Overexpression of pituitary tumor transforming gene 1 in HCC is associated with angiogenesis and poor prognosis.
The pituitary tumor transforming gene 1 (PTTG1) protein is cell-cycle regulated and is identified as a human securin that inhibits sister chromatid separation and is involved in transformation and tumorigenesis. PTTG1 has very low or undetectable expression in most normal human tissues, but it is abundantly expressed in malignant cell lines and pituitary tumors. In this study, we investigated human PTTG1 expression in 62 hepatocellular carcinoma (HCC) specimens using quantitative real-time reverse transcription polymerase chain reaction analysis. We found that, compared with corresponding noncancerous liver tissues, PTTG1 was remarkably overexpressed in HCCs (PTTG1/beta-actin; 0.443 +/- 0.073 vs. 0.068 +/- 0.007; P < .0001). Furthermore, we found a significant correlation between PTTG1 expression and serum alpha-fetoprotein level (P < .001). Univariate and multivariate analyses revealed that the PTTG1 messenger RNA (mRNA) expression was an independent prognostic factor for disease-free (odds ratio 2.70; P = .037) and overall (odds ratio 5.35; P = .007) survival. Moreover, we discovered a significant relationship between PTTG1 expression and intratumoral microvessel density. Our data supported an important role for PTTG1-mediated upregulation of fibroblast growth factor (FGF)-2, one of angiogenesis and modulation of tumor progression, in hepatocarcinogenesis. In conclusion, PTTG1 might be critically involved in the development of HCCs through the promotion of angiogenesis. PTTG1 is overexpressed in HCC and our results suggest that PTTG1 mRNA expression has prognostic significance for the survival of postoperative patients with HCC.
Fujii
Tsutomu
T
Department of Surgery II, Graduate School and Faculty of Medicine, Nagoya University, Nagoya, Japan.
Nomoto
Shuji
S
Koshikawa
Katsumi
K
Yatabe
Yasushi
Y
Teshigawara
Osamu
O
Mori
Toshiaki
T
Inoue
Soichiro
S
Takeda
Shin
S
Nakao
Akimasa
A
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009367:Neoplasm Staging; D009389:Neovascularization, Pathologic / Q000235:genetics*; D011336:Probability; D011379:Prognosis; D016016:Proportional Hazards Models; D012334:RNA, Neoplasm / Q000032:analysis; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012494:Sampling Studies; D064249:Securin; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D015996:Survival Rate; D046509:Tissue Culture Techniques
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D064249:Securin; C578002:pituitary tumor-transforming protein 1, human