Introduction: The most common liver disease is nonalcoholic fatty liver disease, characterized by an intrahepatic accumulation of lipids that most often accompanies obesity. Fatty liver can evolve, in the presence of oxidative stress and inflammation, into disabling and deadly liver diseases such as cirrhosis, hepatocellular carcinoma (HCC), and cholangiocarcinoma (CC). Old age seems to favor HCC and CC, in agreement with the inflammaging theory, according to which aging accrues inflammation. Cancer, in general, is an age-related disease, as incidence and mortality for most types of cancer increase with age. However, how molecular drivers in tumors differ or are mutated more frequently among patients of different ages remains scarcely investigated. A recent integrative analysis of the age-associated multi-omic landscape across cancers and healthy tissues demonstrated that age-related gene expression changes are linked to numerous biological processes. HCC and CC have among the lowest five-year survival estimates due to their aggressive progression. Materials and methods: In this study, we extracted top gene candidates from the above-mentioned pan-analyses (i.e., B2M, C1qA, SUCLG1) and tested by qPCR their expression and their correlation with disease progression in 48 tissue samples covering liver disease stages (fatty liver, hepatitis, cirrhosis, HCC and CC) and normal tissues. Results: Here, we report a significant downregulation in the expression of the age-associated gene SUCLG1 during the progression of liver disease toward HCC and CC, which also associates with poor patient survival. Conclusion: SUCGL1, a mitochondrial enzyme gene that catalyzes the conversion of succinyl CoA to succinate, might be therapeutically targeted for the development and progression of age-associated liver cancers with low survival rates.
引言：非酒精性脂肪性肝病是最常见的肝脏疾病，其特征为肝内脂质积聚，通常伴随肥胖发生。在氧化应激和炎症作用下，脂肪肝可进展为肝硬化、肝细胞癌（HCC）及胆管癌（CC）等致残性与致死性肝脏疾病。高龄似乎是HCC和CC的促进因素，这与炎症衰老理论相吻合——该理论认为衰老会累积炎症反应。总体而言，癌症是一种年龄相关性疾病，大多数癌症类型的发病率和死亡率随年龄增长而上升。然而，关于不同年龄段患者肿瘤分子驱动因素的差异性或高频突变特征，目前仍缺乏深入研究。近期一项针对癌症与健康组织年龄相关多组学景观的综合分析表明，年龄相关基因表达变化与众多生物学过程存在关联。HCC和CC因其侵袭性进展特征，五年生存率位列所有癌症中最低的五种之一。材料与方法：本研究从上述泛癌分析中筛选出关键候选基因（即B2M、C1qA、SUCLG1），通过qPCR技术检测48例涵盖肝脏疾病各阶段（脂肪肝、肝炎、肝硬化、HCC及CC）及正常组织的样本中这些基因的表达水平及其与疾病进展的相关性。结果：本研究发现年龄相关基因SUCLG1在肝脏疾病向HCC和CC进展过程中表达显著下调，且与患者不良生存预后相关。结论：线粒体酶基因SUCGL1（催化琥珀酰辅酶A转化为琥珀酸）可能成为治疗低生存率年龄相关性肝癌发生发展的潜在靶点。
Downregulation of Aging-Associated Gene SUCLG1 Marks the Aggressiveness of Liver Disease
肿瘤(癌症)患者之家