The role of BCL9 genetic variation as a biomarker for hepatitis C-related hepatocellular carcinoma in Egyptian patients

Abstract Background Hepatocellular carcinoma (HCC) is considered one of the most common cancers related to mortality around the world, and susceptibility is related with genetic, lifestyle, and environmental factors. Copy number variation of the Bcell CLL/lymphoma 9 (BCL9) gene is a type of structural variation which can influence gene expression and can be related with specific phenotypes and diseases and has a role in hepatocarcinogenesis. Our aims were to assess the copy number variation (CNV) in the BCL9 gene and explore its role in HCV-related HCC Egyptian patients. A total of 50 HCV-related HCC patients were enrolled in the study (including 25 early HCC and 25 late HCC cases); the copy number of the BCL9 gene was detected using quantitative polymerase reaction. Results There was a highly statistically significant difference between the two groups (early and late HCC patients) in gender, bilharziasis, performance status, child score class, child grade, focal lesion size, portal vein, and ascites. CNV was detected and represented by the gain in the BCL9 gene in 14% of patients, and all of them were males. Also, it was noticed that the ratio of gain in BCL9 copy number in late individuals was about 1.5 times than that in early HCC individuals. Moreover, our results showed that the distribution of performance status > 1, average and enlarged liver, focal lesion size, thrombosed portal vein, and AFP was higher in patients with BCL9 copy number gain. Conclusion We detected about 14% gain in BCL9 copy number in Egyptian HCC patients. But the variation in copy number of the BCL9 gene did not affect HCC development in our patients’ cohort.

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Role of chromosome 1q copy number variation in hepatocellular carcinoma

World Journal of Hepatology ◽

10.4254/wjh.v13.i6.662 ◽

2021 ◽

Vol 13 (6) ◽

pp. 662-672

Author(s):

Nathan R Jacobs ◽

Pamela A Norton

Keyword(s):

Hepatocellular Carcinoma ◽

Copy Number Variation ◽

Copy Number ◽

Chromosome 1Q ◽

Number Variation

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Non-invasive Analysis of Genomic Copy Number Variation in Patients with Hepatocellular Carcinoma by Next Generation DNA Sequencing

Journal of Cancer ◽

10.7150/jca.10747 ◽

2015 ◽

Vol 6 (3) ◽

pp. 247-253 ◽

Cited By ~ 28

Author(s):

Hongtao Xu ◽

Xia Zhu ◽

Zulong Xu ◽

Yue Hu ◽

Shiping Bo ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Copy Number Variation ◽

Dna Sequencing ◽

Copy Number ◽

Next Generation ◽

Next Generation Dna Sequencing ◽

Non Invasive ◽

Genomic Copy Number ◽

Number Variation ◽

Genomic Copy Number Variation

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AUNIP Expression Is Correlated With Immune Infiltration and Is a Candidate Diagnostic and Prognostic Biomarker for Hepatocellular Carcinoma and Lung Adenocarcinoma

Frontiers in Oncology ◽

10.3389/fonc.2020.590006 ◽

2020 ◽

Vol 10 ◽

Author(s):

Chenxi Ma ◽

Wenyan Kang ◽

Lu Yu ◽

Zongcheng Yang ◽

Tian Ding

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

B Cells ◽

Copy Number Variation ◽

Lung Adenocarcinoma ◽

Copy Number ◽

Prognostic Biomarker ◽

Variation Analysis ◽

Immune Infiltration ◽

Number Variation

AUNIP, a novel prognostic biomarker, has been shown to be associated with stromal and immune scores in oral squamous cell carcinoma (OSCC). Nonetheless, its role in other cancer types was unclear. In this study, AUNIP expression was increased in hepatocellular carcinoma (HCC) and lung adenocarcinoma (LUAD) according to data from The Cancer Genome Atlas (TCGA) database, Integrative Molecular Database of Hepatocellular Carcinoma (HCCDB), and Gene Expression Omnibus (GEO) database (GSE45436, GSE102079, GSE10072, GSE31210, and GSE43458). Further, according to copy number variation analysis, AUNIP up-regulation may be associated with copy number variation. Immunohistochemistry showed AUNIP expression was higher in HCC and LUAD compared with the normal tissues. Receiver operating characteristic (ROC) curve analysis demonstrated that AUNIP is a candidate diagnostic biomarker for HCC and LUAD. Next, TCGA, International Cancer Genome Consortium (ICGC), and GEO (GSE31210 and GSE50081) data showed that increased AUNIP expression clearly predicted poor overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) in HCC and LUAD. Additionally, multivariate Cox regression analysis involving various clinical factors showed that AUNIP is an independent prognostic biomarker for HCC and LUAD. Next, the role of AUNIP in HCC and LUAD was explored via a co-expression analysis, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, and a gene set variation analysis (GSVA). HCC and LUAD exhibited almost identical enrichment results. More specifically, high AUNIP expression was associated with DNA replication, cell cycle, oocyte meiosis, homologous recombination, mismatch repair, the p53 signal transduction pathway, and progesterone-mediated oocyte maturation. Lastly, the Tumor Immune Estimation Resource (TIMER) tool was used to determine the correlations of AUNIP expression with tumor immune infiltration. AUNIP expression was positively correlated with the infiltration degree of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells in HCC. However, AUNIP expression was negatively correlated with the infiltration degree of B cells, CD4+ T cells, and macrophages in LUAD. In addition, AUNIP expression was correlated with immune infiltration in various other tumors. In conclusion, AUNIP, which is associated with tumor immune infiltration, is a candidate diagnostic and prognostic biomarker for HCC and LUAD.

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