Prognostic and predicted significance of Ubqln2 in patients with hepatocellular carcinoma.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Neuron-glial antigen 2 overexpression in hepatocellular carcinoma predicts poor prognosis.

AIM: To investigate whether neuron-glial antigen 2 (NG2) could be an effective prognostic marker in hepatocellular carcinoma (HCC). METHODS: NG2 expression was semi-quantitatively scored from the immunohistochemistry (IHC) data based on the number of positive cells and the staining intensity. A total of 132 HCC specimens and 96 adjacent noncancerous tissue samples were analyzed by IHC for NG2 protein expression. To confirm the NG2 expression levels observed by IHC, we measured NG2 expression in 30 randomly selected tumor and adjacent noncancerous tissue samples by quantitative real-time polymerase chain reaction and Western blot. The correlations between NG2 protein expression and the clinicopathological features of HCC patients were analyzed using the χ (2) test. To assess the prognostic value of NG2 for HCC, the association between NG2 expression and survival was analyzed using the Kaplan-Meier method with the log-rank test. To further evaluate the prognostic value of NG2 expression, a Cox multivariate proportional hazards regression analysis was performed with all the variables to derive risk estimates related to disease-free and overall survival and to control for confounders. RESULTS: High NG2 expression was observed in significantly more primary tumor samples (63.6%; 84/132) compared with the adjacent noncancerous tissue samples (28.1%; 27/96) (P < 0.0001). Moreover, high NG2 protein expression was closely associated with tumor differentiation (χ (2) = 9.436, P = 0.0089), recurrence (χ (2) = 5.769, P = 0.0163), tumor-node-metastasis (TNM) stage (χ (2) = 8.976, P = 0.0027), and invasion (χ (2) = 5.476, P = 0.0193). However, no significant relationship was observed between NG2 protein expression in HCC and other parameters, such as age, sex, tumor size, serum alpha fetoprotein (AFP), tumor number, or tumor capsule. The log-rank test indicated a significant difference in the overall survival of HCC patients with high NG2 expression compared with those with low NG2 expression (29.2% vs 9.5%, P < 0.001). Moreover, NG2 expression in HCC tissue significantly correlated with disease-free survival (15.2% vs 6.7%, P < 0.001). Multivariate analysis showed that NG2 expression (HR = 2.035, P = 0.002), serum AFP (HR = 1.903, P = 0.003), TNM stage (HR = 2.039, P = 0.001), and portal vein invasion (HR = 1.938, P = 0.002) were independent prognostic indicators for OS in HCC patients. Furthermore, NG2 expression (HR = 1.974, P = 0.003), serum AFP (HR = 1.767, P = 0.008), TNM stage (HR = 2.078, P = 0.001), tumor capsule (HR = 0.652, P = 0.045), and portal vein invasion (HR = 1.941, P = 0.002) were independent prognostic indicators for DFS in HCC patients. CONCLUSION: The up-regulation of NG2 is associated with poor prognosis in HCC. Therefore, NG2 could be useful as an additional prognostic marker to increase the resolution of traditional approaches.