Expression of multiple tumor suppressor gene p16 and its relationship with prognosis of gastric cancer patients

Objective To investigate the relationship between p16 expression and cell proliferation and prognosis in gastric cancer patients. Methods Gastric cancer cell lines SGC-7901, MKN45, MKN28, human embryonic kidney cell line HEK293, human fibroblast cell line MRC-5, and surgical specimens of gastric carcinoma and adjacent normal gastric mucasa from 65 patients were included in this study. RT-PCR, MTI＂ and FCM assays were used to detect p16 expression in gastric cancer cell lines and surgical specimens of gastric cancer. MTr assay was used to determine cancer cell viability and FCM to detect cell cycle. Kaplan-Meicr survival curve and Log-Rank statistics were used to analyze the relationship between p16 expression and survival of potients with gastric cancer. Results Gastric cancer cell lines were mostly negative for p16 expression, and p16 was re-expressed after the cells transfected with p16 gene by adenovims AdCMV-pl6. p16 re-expression resulted in the decrease of cancer cell viability and cancer cell cycle arrest with increased Gl phase and decreased S phase, p16 expression in cancer specimens was 32.3% （21/65）, significantly lower than the 81.5% （ 53/65 ） in normal mucosa （X2 = 32.124, P 〈 0. 001 ）. The disease-rice survival was significantly shorter in pl6-negative patients than that in pl6-positive patients （P 〈 0.01 ）, but not the overall survival （ P 〉 0.05 ）. p16 expression was significantly correlated with differentiation and lymph node metastasis, but not significantly correlated with sex, age, tumor size or invasion depth of the gastric cancer. Conclusions p16 gene is important for cancer cell proliferation. The inactivation gives cancer cells a high activity for proliferation and metastasis, and then influences the disease-free survival of gastric cancer patients. Key words: Stomach neoplasms;  Gene, p16;  Cell proliferation;  Cell cycle;  Prognosis