Clinicopathologic and prognostic values of apolipoprotein D alterations in hepatocellular carcinoma.
We previously identified apolipoprotein D (Apo D) as a novel tumor suppressor gene based on the pharmacological unmasking of epigenetic silencing. We analyzed Apo D expression using real-time reverse transcription-PCR and evaluated its expression status based on the clinicopathological parameters of 70 patients with hepatocellular carcinoma (HCC). Immunohistochemical staining was also performed. We determined the methylation status of Apo D gene promoter by methylation-specific PCR (MSP). The Apo D gene-expression in tumor tissue was significantly lower than that in nontumor tissue (p = 0.011). A low Apo D expression significantly correlated with less-differentiated HCC (p = 0.019). Immunohistochemical studies confirmed a decreased Apo D expression in poorly differentiated tumors. The prognosis of patients with a lower Apo D gene-expression was significantly worse than that in those with a higher expression (p = 0.028). The Apo D gene-expression was an independent prognostic factor (relative risk: 2.36, p = 0.018). An MSP assay showed a low-level of methylation in well differentiated HCC and a high-level of methylation in less differentiated tumors. Apo D may be a novel tumor suppressor gene of HCC, and its expression status may be a useful biomarker for predicting the patient outcome.
Utsunomiya
Tohru
T
Department of Surgery, Medical Institute of Bioregulation, Kyushu University, Beppu, Japan.
Ogawa
Kazuhiko
K
Yoshinaga
Keiji
K
Ohta
Mitsuhiko
M
Yamashita
Keishi
K
Mimori
Koshi
K
Inoue
Hiroshi
H
Ezaki
Takahiro
T
Yoshikawa
Yasuji
Y
Mori
Masaki
M
D000368:Aged; D001053:Apolipoproteins / Q000235:genetics*; D053399:Apolipoproteins D; D001374:Azacitidine / Q000494:pharmacology; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D019175:DNA Methylation; D005260:Female; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D014407:Tumor Cells, Cultured
D001053:Apolipoproteins; D053399:Apolipoproteins D; D012333:RNA, Messenger; D001374:Azacitidine