Self-organizing-map-based molecular signature representing the development of hepatocellular carcinoma.
Using high-density oligonucleotide array, we comprehensively analyzed expression levels of 12600 genes in 50 hepatocellular carcinoma (HCC) samples with positive hepatitis C virus (HCV) serology (well (G1), moderately (G2), and poorly (G3) differentiated tumors) and 11 non-tumorous livers (L1 and L0) with and without HCV infection. We searched for discriminatory genes of transition (L0 vs. L1, L1 vs. G1, G1 vs. G2, G2 vs. G3) with a supervised learning method, and then arranged the samples by self-organizing map (SOM) with the discriminatory gene sets. The SOM arranged the five clusters on a unique sigmoidal curve in the order L0, L1, G1, G2, and G3. The sample arrangement reproduced development-related features of HCC such as p53 abnormality. Strikingly, G2 tumors without venous invasion were located closer to the G1 cluster, and most G2 tumors with venous invasion were located closer to the G3 cluster (P=0.001 by Fisher's exact test). Our present profiling data will serve as a framework to understand the relation between the development and dedifferentiation of HCC.
Iizuka
Norio
N
Department of Surgery II, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan.
Oka
Masaaki
M
Yamada-Okabe
Hisafumi
H
Mori
Naohide
N
Tamesa
Takao
T
Okada
Toshimasa
T
Takemoto
Norikazu
N
Sakamoto
Kazuhiko
K
Hamada
Kenji
K
Ishitsuka
Hideo
H
Miyamoto
Takanobu
T
Uchimura
Shunji
S
Hamamoto
Yoshihiko
Y
D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000145:classification / Q000235:genetics* / Q000473:pathology*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D016174:Hepacivirus / Q000502:physiology; D006526:Hepatitis C / Q000150:complications / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53