Electronic Journal of Liver Tumor

Clinical significance and functional analysis of NADH: ubiquinone oxidoreductase complex assembly factor 2 in liver cancer

Zhu Ying, Gu Xinglu, Zhao Xiaohang, Sun Yulin

2022, 9(1): 29-35.

Asbtract ( 68 )

PDF (5295KB) ( 4 )

References | Related Articles | Metrics

Objective:To investigate the expression characteristics, clinical and prognostic significance as well as potential functional mechanisms of NADH: ubiquinone oxidoreductase complex assembly factor 2 (NDUFAF2) in liver cancer based on multi-omics data from The Cancer Genome Atlas (TCGA) database.
Method:RNA sequencing, whole exome sequencing, single nucleotide polymorphism microarray and DNA methylation sequencing data of TCGA liver cancer samples were used to analyze the expression characteristics and possible causes for abnormally high expression of NDUFAF2 in liver. The highly correlated co-expressed genes with NDUFAF2 were used to perform the pathways and human phenotype enrichment analyses, and then the functional network was constructed using Cytoscape software.
Result:Expression and survival analysis based on RNA sequencing data from liver cancer patients of TCGA showed that among all subunits of the mitochondrial respiratory complexes, only NDUFAF2 was significantly overexpressed in tumor tissues and correlated with unfavorable overall survival and recurrence-free survival. Elevated expression of NDUFAF2 was associated with gender, race, tumor differentiation and microvascular invasion (all P<0.05). Copy number gain, TP53 and CTNNB1 missense mutation as well as MYC amplification but not promoter methylation were all responsible for high NDUFAF2 expression in tumor. The enrichment analysis of 411 genes that co-expressed with NDUFAF2 revealed that NDUFAF2 may contribute to hepatocarcinogenesis by regulating cellular energy production, oxidative stress, RNA processing, protein translation and c-Myc and mTORC1-related pathways.
Conclusion:Elevated expression of NDUFAF2 in liver cancer maybe engage in carcinogenesis by facilitating RNA processing, protein translation and intracellular signaling pathways. NDUFAF2 can serve as a potential prognostic marker and a new target for therapeutic intervention for liver cancer.

Role of BAI1 gene in anti-angiogenesis of hepatic carcinoma

Zhu Qing, Wei Zhewen, Wang Xiaobing, Cai Jianqiang

2022, 9(1): 36-40.

Asbtract ( 74 )

PDF (4758KB) ( 10 )

References | Related Articles | Metrics

Objective:To explore the role of BAI1 gene in anti-angiogenesis of hepatic carcinoma.
Method:The BAI1 gene knockout PLC/PRF/5 cell line was constructed using CRISPR/Cas9 technology, and the knockout results were verified by Sanger sequencing and Western blotting. The CCK8 method was used to detect the effect of BAI1 gene knockout on the proliferation of liver cancer cell lines. The PLC/PRF/5 cell line was co-cultured with human umbilical vein endothelial cells(HUVEC) to detect the effect of BAI1 gene expression on the ability of cell tube formation. Transplanted tumor model was used to study the effect of BAI1 gene expression on liver cancer growth and tumor angiogenesis in vivo.
Result:Sanger sequencing and Western blotting showed that BAI1 gene was successfully knocked out. The proliferation of PLC/PRF/5 cells was significantly accelerated and the number of tube was increased significantly with BAI1 gene deficiency. The tumor growth was inhibited in vivo with BAI1 gene overexpression, and the positive expression of CD31 was decreased.
Conclusion:The BAI1 gene knockout PLC/PRF/5 cell line was successfully constructed using CRISPR/Cas9 technology. BAI1 gene deficiency promote the proliferation of liver cancer cells and angiogenesis.

Analysis of the expression and prognostic significance of dentideless E3 ubiquitin ligase in hepatocellular carcinoma based on bioinformatics methods

Liu Zhenrong, Xiao Ting

2022, 9(1): 41-47.

Asbtract ( 114 )

PDF (9253KB) ( 14 )

References | Related Articles | Metrics

Objective:To investigate the expression and prognostic value of dentideless E3 ubiquitin ligase (DTL) in hepatocellular carcinoma (HCC).
Method:Transcriptome data of 374 HCC tissues and 50 paracancer tissues were downloaded from The Cancer Genome Atlas (TCGA) database. The GSE121248 dataset was downloaded from the Gene Expression Omnibus (GEO) database, and transcriptome data including 70 HCC tissues and 37 paracancer normal tissues was obtained. The expression level of DTL in HCC tissues was compared with that in normal adjacent tissues. Kaplan-meier method was used for survival analysis, and log-rank test was used to compare the overall survival rate and progression-free interval rate of HCC patients between the DTL high expression group and the DTL low expression group. The risk factors for poor prognosis of HCC patients were analyzed by Cox regression analysis. The receiver operator characteristic (ROC) curve of DTL expression level for HCC diagnosis was plotted. The effect of DTL on the prognosis of HCC patients was predicted by using multivariate Cox regression analysis. Meanwhile, GSEA enrichment analysis was performed for differentially expressed genes in HCC tissues of DTL high expression group and DTL low expression group.
Result:The expression level of DTL in HCC tissues was higher than that in adjacent normal tissues (P<0.001). There were statistically significant differences in age, race, AFP level, histologic grade, pathological stage and T stage between the DTL high expression group and the DTL low expression group (P<0.05). Kaplan-meier survival analysis showed that overall survival and progression-free survival were shorter in HCC patients with high DTL expression compared with HCC patients with low DTL expression (P=0.005, P<0.001). ROC curve showed that DTL expression level had strong diagnostic ability for HCC [area under the curve (AUC) was 0.96]. The c-index of DTL expression was 0.663 (95%CI 0.54~0.61). GSEA enrichment analysis showed that DTL may affect the occurrence and development of HCC through the influence of cell cycle, chromosome maintenance, DNA replication, G2/M checkpoint, mitotic stage, TP53 transcription regulation and other pathways.
Conclusion:High expression of DTL predicts poor prognosis of hepatocellular carcinoma, suggesting that DTL may be a potential biomarker for diagnosis and prognosis of hepatocellular carcinoma.

Study on the mechanism of total glycosides of ranunculus japonicus inhibiting the proliferation, migration and invasion of liver cancer cells through the circ_0079593/miR-324-5p pathway

Du Honglei, Zhang Feng, Zhang Yonghua, Ban Zhichao, Wang Xu

2022, 9(1): 48-54.

Asbtract ( 78 )

PDF (8576KB) ( 20 )

References | Related Articles | Metrics

Objective:To explore the effect of total glycosides of ranunculus japonicus on the proliferation, migration and invasion of liver cancer MHCC97H cells and its regulation of circ_0079593/miR-324-5p pathway.
Method:Human hepatocarcinoma cells MHCC97H were cultured in vitro, experimental groups: control group, total glycosides of ranunculus japonicus low-dose group, total glycosides of ranunculus japonicus medium-dose group, total glycosides of ranunculus japonicus high-dose group, si-NC group, si-circ_0079593 group, total glycosides of ranunculus japonicus+pcDNA group, total glycosides of ranunculus japonicus+pcDNA-circ_0079593 group. CCK-8 and Transwell chamber experiments were used to detect cell viability, migration and invasion. The quantitative reverse transcription polymerase chain reaction (qRT-PCR) method was used to detect the expression of circ_0079593 and miR-324-5p. The dual luciferase reporter gene experiment was used to detect the targeting relationship between circ_0079593 and miR-324-5p. Western blotting was used to detect the protein expression of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9).
Result:Compared with the control group, the cell proliferation inhibition rate and the expression level of miR-324-5p in different dose groups of total glycosides of ranunculus japonicus were increased (P<0.05), while the number of migrating and invading cells was decreased (P<0.05), and the expression level of circ_0079593 and the protein levels of MMP-2, MMP-9 were decreased (P<0.05), and were dose-dependent. circ_0079593 could target and regulate miR-324-5p. Compared with the si-NC group, the cell proliferation inhibition rate in the si-circ_0079593 group was increased (P<0.05), while the number of migrating and invading cells was decreased (P<0.05), and the protein levels of MMP-2 and MMP-9 were decreased (P<0.05). Compared with the total ranunculus glycosides+pcDNA group, the inhibition rate of cell proliferation in the total ranunculus glycosides+pcDNA-circ_0079593 group was reduced (P<0.05), while the number of migration and invasion cells was increased (P<0.05), and the protein levels of MMP-2, MMP-9 were increased (P<0.05).
Conclusion:Total glycosides of ranunculus japonicus could reduce the proliferation, migration and invasion of liver cancer cells by regulating the circ_0079593/miR-324-5p pathway.

Analysis of the incidence and mortality of liver cancer in Gansu cancer registration areas, 2017

Yuan Haoran, Ding Gaoheng, Chen Lili, Liu Yuqin

2022, 9(1): 55-60.

Asbtract ( 91 )

PDF (2454KB) ( 9 )

References | Related Articles | Metrics

Objective:To analyze the incidence and mortality of liver cancer in Gansu Province in 2017, and provide a basis for formulating prevention and treatment strategies for liver cancer.
Method:We collected registration data of cancer incidence, mortality and population data reported by 23 cancer registration points in Gansu Province in 2020, and the data from 10 registration points meet the quality control standards. We calculated the incidence and mortality of liver cancer according to gender, areas (urban and rural) and age groups, and use the standard population composition of China in 2000 and Segi's world standard population age composition to calculate the standardized rate of Chinese population (ASR China) and the standardized rate of world population (ASR World).
Result:In 2017, there were 774 new cases of liver cancer in the cancer registration area of Gansu Province, accounting for 7.90% of all malignant cancers, ranking fifth in the incidence of malignant cancers, with an incidence rate of 23.35/100 000 (male 31.89/100 000, female 14.43/100 000), ASR China was 16.19/100 000, ASR World was 15.95/100 000, and the cumulative rate was 1.87%; the incidence rate in urban areas was 23.25/100 000, and ASR China was 15.20/100 000; in rural areas, the crude incidence rate in the region was 23.55/100 000, and ASR China was 18.91/100 000. In 2017, there were 623 new cases dying from liver cancer in the cancer registration area of Gansu Province, accounting for 12.16% of all cancer deaths ranking third among cancer death profiles, with a mortality rate of 18.80/100 000 (male 25.04/100 000, female 12.27/100 000), ASR China was 13.03/100 000, ASR World was 12.88/100 000, and the cumulative rate was 1.49%; the crude mortality rate in urban areas was 18.94/100 000, and ASR China was 12.29/100 000; The crude mortality rate in rural areas was 18.51/100 000, and ASR China was 15.35/100 000. In 2017, the area with the highest incidence and mortality of liver cancer in the cancer registration area of Gansu Province was Jingtai County.
Conclusion:The incidence and mortality of liver cancer in Gansu Province are still high, and there are regional and gender differences. According to the actual situation and the epidemiological characteristics of liver cancer, health education should be actively carried out, comprehensive prevention and control of liver cancer risk factors should be implemented, and early diagnosis and treatment of liver cancer should be promoted. Taking screening as the starting point, multi-dimensional joint efforts to promote the prevention and control of liver cancer in Gansu Province.

Progress on immune mechanism of traditional Chinese medicine regulating gut microbiota and its metabolites in the occurrence and development of liver cancer

Li Cunya, Fu Shujuan, Li Yun, Zhong Zhixian, Wang Zhiying, Zhong Yi

2022, 9(1): 61-64.

Asbtract ( 132 )

PDF (1896KB) ( 8 )

References | Related Articles | Metrics

Traditional Chinese Medicine plays an indispensable role in the clinical treatment of tumor, especially in comprehensive adjuvant therapy, it can significantly reduce the adverse reactions caused by radiotherapy, chemotherapy, targeted therapy and immunotherapy, collection of treatment and health in one and strengthening healthy to eliminate pathogens. At the same time, the intestinal microflora and its metabolites are regulated to increase beneficial bacteria and reduce harmful bacteria, repair the intestinal microenvironment, regulate bile acid (BA) metabolism and immune factor expression, exert immune response, and then improve the liver regeneration microenvironment to inhibit the occurrence and development of liver cancer. This review will start with the regulation of intestinal flora by traditional Chinese medicine and explain its immune mechanism in liver cancer.

Application status and progress of immune checkpoint inhibitors in liver cancer

Xie Yan, Huang Yabei, Jiang Wentao

2022, 9(1): 65-70.

Asbtract ( 53 )

PDF (1740KB) ( 11 )

References | Related Articles | Metrics

Primary liver cancer is one of the most common malignant tumors and its incidence ranks fourth in the incidence of cancer in China. The progress of liver cancer is rapid and the concealment is strong, and the patients are often in the middle and late stage when they are diagnosed, so they miss the best time for treatment. Since 2007, the advent of sorafinib marks the advent of the era of targeted therapy for liver cancer, but its use is limited by drug resistance and adverse drug reactions. In recent years, the discovery of immune checkpoint provides a new treatment option for patients with advanced liver cancer. Immune checkpoint inhibitor has good efficacy and safety, which makes it a potential research direction in the field of liver cancer treatment.

Table of Content