胃腺癌微环境caveolin-1的表达及其临床意义

Expression and Clinical Significance of Caveolin-1 in Microenvironment of Gastric Adenocarcinoma

背景:肿瘤的发生、发展是肿瘤微环境中肿瘤实质与间质成分共同作用的结果。目前仅少数研究探讨胃癌微环境小窝蛋白-1(caveolin-1)的表达情况、目的:探讨胃腺癌微环境caveolin-1的表达及其临床意义。方法:收集外科胃腺癌手术切除标本72例,32例正常胃窦黏膜组织作为对照,以免疫组化法检测实质和间质中的caveolin-1和原癌基因蛋白c-myc表达,分析胃癌实质caveolin-1表达与c-myc以及主要肿瘤临床病理特征的相关性。随机选取7例冰冻标本,激光捕获显微切割(LCM)技术获取纯净胃癌和癌旁组织实质和间质细胞,蛋白质印迹法检测caveolin-1和c-myc表达并行相关性分析。结果:常规标本中,胃癌实质和间质caveolin-1高表达率分别显著低于正常胃黏膜实质和间质(P<0.05):胃癌实质高表达c-myc,并与caveolin-1呈正相关(r=0.312,P<0.05)胃癌实质caveolin-1高表达与肿瘤浸润深度、淋巴结转移、TNM分期呈负相关(P<0.05)。LCM标本中,胃癌实质和间质caveolin-1表达分别显著低于相应癌旁组织实质和间质(P<0.05)。caveolin-1与c-myc在胃癌实质中的表达呈正相关(r=0.752,P<0.05),在胃癌间质中的表达呈负相关(r=-0.975,P<0.05)。结论:胃腺癌微环境低表达caveolin-1。胃癌实质caveolin-1高表达与肿瘤浸润、转移、临床进展呈负相关。c-myc可能通过不同机制调节胃癌实质和间质中的caveolin-1表达。胃癌间质caveolin-1低表达有望为胃癌预后判断提供依据。

Background：Tumorigenesis and progress is the result of combined action of parenchyma and stroma in tumor microenvironment.The expression of caveolin-1 in microenvironment of gastric cancer has been seldomly investigated. Aims：To investigate the expression and clinical significance of caveolin-1 in microenvironment of gastric adenocarcinoma （GAC）.Methods：Seventy-two surgical resected specimens of GAC and thirty-two normal antral specimens as controls were obtained for immunohistochemical assessment of the expressions of caveolin-1 and proto-oncogene protein cmyc in parenchyma and stroma.The correlation between parenchymal caveolin-1 and c-myc,as well as between parenchymal caveolin-1 and main clinicopathological characteristics of GAC was analyzed.Seven frozen specimens of GAC were subjected to laser capture microdissection（LCM） at random to obtain the pure parenchymal and stromal cells of cancerous and paracancerous tissues.Western blot was conducted to determine the expressions of caveolin-1 and c-myc, and the correlation between these two proteins was analyzed.Results：In routine specimens,the high expression rate of caveolin-1 in parenchyma and stroma of GAC was lower than that of normal gastric mucosa,respectively（P0.05）.The expression of c-myc was upregulated in parenchyma of GAC,and was positively correlated with caveolin-1（r=0.312,P0.05）.The high expression of caveolin-1 in parenchyma was negatively correlated with the depth of invasion,lymph node metastasis and TNM stage of GAC（P0.05）.Samples obtained by LCM showed that the expression of caveolin-1 in parenchyma and stroma of GAC was lower than that of paracancerous tissues,respectively（P0.05）.The expression of caveolin-1 was positively correlated with c-myc in parenchyma（r=0.752,P0.05）,and was negatively correlated with cmyc in stroma（r=-0.975,P0.05）.Conclusions：The expression of caveolin-1 in microenvironment of GAC is downregulated.The high expression of caveolin-1 in parenchyma is negatively correlated with invasion,metastasis and clinical progress of GAC.c-myc may regulate the expression of caveolin-1 in parenchyma and stroma of GAC by different mechanisms,and lower expression of caveolin-1 in stroma may provide a basis for prognostic prediction of GAC.