Abstract
BackgroundHepatocellular carcinoma (HCC) is the most common type of liver cancer that occurs predominantly in patients with previous liver conditions. In the absence of an ideal screening modality, HCC is usually diagnosed at an advanced stage. Recent studies show that loss or gain of genomic materials can activate the oncogenes or inactivate the tumor suppressor genes to predispose cells toward carcinogenesis. Here, we evaluated both the copy number alteration (CNA) and RNA sequencing data of 361 HCC samples in order to locate the frequently altered chromosomal regions and identify the affected genes.ResultsOur data show that the chr1q and chr8p are two hotspot regions for genomic amplifications and deletions respectively. Among the amplified genes, YY1AP1 (chr1q22) possessed the largest correlation between CNA and gene expression. Moreover, it showed a positive correlation between CNA and tumor grade. Regarding deleted genes, CHMP7 (chr8p21.3) possessed the largest correlation between CNA and gene expression. Protein products of both genes interact with other cellular proteins to carry out various functional roles. These include ASH1L, ZNF496, YY1, ZMYM4, CHMP4A, CHMP5, CHMP2A and CHMP3, some of which are well-known cancer-related genes.ConclusionsOur in-silico analysis demonstrates the importance of copy number alterations in the pathology of HCC. These findings open a door for future studies that evaluate our results by performing additional experiments.
Highlights
Hepatocellular carcinoma (HCC) is the most common type of liver cancer that occurs predominantly in patients with previous liver conditions
By means of an in silico analysis, we have evaluated the patterns of copy number alteration (CNA) in liver HCC samples to identify hotspot chromosomal regions that are altered during the course of disease
Chromosomal cytobands chr1q and chr8q were strongly associated with gene amplification in HCC samples Of 24,776 examined genes, 1024 (4.1%) were amplified in HCC samples
Summary
Hepatocellular carcinoma (HCC) is the most common type of liver cancer that occurs predominantly in patients with previous liver conditions. Recent studies show that loss or gain of genomic materials can activate the oncogenes or inactivate the tumor suppressor genes to predispose cells toward carcinogenesis. We evaluated both the copy number alteration (CNA) and RNA sequencing data of 361 HCC samples in order to locate the frequently altered chromosomal regions and identify the affected genes. No effective screening modality exists for HCC This necessitates identifying the key genetic factors and new potential therapeutic targets. This is a complicated process because of the heterogeneous nature of HCC [4]
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