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Backgroud: In our current work, we aimed to investigate the expressions of glypican (GPC) family genes at the mRNA level and assess their prognostic significances in patients with hepatocellular carcinoma (HCC).Methods: The pathological roles of GPC family genes were examined using bioinformatics analysis. The diagnostic values of GPC genes were explored with the Gene Expression Profiling Interactive Analysis. Moreover, the mRNA expression and prognostic values of GPC genes were assessed via the KM plotter database.Results: Our data showed that the expression of GPC-3 was dramatically increased in the liver tumor tissue. Moreover, the expressions of the other five GPC family members were not significantly different between the tumor and normal liver tissues (P > 0.05). Furthermore, the up-regulation of GPC-1 at the mRNA level was dramatically correlated to the reduced overall survival (OS) for all HCC patients (hazard ratio = 2.03, 95% confidence intervals =1.44-2.87, P = 4.1e-05) compared with its low-expression group. Besides, the prognosis of the Caucasians was related to most GPC family genes, while the prognosis of the Asian race was only related to the expression of GPC-2. Besides, for pathological factors, including stage, grade, AJCC, and vascular invasion, the higher the pathological grade and vascular invasiveness, the lower the expression levels of GPC family genes (P < 0.05). Finally, the expression levels of GPC-1, 2, and 3 in the hepatitis group were related to the poor prognosis of HCC in the risk factor (alcohol consumption and hepatitis) subgroup (P < 0.05).Conclusions: Our findings indicated that GPC-3 was dysregulated in HCC compared with paracancerous tissues. The expression of GPC-1 could be used as a potent predictive index for the general prognosis of HCC. The pathology, patients, and risk factors might affect the prognostic value of GPC family genes in HCC. [ABSTRACT FROM AUTHOR]

Background/Aims. Hepatocellular carcinoma (HCC) is a common malignant tumor with a high rate of recurrence. Immunohistochemical analysis of the marker of proliferation Ki-67 (MKI67) is used to assess proliferation activity of HCC. The regulation of MKI67 expression remains unclear in HCC. This study aims to explore the association between MKI67 expression and gene variants. Methods: A total of 195 hepatitis B virus (HBV)-related HCC patients were genotyped using Illumina HumanExome BeadChip-12-l_A (242,901 markers). An independent cohort (97 subjects) validated the association of polymorphism determinants and candidate genes with MKI67 expression. The relationships between MKI67 with p53 and variants of candidate genes in the clinical outcomes of HCC patients were analyzed. Results: We found that MKI67 combined with p53 was associated with a 3-year recurrence-free survival and five variants near TTN and CCDC8 were associated with MKI67 expression. TTN harboring rs2288563-TT and rs2562832-AA+CA indicated a favorable outcome for HCC patients. Conclusion: Variants near TTN and CCDC8 were associated with MKI67 expression, and rs2288563 and rs2562832 in TTN are potential biomarkers for the prediction of clinical outcomes in HBV-related HCC patients. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) is one of the most prevalent and life-threatening malignancies worldwide. There are few diagnostic and prognostic biomarkers and druggable targets for HCC. Aldehyde dehydrogenase 1 (ALDH1) is a marker of stem cells in a variety of cancers, but the mRNA levels and prognostic value of ALDH1 isoforms in HCC patients remain unknown. In the present study, gene ontology annotation of the ALDH1 family was performed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), and the gene pathway analsis was performed using GeneMANIA software. The initial prognostic value of ALDH1 expression in 360 HCC patients was assessed using the OncoLnc database. The expression levels of ALDH1 isoforms in normal liver tissues and clinical specimens of cancer vs. normal control datasets were determined using the GTEx and Oncomine databases, respectively. We then analyzed the prognostic value of ALDH1 expression in 212 hepatitis B virus (HBV)–related HCC patients using the GEO database. We found that the ALDH1 isoform showed high aldehyde dehydrogenase activity. The ALDH1A1, ALDH1B1, and ALDH1L1 genes encoded for the ALDH1 enzyme. High ALDH1B1 expression had protective qualities in HCC patients. Moreover, HBV–related HCC patients who showed high ALDH1L1 gene expression had a better clinical outcomes. In addition, high ALDH1A1 expression was associated with a 57–month recurrence–free survival in HBV-related HCC patients. High ALDH1B1 expression was protective for HCCs with multiple nodules and high serum alpha–fetoprotein (AFP) level. Furthermore, high serum AFP levels contributed to lower ALDH1L1. ALDH1A1, ALDH1B1, and ALDH1L1, all of which were considered promising diagnostic and prognostic markers as well as potential drug targets. [ABSTRACT FROM AUTHOR]