Gene expression profiling of human HBV- and/or HCV-associated hepatocellular carcinoma cells using expressed sequence tags

Abstract

Abstract. Liver cancer is one of the leading causes of cancer death worldwide. To identify novel target genes that are related to liver carcinogenesis, we examined new genes that are differentially expressed in human hepatocellular carcinoma (HCC) cell lines and tissues based on the expressed sequence tag (EST) frequency. Eleven libraries were constructed from seven HCC cell lines and three normal liver tissue samples obtained from Korean patients. An analysis of gene expression profiles for HCC was performed using the frequency of ESTs obtained from these cDNA libraries. Genes were identified (n=120) as being either up-or downregulated in human liver cancer cells. Among these, 14 genes (FTL, LDHA, RPL4, ENO1, ANXA2, RPL9, RPL10, RPL13A, GNB2L1, AMBP, GC, A1BG, and SERPINC1), in addition to previously well-known liver cancer related genes, were confirmed to be differentially expressed in seven liver cancer cell lines and 17 HCC tissues by semi-quantitative RT-PCR. In addition, 73 genes, in which there was a significant difference (P>0.99) between HBV-and HCV-associated HCC cells, were selected. Of these, expression patterns of 14 (RPLP0, AKR1C, KRT8, GPX4, RPS15, ID1, RPS21, VIM, EEF1G, EIF4A1, FN1, CD44, and RPS10) were confirmed by semiquantitative RT-PCR in four of HBV-and three of HCVassociated HCC cell lines. Among those genes, an immunohistochemical analysis for ANXA2 showed that it is expressed at high levels in HCC. Using an analysis of EST frequency, the newly identified genes, especially ANXA2, represent potential biomarkers for HCC and useful targets for elucidating the molecular mechanisms associated with HCC involving virological etiology.

Bladder Cancer Associated Glycoprotein Signatures Revealed by Urinary Proteomic Profiling

“…In a study that utilized expressed sequence tag (EST) profiling of cDNA libraries, Yoon et al identified A1BG as 1 of 14 genes confirmed to be highly expressed in human hepatocellular carcinoma (HCC) cell lines and liver tumor tissue specimens. 35 While many more cases are required to be screened, the reported correlation of A1BG expression with liver cancer supports the notion that this protein is worthy of further study in the context of a potential biomarker for bladder cancer. Haptoglobin was also associated with bladder cancer in this study, and this glycoprotein has been reported to be diagnostically useful in both ovarian and liver cancer.…”

“…Haptoglobin was also associated with bladder cancer in this study, and this glycoprotein has been reported to be diagnostically useful in both ovarian and liver cancer. 34,35 Further studies are needed in large cohorts of bladder cancer patients with a broad range of disease stage and grade and with noncancer conditions to evaluate the true potential of the glycoproteins implicated in this study in bladder disease management. Beyond the investigation of individual proteins identified here, the described technical approach will facilitate a more focused analysis of clinically relevant samples, such as urine and other bodily fluids, which in turn will lead to the identification of reliable biomarkers for improved detection, surveillance, and screening regimens for a range of diseases.…”

Comparative Proteomic Expression Profile in All-trans Retinoic Acid Differentiated Neuroblastoma Cell Line

“…62 Furthermore, the DDX1, eIF4A1, eIF4A2, eEF1-gamma, and LDH genes are detected in several NB cDNA libraries. Moreover, eIF4A1 mRNA has been shown to be consistently overexpressed in human melanoma cells in vitro, 63 in hepatocellular carcinoma 64,65 and in early stage non-smallcell lung cancer. 66 The SH-SY5Y and SK-N-BE human NB cell lines are able to undergo neuronal differentiation in the presence of ATRA.…”

Transcriptome analysis of hepatitis B virus-associated small hepatocellular carcinoma by serial analysis of gene expression

“…Large scale sequencing of expressed sequence tags (ESTs) can detect novel transcripts, and numerical comparisons of ESTs are, in theory, possible between two unrelated cDNA libraries. Because generation of comprehensive library needs a huge number of sequencing, however, there have been only a few studies of large scale EST libraries from HCC tissues (13)(14)(15). As each library was generated from only a few patients, heterogeneity of gene expression profiles makes it difficult to interpret the variable results from these studies.…”