Prognostic relevance of Tensin4 expression in human gastric cancer.
BACKGROUND
The Tensin4 gene is involved in various biological events by mediating signal transduction. This study was designed to clarify its clinical significance in gastric cancer.


METHODS
A total of 114 gastric cancer patients were enrolled in this study, and we obtained paired samples from tumor tissue and matched normal mucosa. Total RNA was extracted, and TNS4 mRNA expression was quantified using real-time reverse-transcription polymerase chain reaction. TNS4 protein expression was investigated by immunohistochemistry. Additionally, the relationship between TNS4 expression and clinicopathologic factors was statistically analyzed.


RESULTS
TNS4 mRNA expression was significantly higher in tumor tissue than in normal mucosa (p < 0.0001). Additional immunohistochemical analysis demonstrated that TNS4 protein was predominantly expressed in gastric cancer. Tumors with higher TNS4 mRNA expression showed histologically poorer grade (p < 0.02), deeper invasion into the serosa (p < 0.01), more positive lymph node metastasis (p < 0.02) or peritoneal dissemination (p < 0.05). Patients with high TNS4 mRNA expression tumor were more likely to have cancer-related death (p < 0.05). A Kaplan-Meier curve also demonstrated that patients with high TNS4 expression tumor had significantly poorer prognosis (p < 0.01) than those with low TNS4 expression tumor. In particular, the 2-year overall survival rates were 48.2% and 83.1%, respectively, a very significant difference. Multivariate analysis revealed that high TNS4 mRNA expression was an independent prognostic predictor (relative risk 1.41, 95% confidence interval 1.03-1.96, p = 0.03).


CONCLUSIONS
TNS4 was frequently overexpressed in gastric cancer, and tumors with high TNS4 mRNA expression showed biologically aggressive behavior. High TNS4 mRNA expression may be a novel prognostic predictor for those patients.
Sakashita
Katsuya
K
Department of Surgical Oncology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, 874-0838, Japan.
Mimori
Koshi
K
Tanaka
Fumiaki
F
Kamohara
Yukio
Y
Inoue
Hiroshi
H
Sawada
Tetsuji
T
Hirakawa
Kosei
K
Mori
Masaki
M
D000230:Adenocarcinoma / Q000235:genetics* / Q000556:secondary; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism; D009367:Neoplasm Staging; D010534:Peritoneal Neoplasms / Q000235:genetics* / Q000556:secondary; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D015996:Survival Rate; D000070876:Tensins; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D008840:Microfilament Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C000603371:TNS4 protein, human; D000070876:Tensins