Gene expression profiling of human HBV- and/or HCV-associated hepatocellular carcinoma cells using expressed sequence tags.
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 down-regulated in human liver cancer cells. Among these, 14 genes (FTL, K-ALPHA1, 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, HLA-C, FN1, CD44, and RPS10) were confirmed by semi-quantitative RT-PCR in four of HBV- and three of HCV-associated 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.
Yoon
Sun Young
SY
Laboratory of Human Genomics, Genome Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon 305-333, Korea.
Kim
Jeong-Min
JM
Oh
Jung-Hwa
JH
Jeon
Yeo-Jin
YJ
Lee
Dong-Seok
DS
Kim
Joo Heon
JH
Choi
Jong Young
JY
Ahn
Byung Min
BM
Kim
Sangsoo
S
Yoo
Hyang-Sook
HS
Kim
Yong Sung
YS
Kim
Nam-Soon
NS
D014408:Biomarkers, Tumor; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000821:virology*; D045744:Cell Line, Tumor; D018076:DNA, Complementary / Q000378:metabolism; D020224:Expressed Sequence Tags; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015723:Gene Library; D016174:Hepacivirus / Q000235:genetics*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000821:virology*; D020411:Oligonucleotide Array Sequence Analysis
D014408:Biomarkers, Tumor; D018076:DNA, Complementary