FANCD2 作为一种新型的预后生物标志物，与乙型肝炎相关肝细胞癌的免疫治疗和药物治疗相关。
FANCD2 as a novel prognostic biomarker correlated with immune and drug therapy in Hepatitis B-related hepatocellular carcinoma.
机构信息
Department of Gastroenterology, the Affiliated Hospital of Southwest Medical University, Luzhou, China.
Department of Gastroenterology, the People's Hospital of Lianshui, Huaian, China.
出版信息
Eur J Med Res. 2023 Oct 11;28(1):419. doi: 10.1186/s40001-023-01411-0.
BACKGROUND
Ferroptosis is related to the immunosuppression of tumors and plays a critical role in cancer progression. Fanconi anemia complementation group D2 (FANCD2) is a vital gene that regulates ferroptosis. However, the mechanism of action of FANCD2 in Hepatitis B-related hepatocellular carcinoma (HCC) remains unknown. In this study, we investigated the prognostic significance and mechanism of action of FANCD2 in Hepatitis B-related HCC.
METHODS
The expression of FANCD2 in Hepatitis B-related HCC was explored using The Cancer Genome Atlas (TCGA) and validated using the Gene Expression Omnibus (GEO) database. Univariate and multivariate Cox regression analyses and Kaplan-Meier survival curves were used to analyze the relationship between FANCD2 expression and the overall survival of patients with Hepatitis B-related HCC. Protein-protein interaction networks for FANCD2 were built using the STRING website. In addition, correlations between FANCD2 expression and the dryness index, tumor mutational burden, microsatellite instability (MSI), immune pathways, genes involved in iron metabolism, and sorafenib chemotherapeutic response were analyzed.
RESULTS
Our results indicated that FANCD2 was significantly overexpressed in Hepatitis B-related HCC and demonstrated a strong predictive ability for diagnosis (Area Under Curve, 0.903) and prognosis of the disease. High FANCD2 expression was associated with poor prognosis, high-grade tumors, high expression of PDL-1, high MSI scores, and low sorafenib IC50 in Hepatitis B-related HCC. BRCA1, BRCA2, FAN1, and FANCC were vital proteins interacting with FANCD2. The expression level of FANCD2 significantly correlated with the infiltration levels of Treg cells, B cells, CD8 + T cells, CD4 + T cells, neutrophils, macrophages, myeloid dendritic cells, and NK cells in Hepatitis B-related HCC. FANCD2 was positively correlated with the tumor proliferation signature pathway, DNA repair, and cellular response to hypoxia.
CONCLUSION
Our study indicated that FANCD2 was a potential novel biomarker and immunotherapeutic target against Hepatitis B-related HCC, which might be related to the chemotherapeutic response to sorafenib.
背景
铁死亡与肿瘤的免疫抑制有关，在癌症进展中起着关键作用。范可尼贫血互补组 D2（FANCD2）是一种重要的基因，它调节铁死亡。然而，FANCD2 在乙型肝炎相关肝细胞癌（HCC）中的作用机制尚不清楚。在本研究中，我们研究了 FANCD2 在乙型肝炎相关 HCC 中的预后意义和作用机制。
方法
使用癌症基因组图谱（TCGA）和基因表达综合数据库（GEO）数据库探讨乙型肝炎相关 HCC 中 FANCD2 的表达情况。采用单因素和多因素 Cox 回归分析及 Kaplan-Meier 生存曲线分析 FANCD2 表达与乙型肝炎相关 HCC 患者总生存期的关系。使用 STRING 网站构建 FANCD2 的蛋白质-蛋白质相互作用网络。此外，分析 FANCD2 表达与干燥指数、肿瘤突变负担、微卫星不稳定性（MSI）、免疫途径、铁代谢相关基因和索拉非尼化疗反应的相关性。
结果
结果表明，FANCD2 在乙型肝炎相关 HCC 中明显过表达，对疾病的诊断（曲线下面积，0.903）和预后具有很强的预测能力。高 FANCD2 表达与预后不良、高级别肿瘤、PDL-1 高表达、MSI 评分高、索拉非尼 IC50 低有关。BRCA1、BRCA2、FAN1 和 FANCC 是与 FANCD2 相互作用的重要蛋白质。FANCD2 的表达水平与乙型肝炎相关 HCC 中 Treg 细胞、B 细胞、CD8+T 细胞、CD4+T 细胞、中性粒细胞、巨噬细胞、髓样树突状细胞和 NK 细胞的浸润水平显著相关。FANCD2 与肿瘤增殖特征途径、DNA 修复和细胞对缺氧的反应呈正相关。
结论
本研究表明，FANCD2 可能是乙型肝炎相关 HCC 的一种潜在的新型生物标志物和免疫治疗靶点，可能与索拉非尼的化疗反应有关。
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