Paired Normal Liver Tissues Research Articles

Association between F-box-only protein 43 overexpression and hepatocellular carcinoma pathogenesis and prognosis.

Despite great advances in the prevention, diagnosis, treatment, and management regarding hepatocellular carcinoma (HCC), the overall prognosis of HCC remains unfavorable. The expression profile, prognostic role, and biological functions of F-box-only protein 43 (FBXO43) in HCC remain unclear. Here, we determine the expression profile and prognostic value of FBXO43 in patients with HCC. A total of 467 HCC patients and their clinicopathological data were collected from the Second Affiliated Hospital of Jiaxing University, the Cancer Genome Atlas (TCGA), and Genotype-Tissue Expression (GTEx) databases. The expression profile, prognostic value, biological functions, and underlying mechanism of its involvement of FBXO43 were explored based on TCGA, Gene Expression Omnibus (GEO), LinkedOmics, and Cancer Dependency Map (DepMap). The expression of FBXO43 in 93 paired liver tissues was investigated via immunohistochemical staining, tissue microarray analysis, and Western blot. The prognostic value was assessed using survival analysis. FBXO43 RNA was upregulated in HCC liver tissues and was associated with an unfavorable prognosis (p < 0.05). Furthermore, FBXO43 protein was overexpressed in HCC liver tissues compared with that in paired normal liver tissues. Overexpression of FBXO43 protein was significantly associated with advanced TNM stage, large tumor size, lymphatic invasion, distant metastasis, earlier cancer recurrence, and decreased overall survival after radical surgery (p < 0.05). Cox regression analysis showed that FBXO43 had significant prognostic value in HCC. Importantly, FBXO43 and its co-expressed genes were mainly involved in cell cycle regulation, DNA replication, metabolic regulation, and so on. FBXO43 knockdown could significantly affect the HCC cell lines growth and proliferation. We first revealed that FBXO43 was overexpressed in liver HCC tissues at the RNA and protein levels and served as an independent prognostic factor for HCC patients. Therefore, FBXO43 is worth investigating as a potential HCC treatment target.

Characterization of hsa_circ_0000594 as a new biomarker and therapeutic target for hepatoblastoma.

Various studies have shown that aberrant expression of circular RNAs (circRNAs) has a pivotal role in multifarious cancers. However, the role of circRNAs in hepatoblastoma (HB) is not clearly understood. In the present study, we attempted to explore the underlying mechanism of hsa_cric_0000594 in HB along with its clinical importance. In our research, the expression pattern of hsa_circ_0000594 in HB tissues and matched normal liver tissues was determined by in situ hybridization and RT-qPCR. Proliferation, viability, migration, and apoptosis of HB cell lines were detected via Cell Counting Kit-8 (CCK-8), colony formation, transwell, and flow cytometry assays. The interaction of hsa_circ_0000594 with miR-217 was investigated by Dual-Luciferase reporter assay. Expression levels of hsa_circ_0000594 were significantly upregulated in HB tissues compared with those in paired normal liver tissues and showed a clear association with the subtype of HB. The knockdown of hsa_circ_0000594 inhibited the malignant phenotype of HB. Bioinformatics analysis suggests that sirtuin 1 (SIRT1) may serve as a target gene of miR-217. Mechanically, hsa_circ_0000594 was identified to have a critical role in HB development through the hsa_circ_0000594/mir-217/SIRT1 regulatory axis, which might become a novel diagnostic marker and potential therapeutic target in HB.

Integrator complex subunit 6 (INTS6) inhibits hepatocellular carcinoma growth by Wnt pathway and serve as a prognostic marker

BackgroundIntegrator complex subunit 6 (INTS6) was found to play a tumour suppressing role in certain types of solid tumours. In this study, we wanted to determine the expression level of INTS6 in hepatocellular carcinoma (HCC) and evaluate its clinical characteristics and mechanisms in HCC patients (Lui and Lu, European Journal of Cancer, 51:S94, 2015).MethodsFirst, we used a microarray analysis to explore the mRNA expression levels in HCC and paired normal liver tissues; second, we used qRT-PCR to measure the INTS6 mRNA levels in a cohort of 50 HCC tissues and adjacent normal liver tissues; third, we used Western blot analyses to detect the INTS6 protein levels in 20 paired HCC and normal liver tissues; fourth, we used immunohistochemistry to determine the INTS6 expression levels in 70 archived paraffin-embedded HCC samples. Finally, we investigated the suppressive function of INTS6 in the Wnt pathway.ResultsHerein, according to the microarray data analysis, the expression levels of INTS6 were dramatically down-regulated in HCC tissues vs. those in normal liver tissues (p<0.05). qRT-PCR and Western blot analyses showed that the INTS6 mRNA and protein expression was significantly down-regulated in tumour tissues compared to the adjacent normal liver tissues (p<0.05). Immunohistochemical assays revealed that decreased INTS6 expression was present in 62.9% (44/70) of HCC patients. Correlation analyses showed that INTS6 expression was significantly correlated with serum alpha-fetoprotein levels (AFP, p =0.004), pathology grade (p =0.005), and tumour recurrence (p =0.04). Kaplan-Meier analysis revealed that patients with low INTS6 expression levels had shorter overall and disease-free survival rates than patients with high INTS6 expression levels (p =0.001 and p =0.001). Multivariate regression analysis indicated that INTS6 was an independent predictor of overall survival and disease-free survival rates. Mechanistically, INTS6 increased WIF-1 expression and then inhibited the Wnt/β-catenin signalling pathway.ConclusionThe results of our study show that down-regulated INTS6 expression is associated with a poorer prognosis in HCC patients. This newly identified INTS6/WIF-1 axis indicates the molecular mechanism of HCC and may represent a therapeutic target in HCC patients.