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

Department of Gastroenterology, 117nd Hospital of People's Liberation Army, Hangzhou, China.
Zhonghua zhong liu za zhi [Chinese journal of oncology] 01/2012; 34(1):21-5. DOI: 10.3760/cma.j.issn.0253-3766.2012.01.005
Source: PubMed


To investigate the relationship between p16 expression and cell proliferation and prognosis in gastric cancer patients.
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 mucosa from 65 patients were included in this study. RT-PCR, MTT and FCM assays were used to detect p16 expression in gastric cancer cell lines and surgical specimens of gastric cancer. MTT assay was used to determine cancer cell viability and FCM to detect cell cycle. Kaplan-Meier survival curve and Log-Rank statistics were used to analyze the relationship between p16 expression and survival of petients with gastric cancer.
Gastric cancer cell lines were mostly negative for p16 expression, and p16 was re-expressed after the cells transfected with p16 gene by adenovirus AdCMV-p16. p16 re-expression resulted in the decrease of cancer cell viability and cancer cell cycle arrest with increased G(1) 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 (χ(2) = 32.124, P < 0.001). The disease-free survival was significantly shorter in p16-negative patients than that in p16-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.
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.

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    ABSTRACT: Although gastric cancer (GC) is highly prevalent in China and is a leading cause of cancer-related death, major advances in early diagnostic and effective therapeutic strategies have not been made. Moreover, GC patients are usually diagnosed at an advanced stage and the prognosis is still poor. Over the years, many efforts have been done on exploring the pathology of GC. In particular, genome-wide analysis tools have been widely used in the detection of genetic and epigenetic alterations in GC. For example, many tumor suppressor genes have been found to be aberrantly hypermethylated in GCs, and some even in gastric precancerous lesions, suggesting a role of this molecular event in early gastric tumorigenesis. In addition, accumulating evidences have demonstrated that some hypermethylated genes can be used as potential biomarkers for detection and diagnosis of GC in biopsy specimens and non-invasive body fluids. These exciting advances provide unprecedented opportunities for the development of molecular-based novel diagnostic, prognostic, and therapeutic strategies for GC. Here, we reviewed recent findings on the promoter hypermethylation of tumor suppressor genes in GC and aimed to provide better understanding of the contribution of this epigenetic event to gastric tumorigenesis. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Jul 2015 · Clinica chimica acta; international journal of clinical chemistry