Department of General Surgery, Hangzhou Traditional Chinese Medicine (TCM) Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, China.
Front Endocrinol (Lausanne). 2022 Jun 6;13:884777. doi: 10.3389/fendo.2022.884777. eCollection 2022.
Hepatocellular carcinoma (HCC) is a global health challenge with an increasing incidence worldwide. Cancer-associated fibroblasts (CAFs) function critically in HCC initiation and development. However, the prognostic significance of CAF-related gene signatures in HCC remains unknown. Therefore, the specific functions of CAF-related genes in HCC were investigated to help develop potential therapeutic strategies. In this study, CAF-related genes were screened from three CAF-related gene sets. HCC data from the Gene Expression Omnibus (GEO) database was applied to verify the screened CAF-related genes. Cluster analysis was used to identify clusters based on the expression pattern of CAF-related genes and two identified clusters were found to have a significant difference in overall survival (OS) and progression free intervals (PFI). The prognosis of HCC patients was predicted using the prognostic risk score model developed based on HCC data from The Cancer Genome Atlas (TCGA) databases. High-risk group patients had a worse OS than those in low-risk group in TCGA. These results were validated in International Cancer Genome Consortium (ICGC) database. Moreover, combining the clinicopathological characteristics related to prognosis with the model, a nomogram was built for a more accurate prediction of OS of HCC patients. In addition, analyses of immune infiltration characteristics of tumor microenvironment (TME), chemosensitivity, and immunotherapy response were conducted to further evaluate the prognostic value of CAF-related genes. Patients with low-risk scores were found to have higher chemosensitivity to cisplatin, doxorubicin, and sorafenib. Individuals with high-risk scores were found with a higher expression of most immune checkpoints which indicated patients with high-risk scores may benefit more from treatment with immune checkpoint inhibitors. Furthermore, a correlation between immune infiltration characteristics of TME and patients with different risk levels was found. These findings provide a possibility for the further development of personalized treatments in HCC.
肝细胞癌（HCC）是一个全球性的健康挑战，其发病率在全球范围内呈上升趋势。癌相关成纤维细胞（CAF）在 HCC 的发生和发展中起着至关重要的作用。然而，CAF 相关基因特征在 HCC 中的预后意义尚不清楚。因此，研究 CAF 相关基因在 HCC 中的具体功能，有助于开发潜在的治疗策略。本研究从三个 CAF 相关基因集筛选 CAF 相关基因。应用基因表达综合数据库（GEO）数据库中的 HCC 数据验证筛选出的 CAF 相关基因。聚类分析根据 CAF 相关基因的表达模式对 HCC 数据进行聚类分析，发现两个聚类在总生存期（OS）和无进展间隔（PFI）上有显著差异。基于 TCGA 数据库中的 HCC 数据，建立预后风险评分模型预测 HCC 患者的预后。高危组患者的 OS 明显差于 TCGA 中的低危组。这些结果在国际癌症基因组联盟（ICGC）数据库中得到了验证。此外，结合与预后相关的临床病理特征，构建了列线图，以更准确地预测 HCC 患者的 OS。此外，还对肿瘤微环境（TME）的免疫浸润特征、化疗敏感性和免疫治疗反应进行了分析，以进一步评估 CAF 相关基因的预后价值。低危评分患者对顺铂、阿霉素和索拉非尼的化疗敏感性较高。高危评分患者发现大多数免疫检查点表达较高，这表明高危评分患者可能更受益于免疫检查点抑制剂治疗。此外，还发现 TME 的免疫浸润特征与不同风险水平的患者之间存在相关性。这些发现为 HCC 的个体化治疗的进一步发展提供了可能性。
