Sex-based molecular profiling of hepatitis C virus-related hepatocellular carcinoma.
It has been suggested that sex affects not only the incidence of hepatocellular carcinoma (HCC) but also the outcome after treatment. However, no sex-specific therapeutic targets for HCC have been identified. Identification of sex-specific genes will allow for the development of more personalized therapies. To this end, we investigated the expression of approximately 6000 genes in 50 samples of hepatitis C virus (HCV)-related HCC by oligonucleotide microarray. Our supervised learning method and subsequent random permutation test identified 27 genes that were differentially expressed in samples from male (n=34) and female (n=16) patients. Our gene selection was validated by a false discovery rate of only 0.5%. For the 27 genes, expression levels of 12 were higher and expression levels of 15 were lower in HCC samples from men than in HCC samples from women. For the cell proliferation-related genes identified, expression levels of PRDX1 were relatively high in HCC samples from men, and expression levels of PRDX3 were relatively high in HCC samples from women. The DNA microarray data for PRDX1 and PRDX3 were reproduced by reverse transcription-PCR analysis. Our results suggest that these 27 genes may serve as molecular targets or markers for sex-specific treatment of HCV-related HCC. Further studies are needed to elucidate their possible roles in male and female patients with HCV-related HCC.
Takemoto
Norikazu
N
Department of Surgery II, Yamaguchi University School of Medicine, Ube, Yamaguchi 755-8505, Japan.
Iizuka
Norio
N
Yamada-Okabe
Hisafumi
H
Hamada
Kenji
K
Tamesa
Takao
T
Okada
Toshimasa
T
Hashimoto
Kiichiro
K
Sakamoto
Kazuhiko
K
Takashima
Motonari
M
Miyamoto
Takanobu
T
Uchimura
Shunji
S
Hamamoto
Yoshihiko
Y
Oka
Masaaki
M
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006360:Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010347:Patient Care Planning; D010544:Peroxidases / Q000096:biosynthesis / Q000235:genetics* / Q000494:pharmacology; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D011505:Protein-Tyrosine Kinases; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors
D005819:Genetic Markers; D006360:Heat-Shock Proteins; D009363:Neoplasm Proteins; D010544:Peroxidases; C515940:PRDX1 protein, human; C516115:PRDX3 protein, human; D061105:Peroxiredoxin III; D054464:Peroxiredoxins; D011505:Protein-Tyrosine Kinases