CLDN18表达在胃癌进展中的意义

Significance of CLDN18 Expression in Gastric Cancer Progression

目的:探讨CLDN18表达与胃癌临床病理特征之间的关系。方法:组织芯片免疫组化染色法检测胃癌claudin-18蛋白表达,Real-time PCR法检测胃癌CLDN18 mRNA的表达。结果:胃癌组织claudin-18表达显著降低,并与组织学类型和浸润相关,肠型胃癌和浸润在肌层以内者其黏膜层claudin-18的下调表达率明显高于弥漫型胃癌或浸润程度超过肌层者。从黏膜层进展至侵袭前缘区,claudin-18的下调表达率逐渐升高,黏膜层claudin-18表达水平明显高于侵袭前沿区。进展期胃癌黏膜层癌组织claudin-18表达未下调者34例进展至侵袭前沿区28例转变为表达下调,其中弥漫型胃癌、浸润程度超过肌层者、有淋巴结转移者以及非贲门胃癌者发生率均高于肠型胃癌、浸润程度在肌层内者、无淋巴结转移者以及贲门胃癌者。52例胃癌黏膜层胃癌组织CLDN18 mRNA表达下调者20例,其相对表达量与浸润程度及肿瘤大小有关。结论:胃癌的进展中claudin-18表达降低,组织学类型的维持与其密切相关。

Objective： To study relationship between CLDN18 gene expression and the clinicopathologic features of gastric cancer （ GC ）. Methods： A tissue microarray was made and immunohistochemistry was performed to detect the expression of elaudin-18 protein. Real-time polymerase chain reaction was conducted to examine mRNA expression of CLDN18 gene. Results： Expression of claudin-18 protein in GC was significantly downregulated and was correlated with histologic types and extent of invasion, which was greatly decreased in the intestinal-type and intramuscular infiltration of GC than in the diffuse-type and the extramuscular extension, respectively. There was a gradual downregulation of claudin-18 expression from the mucosa to the front of the invasion. Claudin-18 expression was higher in the mucosa than at the front of invasion. Of the 34 cases with advanced GC without downregulation of claudin-18 expression in mucosa, 28 had claudin-18 downregulation as GC developed to the front of the invasion. In the 28 cases, the incidences of the diffuse-type GC, extramuscular infiltration, lymph node metastasis, and non-cardiac GC were higher compared with the intestinal-type, intramuscular, non-metastatic, and cardiac GC. CLDN18 mRNA expression was downregulated in 20 of the 52 GC cases. The relative expression was associated with the infiltration and size of the tumors. Conclusion： Downregulation of claudin-18 expression is involved in the progression of disease, and in maintaining the phenotype of gastric adenocarcinoma.