Bioinformatics Analysis Identifies ASCL1 as the Key Transcription Factor in Hepatocellular Carcinoma Progression.

Methods: Differentially transcription factors (DETFs) were identified from differentially expressed genes (DEGs) in GSE62232 and transcription factors. Then, they were analyzed by regulatory networks, prognostic risk model, and overall survival analyses to identify the key DETF. Combined with the regulatory networks and binding site analysis, the target mRNA of key DETF was determined, and its prognostic value in HCC was evaluated by survival, clinical characteristics analyses, and experiments. Finally, the expressions and functions of the key DETF on the DEmRNAs were investigated in HCC cells. Results: Through multiple bioinformatics analyses, ASCL1 was identified as the key DETF, and SLC6A13 was predicted to be its target mRNA with the common binding site of CCAGCAACTGGCC, both downregulated in HCC. In survival analysis, high SLC6A13 was related to better HCC prognosis, and SLC6A13 was differentially expressed in HCC patients with clinical characteristics. Furthermore, cell experiments showed the mRNA expressions of ASCL1 and SLC6A13 were both reduced in HCC, and their overexpressions suppressed the growth, invasion, and migration of HCC cells. Besides, over-ASCL1 could upregulate SLC6A13 expression in HCC cells. Conclusion: This study identifies two suppressor genes in HCC progression, ASCL1 and SLC6A13, and the key transcription factor ASCL1 suppresses HCC progression by targeting SLC6A13 mRNA. They are both potential treatment targets and prognostic biomarkers for HCC patients, which provides new clues for HCC research.

Overexpressed Histocompatibility Minor 13 was Associated with Liver Hepatocellular Carcinoma Progression and Prognosis.

Among primary liver carcinoma cases, the proportion of liver hepatocellular carcinoma (LIHC) cases is 75%-85%. Current treatments for LIHC include chemotherapy, surgical excision, and liver transplantation, which are effective for early LIHC treatment. Nevertheless, the early symptoms of liver carcinoma are atypical, so a large proportion of LIHC patients are diagnosed at an advanced stage. Histocompatibility minor 13 (HM13), located in the endoplasmic reticulum, is responsible for catalysing the hydrolysis of some signal peptides after cleavage from the precursor protein. Here, we studied the role of HM13 in LIHC development through bioinformatics analysis. Database analysis showed that HM13 was of great significance for LIHC tumorigenesis. Compared to normal liver tissues, HM13 expression was increased to a greater extent in LIHC tissues. After analysis of Kaplan‒Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA) datasets, we discovered that highly expressed HM13 exhibited an association with shorter overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS). We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses to analyse HM13-related genes, and the data indicated that these genes obviously participated in rRNA processing, ribosome biogenesis, spliceosome, Huntington's disease, and ATP-dependent helicase activity. The Cell Counting Kit-8 (CCK-8) assay and Transwell assay showed that reducing HM13 expression hindered LIHC cell proliferation, migration, and invasion. In conclusion, these findings indicate that HM13 is a biomarker and is related to the poor prognosis of LIHC. Our results are conducive to discovering new targets for LIHC treatment.

Mechanism Analysis of LINC00665 and Its Peptides CIP2A-BP in Hepatocellular Carcinoma.

Background: More and more studies show that long non-coding RNAs (lncRNAs) have miniature open reading frames that can be translated into short peptides. Here, we identify the long non-coding gene LINC00665 and its short peptides (CIP2A-BP) in hepatocellular carcinoma (HCC) and explore how they contribute to HCC progression. Materials and methods: First, GSE101728 data were acquired through the Gene Expression Omnibus for identification of differentially expressed genes (DEGs), and gene set enrichment analysis (GSEA) was conducted to find enriched biological pathways. Then, further bioinformatics analysis was carried out on the screened long non-coding genes, and LINC00665 expression was detected in HCC and normal liver samples. The relations between LINC00665 expression, HCC prognosis, and clinical characteristics were studied. Receiver operating characteristic (ROC) analysis was also applied to verify the LINC00665 prediction in HCC prognosis. In addition, pertinent experiments on LINC00665 and CIP2A-BP were also carried out to explore their roles in the progression of HCC. Results: As a result, we screened out 332 DEGs in total, including 130 upregulated and 202 downregulated DEGs. These DEGs were mainly enriched in posttranscriptional regulation of gene expression, RNA processing, nucleolus, and gene silencing biological pathways. In addition, we found that LINC00665 was increased in HCC samples, which substantially indicated its poor prognosis. Compared with normal tissues, LINC00665 had higher expression in the pathological stages III and IV, tumor-free groups, people no more than 60 years old, and stages T3, T4, N0, N1, and M1. ROC curve indicated that the variable INC00665 had certain accuracy in predicting overall survival (OS). Moreover, in functional experiments, LINC00665 knockdown could significantly decrease HCC cell proliferation, migration, and invasion, while overexpressed CIP2A-BP could markedly increase HCC cell proliferation, invasion, and migration. Conclusion: Our findings not only disclose a unique mechanism by which CIP2A-BP encoded by LINC00665 promotes HCC carcinogenesis but suggest that these long non-coding genes and short peptides could be used as biomarkers for HCC diagnosis and prognosis and new targets for HCC therapy.

Association Between Procalcitonin and Post-hepatectomy Liver Failure in Hepatocellular Carcinoma Patients.

Objectives: Procalcitonin (PCT) has long been proved as an early diagnostic signal for postoperative outcomes. The purpose of this study is to explore the value of serum procalcitonin levels in predicting post-hepatectomy liver failure (PHLF), and further to declarethe relationship between postoperative PCT and short-term prognosis in patients after hepatectomy. Methods: Clinical data of patients with hepatocellular carcinoma (HCC) who underwent hepatectomy from June 1st, 2019 to September 31st, 2020 at Shanghai Eastern Hepatobiliary Surgery Hospital had been retrospectively analyzed. Logistic regression analysis was used to evaluate the risk factors related to PHLF. The Kaplan-Meier method was used to calculate the PHLF rate and 30-day survival after surgery. Results: A total of 885 patients with complete data were finally included in analysis, 311 of them with elevated serum PCT (≥1 ng/ml). Results of the logistic regression analysis suggested a significant association between PCT and PHLF [HR, 95%CI; 3.801 (1.825, 7.917), p < 0.001]. Other significant risk factors for PHLF included portal hypertension, portal blocking time (>30 min) and blood transfusion (>200 ml). Kaplan-Meier analysis also suggested a higher PHLF rate in elevated PCT patients [9.0% (95% CI, 7.3 to 12.8 VS. 1.9% (95% CI, 1.1-4.3)); p < 0.001]. For secondary outcomes, elevated PCT was also highly associated with postoperative sepsis, ICU admission, 30-day mortality and 3-month mortality. Conclusion: Elevated procalcitonin level in patients after hepatectomy is related to higher PHLF rate, with lower 30-day survival and poor short-term postoperative outcomes.