Exploration of potential genomic portraits associated with intrahepatic recurrence in human hepatocellular carcinoma.
BACKGROUND
Hepatocellular carcinoma (HCC) is a heterogeneous disease with recognized variability in virus infection, genetic features, and clinical outcome. To date, transcriptional profilings of HCC have been used to predict recurrence or survival/prognosis. However, there remains a challenge to identify specific genomic prints associated with HCC recurrence, which could lead to novel therapies or effective treatment. Here we examine the association between biological signals and intrahepatic recurrence using global gene expression profiles and powerful analytical methods.


METHODS
Gene expression profiles were generated in 24 HCC patients with hepatitis B infections (B-type HCC) and 60 HCC patients with hepatitis C infections (C-type HCC). Gene set enrichment analysis (GSEA) was applied to the entire ranked gene lists related to early intrahepatic recurrence, based on "ideal discriminator method."


RESULTS
GSEA revealed Ribosomal Proteins as a common regulatory pathway in B-type (P < .001) and C-type (P = .003) HCC recurrence. In addition, Proteasome (P < .001) and Pentose Phosphate Pathway (P = .01) were identified as specific pathways in each type of HCC recurrence, respectively.


CONCLUSIONS
Understanding these biologically common and different mechanisms related to intrahepatic recurrence in B-type and C-type HCC could be useful in the development of new therapeutic strategies in our fight against HCC.
Kittaka
Nobuyoshi
N
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Osaka, Japan.
Takemasa
Ichiro
I
Seno
Shigeto
S
Takeda
Yutaka
Y
Kobayashi
Shogo
S
Marubashi
Shigeru
S
Dono
Keizo
K
Umeshita
Koji
K
Nagano
Hiroaki
H
Matsuda
Hideo
H
Monden
Morito
M
Mori
Masaki
M
Doki
Yuichiro
Y
D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000821:virology; D005260:Female; D020869:Gene Expression Profiling; D016174:Hepacivirus / Q000235:genetics; D006509:Hepatitis B / Q000235:genetics / Q000473:pathology / Q000821:virology; D006515:Hepatitis B virus / Q000235:genetics; D006526:Hepatitis C / Q000235:genetics / Q000473:pathology / Q000821:virology; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000473:pathology / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics
D014408:Biomarkers, Tumor; D012334:RNA, Neoplasm