Li Shizhe, Wang Xiaotong, Xiao Junbo, Yi Jun
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Changsha, 410008, Hunan, China.
Eur J Med Res. 2025 Mar 12;30(1):161. doi: 10.1186/s40001-025-02411-y.
This study sought to establish a risk score signature based on disulfidptosis-related genes (DRGs) to predict the prognosis of hepatocellular carcinoma (HCC) patients.
The expression data of DRGs from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) was analyzed to develop and validate a DRG prognostic signature (DRGPS). In vitro, experiments were conducted to explore DRG expressions and roles in HCC tissues and cell lines. HCC tissue microarrays were employed to analyze SLC7A11 expression and its association with clinicopathological characteristics.
The DRGPS consisted of 5 DRGs (SLC7A11, MATN3, CLEC3B, CCNJL, and PON1). The survival rate of HCC patients in high-risk group was significantly lower than that in low-risk group. The DRGPS was also associated with the modulation of tumor microenvironment (TME), tumor mutation burden (TMB), stemness and chemosensitivity. Furthermore, pan-cancer analysis suggested that the DRGPS risk score was associated with immune infiltration and stemness in multiple cancers. Moreover, our DRGPS had potential for predicting treatment efficacy in HCC patients. Finally, we confirmed that downregulation of SLC7A11, a DRG, inhibited the proliferation and migration of HCC cells, while its high expression correlated with advanced TNM clinical stage and larger tumor size.
This study systematically describes a novel DRGPS constructed for predicting HCC prognosis, providing a new approach to risk stratification and treatment options. It also investigates the expression and function of SLC7A11, contributing to further exploration of the molecular mechanism underlying disulfidptosis in HCC, as well as its prognostic and therapeutic implications.
本研究旨在建立基于二硫键连接蛋白相关基因（DRGs）的风险评分特征，以预测肝细胞癌（HCC）患者的预后。
分析来自癌症基因组图谱（TCGA）和国际癌症基因组联盟（ICGC）的DRGs表达数据，以开发和验证DRG预后特征（DRGPS）。在体外，进行实验以探索DRGs在HCC组织和细胞系中的表达及作用。使用HCC组织芯片分析溶质载体家族7成员11（SLC7A11）的表达及其与临床病理特征的关联。
DRGPS由5个DRGs（SLC7A11、基质金属蛋白酶和肌腱蛋白3（MATN3）、C型凝集素结构域家族3成员B（CLEC3B）、细胞周期蛋白J样蛋白（CCNJL）和对氧磷酶1（PON1））组成。高危组HCC患者的生存率显著低于低危组。DRGPS还与肿瘤微环境（TME）的调节、肿瘤突变负荷（TMB）、干性和化疗敏感性相关。此外，泛癌分析表明，DRGPS风险评分与多种癌症的免疫浸润和干性相关。而且，我们的DRGPS具有预测HCC患者治疗疗效的潜力。最后，我们证实，作为一种DRG的SLC7A11的下调抑制了HCC细胞的增殖和迁移，而其高表达与晚期TNM临床分期和更大的肿瘤大小相关。
本研究系统地描述了一种用于预测HCC预后的新型DRGPS，为风险分层和治疗选择提供了一种新方法。它还研究了SLC7A11的表达和功能，有助于进一步探索HCC中二硫键连接蛋白化的分子机制及其预后和治疗意义。
