Beclin1表达在胃癌发生和演进中的临床病理意义及作用机制

Clinicopathological Significance and Relevant Molecular Mechanisms of Beclin 1 in Gastric Cancer

目的阐明胃癌发生和演进过程中Beclin 1表达的临床病理意义和分子作用机制。方法胃癌细胞MKN28转染Beclin 1表达质粒,利用CCK-8试剂盒和碘化丙啶染色检测细胞增殖和周期。利用原位杂交和免疫组化检测组织芯片上胃癌、癌旁黏膜和淋巴结转移灶中Beclin 1 m RNA和蛋白的表达,比较其与胃癌发生、临床病理特征和预后的关系。结果 Beclin 1过表达可以抑制胃癌细胞MKN28增殖并导致细胞周期G2期阻滞,胃癌中Beclin 1 m RNA表达高于癌旁黏膜(P<0.05),Beclin 1蛋白表达与胃癌远处转移呈负相关(P<0.05),Beclin 1表达病例多见于老年男性(P<0.05),弥漫型胃癌中Beclin 1表达低于肠型和混合型(P<0.05)。Kaplan-Meier分析显示,Beclin 1表达与胃癌良好预后呈正相关(P<0.05)。结论 Beclin 1表达与胃癌发生、转移和分化关系密切,可以作为胃癌患者的预后因素和基因治疗的靶标。

Objective To explore the role of Beclin 1 in gastric carcinogenesis and subsequent progression. Methods MKN28 cells were trans- fected with Beclin 1-expressing plasmid, and then the proliferation and cell cycle was measured by CCK-8 and PI staining. Beclin 1 expression was examined by immunohistochemistry and in situ hybridization on tissue microarrays containing gastric cancers, adjacent non-neoplastic mucosa, and metastatic lymph node. The correlation with the tumorgenesis, clinicopathological and prognostic parameters was analyzed. Results Beclin I overex- pression resulted in G2 arrest of MKN28 cells and reduced the proliferation. Beclin 1 mRNA was highly expressed in gastric cancer than matched mu- cosa by ISH （P 〈 0.05）. Beclin 1 was highly expressed in male than female patients with gastric cancer （P 〈 0.05）. The elder patients with gastric cancer had higher Beclin 1 expression than younger ones （P 〈 0.05 ）. The diffuse-type carcinomas showed less Beclin 1 expression than intestinal and mixed type ones （P 〈 0.05 ）. Kaplan-Meier analysis indicated that Beclin 1 expression was positively correlated to favorable prognosis of the can- cer patients （P 〈 0.05 ）. Conclusion Beclin 1 expression is closely linked to pathogenesis, metastasis and differentiation of gastric cancer. Beclin 1 might be employed to indicate the favorable prognosis of gastric cancer patients and regarded as a target of gene therapy.