（TMB）、微卫星不稳定性（MSI）、T 细胞受体（TCR）丰富度、B 细胞受体（BCR）丰富度、单核苷酸变异（SNV）新抗原、癌症睾丸抗原（CTA）评分和肿瘤免疫功能障碍和排除（TIDE）评分用于评估免疫治疗反应的幅度。多个外部数据集验证了预后特征的有效性和稳健性。实时定量聚合酶链反应（qRT-PCR）用于验证 HCC 组织样本中雌激素相关基因的过表达。
ERGPS 是影响 HCC 患者预后的独立危险因素，在预测患者生存和免疫治疗反应方面优于其他临床变量。多个独立的外部数据集证实了预后特征的优越预测效果。该预后特征与 TMB 评分、MSI 评分、TCR 丰富度、BCR 丰富度、SNV 新抗原评分、CTA 评分、免疫检查点相关基因表达水平和 TIDE 评分呈正相关。通过预后特征确定的高风险组 HCC 患者更有可能对免疫治疗有反应，更适合免疫治疗。qRT-PCR 证实了构建特征的雌激素相关基因在 HCC 肿瘤组织中高表达。
雌激素相关基因在 HCC 组织中过度表达。我们的新预后特征不仅可以准确预测 HCC 患者的预后，还可以预测其免疫治疗反应。在未来，预后特征将成为临床医生筛选适合免疫治疗的 HCC 患者的有用工具。
Zotero 插件
