Luo Wenqi, Wu Shu, Zhang Fengyou, Chen Xiaoyu, Ma Yun, Mo Yingxi
Department of Pathology, Guangxi Medical University Cancer Hospital, Nanning, China.
Key Laboratory of High-Incidence-Tumor Prevention & Treatment (Guangxi Medical University), Ministry of Education, Nanning, China.
Pathol Res Pract. 2022 Oct;238:154111. doi: 10.1016/j.prp.2022.154111. Epub 2022 Sep 6.
Growing evidence indicates that altered metabolism represents the hallmark of hepatocellular carcinoma (HCC). The mitochondrial 3-hydroxybutyrate dehydrogenase 1 (BDH1) is a key catalytic enzyme in ketogenesis with unknown roles in HCC. Hundred and four tissue sample pairs (HCC tissues, n = 104; matched normal tissues, n = 104) were obtained and analyzed with immunohistochemical (IHC) staining to investigate the clinical and functional role and the diagnostic and prognostic value of BDH1 in HCC. In addition, RNA-Seq datasets from the Tumor Immune Estimation Resource (TIMER) (HCC group, n = 371; normal group, n = 50) and microarray datasets from the Gene Expression Omnibus (GEO) database (HCC tissues, n = 1671; normal tissues, n = 1479) were used to assess BDH1 expression in HCC. Several bioinformatic methods were performed to identify pathways regulated by BDH1. The IHC staining showed that BDH1 expression decreased in HCC tissues (n = 69) compared with that in adjacent normal tissues (n = 35, P < 0.001). Low BDH1 expression was associated with advanced clinical stage (P = 0.033) and vascular invasion (P = 0.007). Moreover, ectopic expression of BDH1 reduced tumor proliferation and suppressed the migration and invasion of HCC cells in vitro. Therefore, our data suggest that BDH1 is a potentially valuable diagnostic biomarker and therapeutic target for HCC.
越来越多的证据表明，代谢改变是肝细胞癌（HCC）的标志。线粒体3-羟基丁酸脱氢酶1（BDH1）是生酮过程中的关键催化酶，其在HCC中的作用尚不清楚。本研究获取了104对组织样本（HCC组织，n = 104；配对的正常组织，n = 104），并通过免疫组织化学（IHC）染色进行分析，以研究BDH1在HCC中的临床和功能作用以及诊断和预后价值。此外，还使用了来自肿瘤免疫评估资源（TIMER）的RNA测序数据集（HCC组，n = 371；正常组，n = 50）和来自基因表达综合数据库（GEO）的微阵列数据集（HCC组织，n = 1671；正常组织，n = 1479）来评估BDH1在HCC中的表达。采用多种生物信息学方法来鉴定受BDH1调控的通路。IHC染色显示，与相邻正常组织（n = 35）相比，HCC组织（n = 69）中BDH1表达降低（P < 0.001）。BDH1低表达与临床晚期（P = 0.033）和血管侵犯（P = 0.007）相关。此外，BDH1的异位表达降低了肿瘤增殖，并在体外抑制了HCC细胞的迁移和侵袭。因此，我们的数据表明BDH1是一种潜在有价值的HCC诊断生物标志物和治疗靶点。
