Key Laboratory of Hepatobiliary and Pancreatic Surgery, Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
School of Medicine, the Southern University of Science and Technology, Shenzhen, Guangdong, China.
Cancer Med. 2020 Jun;9(12):4083-4094. doi: 10.1002/cam4.3040. Epub 2020 Apr 15.
Hepatocellular carcinoma (HCC) is a common malignant cancer and the third leading cause of death worldwide. The molecular mechanism of HCC remains unclear. Recent studies have demonstrated that the ubiquitin-proteasome system (UPS) is associated with HCC. Ubqln2, a member of the UPS, is abnormally expressed in HCC. However, whether Ubqln2 is associated with HCC prognosis remains unknown.
We analyzed the associations between overall survival and various risk factors in 355 HCC tissue samples obtained from the Cancer Genomic Atlas (TCGA) database at the mRNA level and in 166 HCC tissue samples from Southwest Hospital at the protein level. qRCR was used to determinate Ubqln2 expression in cancer and noncancerous tissues. The association between Ubqln2 and Ki-67 was analyzed by immunohistochemistry. The association between Ubqln2 expression and survival was analyzed using Kaplan-Meier curve and Cox proportional hazards models. A nomogram was used to predict the impact of Ubqln2 on prognosis. Mutated genes were analyzed to determine the potential mechanism.
Ubqln2 highly expressed in HCC tissues. The Ubqln2 mRNA level had significant relations with UICC tumor stage (P = .022), UICC stage (P = .034) and resection potential (P = .017). Concordantly, the Ubqln2 protein was closely associated with tumor size (P = .005), UICC stage (P = .012), and recurrence (P = .009). Ubqln2 was highly expressed in HCC and positively associated with poor survival. The nomogram precisely predicted the prognosis of HCC patients with high or low Ubqln2 expression. A genomic waterfall plot suggested that Ubqln2 expression was closely associated with mutated CTNNB1.
Our findings reveal that Ubqln2, an independent risk factor for HCC, is a potential prognostic marker in HCC patients. Ubqln2 expression is positively associated with mutated CTNNB1.
肝细胞癌（HCC）是一种常见的恶性肿瘤，也是全球死亡的第三大主要原因。HCC 的分子机制尚不清楚。最近的研究表明，泛素-蛋白酶体系统（UPS）与 HCC 有关。Ubqln2 是 UPS 的一个成员，在 HCC 中异常表达。然而，Ubqln2 是否与 HCC 预后有关尚不清楚。
我们在 TCGA 数据库中分析了 355 例 HCC 组织样本的总生存率与各种危险因素之间的关系（mRNA 水平），并在西南医院的 166 例 HCC 组织样本中分析了蛋白质水平的关系。qRCR 用于测定癌症和非癌组织中的 Ubqln2 表达。通过免疫组织化学分析 Ubqln2 与 Ki-67 的相关性。Kaplan-Meier 曲线和 Cox 比例风险模型用于分析 Ubqln2 表达与生存之间的关系。使用列线图预测 Ubqln2 对预后的影响。分析突变基因以确定潜在机制。
Ubqln2 在 HCC 组织中高表达。Ubqln2 mRNA 水平与 UICC 肿瘤分期（P=0.022）、UICC 分期（P=0.034）和切除潜能（P=0.017）显著相关。一致地，Ubqln2 蛋白与肿瘤大小（P=0.005）、UICC 分期（P=0.012）和复发（P=0.009）密切相关。Ubqln2 在 HCC 中高表达，并与不良生存相关。列线图精确预测了 Ubqln2 高或低表达的 HCC 患者的预后。基因组瀑布图表明 Ubqln2 表达与突变型 CTNNB1 密切相关。
我们的研究结果表明，Ubqln2 是 HCC 的一个独立危险因素，是 HCC 患者潜在的预后标志物。Ubqln2 表达与突变型 CTNNB1 呈正相关。
