Analysis of gene expression profiles as a tool to uncover tumor markers of liver cancer progression in a rat model

Abstract

Establishing a transcriptomic profile of human hepatocellular liver cancer (HCC) progression is a complex undertaking. A rat model of HCC was employed to develop a transcriptomic profile. Using three interventions, preneoplastic lesions appeared after 30 days and they progressed to HCC by 9 months. Preneoplastic and cancer lesions were characterized for transcriptomic analysis, and RNA from total liver homogenates was obtained at 1, 7, 11 and 16 days after the initiation treatment. RNA from dissected persistent preneoplastic lesions, adjacent tissue or cancer tissue was used for 30 days, and 5, 9, 12 and 18 months. The GeneChip Rat Exon 1.0 ST arrays, Partek software and an Affymetrix console were employed for these analyses. was differentially expressed at each time point, from the initial period, through the preneoplastic evolution period and until the end of cancer progression period. Twelve differentially expressed genes common to the preneoplastic evolution and to the cancer progression period were detected, which included. Validation of the microarrays was confirmed by reverse transcription-quantitative polymerase chain reaction of six genes, including and. Of note, the proteins of these two genes are associated with the multidrug response complex, and evasion of immune surveillance and negative regulation of T cell proliferation. This model is useful for identifying candidate genes, and to validate them with regards to determining their relevance in rat HCC progression.

Bioinformatics Analysis Reveals Distinct Molecular Characteristics of Hepatitis B-Related Hepatocellular Carcinomas from Very Early to Advanced Barcelona Clinic Liver Cancer Stages

“…Microarrays have been utilized to detect DEGs and non-coding RNA, such as microRNAs and long non-coding RNA in HCC, and especially in HBV-related HCC. Many DEGs have been identified as prognostic and diagnostic markers for the development of HCC [ 9 – 11 , 20 – 23 ]. In routine clinical practice, clinicians use staging systems to design different treatment programs, and the BCLC staging system is the most commonly used system for HCC management [ 4 ].…”

“…The differentially expressed genes (DEGs) and associated molecular abnormalities of HCC, especially HBV-related HCC, have been explored by many different groups [ 9 – 14 ]. However, to our knowledge, the reported studies mainly focused on the identification of distinct gene expression signatures and their usefulness as molecular markers in the prediction of clinical outcomes such as survival, metastasis, and recurrence in patients with HCC [ 12 – 14 ].…”

Downregulation of sorting nexin 10 is associated with overexpression of miR-30d during liver cancer progression in rats

“…As a follow-up study of possible candidate early cancer markers identified in our previous microarray study, 5 we selected a group of genes that were overexpressed in cancer and showed very small variations in the age-control group at 9 and 18 months. We performed a gene expression analysis of the following six selected genes: ANXA2, DYNLT1, PFKP, KRT19, PLA2G7, and SNX10.…”

“…These genes have been identified as candidates for further studies aiming to uncover cancer markers. 5 Of the identified candidate genes, ANXA2, DYNLT1, PFKP, PLA2G7, KRT19, and SNX10 genes were selected for this study. The validation of these six genes by quantitative real-time polymerase chain reaction (qRT-PCR) demonstrated high fold-changes in their expression in neoplastic lesions and low expression profiles in adjacent tissues.…”

Gene silencing of Nox4 by CpG island methylation during hepatocarcinogenesis in rats

“…Regarding the deregulation of genes via epigenetic mechanisms, we have previously described profound changes in gene expression during liver carcinogenesis using microarray-based gene expression profiling (GEP) ( Vasquez-Garzon et al, 2015 ), including the significant downregulation of several genes. Because deregulation of gene expression through methylation plays an important role in the carcinogenic process, it is necessary to identify new targets that participate in liver carcinogenesis.…”