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目的探讨雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)、p70S6激酶(p70S6kinase,p70S6K)及Lgr5蛋白在胃癌组织中的表达及相关性。方法采用免疫组织化学法检测132例胃癌患者手术切除的胃癌组织、癌旁组织标本和30例慢性非萎缩性胃炎患者胃镜下活检正常胃黏膜组织标本中mTOR、p70S6K和Lgr5蛋白表达,分析胃癌患者mTOR、p70S6K及Lgr5蛋白阳性表达率与临床病理特征的关系,对胃癌组织中Lgr5蛋白表达与mTOR、p70S6K蛋白表达的相关性进行分析。结果胃癌组织mTOR、p70S6K和Lgr5蛋白阳性表达率分别为65.15%、61.36%、70.45%,癌旁组织分别为24.24%、22.73%、34.09%,均高于正常胃黏膜组织(10.00%、13.33%、6.67%),且胃癌组织mTOR、p70S6K和Lgr5蛋白阳性表达率高于癌旁组织,差异均有统计学意义(P<0.05);不同性别,年龄≥50岁与<50岁胃癌患者mTOR、p70S6K和Lgr5蛋白阳性表达率比较差异均无统计学意义(P>0.05),肿瘤直径≥5cm胃癌患者mTOR、p70S6K和Lgr5蛋白阳性表达率(72.73%、74.03%、80.52%)高于肿瘤直径<5cm者(54.55%、43.64%、56.36%),TNM分期Ⅰ+Ⅱ期者(50.98%、45.10%、54.92%)低于Ⅲ+Ⅳ期者(74.07%、72.84%、80.52%),组织学分级G_1+G_2期者(53.70%,50.00%,55.56%)低于G_3+G_4期者(73.08%、69.23%,80.77%),淋巴结转移N_0者(42.22%、44.44%、46.67%)低于N_1+N_2+N_3者(77.01%、70.11%、82.76%),侵犯程度T_1+T_2期者(42.11%、42.11%、44.74%)低于T_3+T_4期者(74.47%、69.15%、80.85%),差异均有统计学意义(P<0.01);胃癌组织中Lgr5蛋白表达与mTOR、p70S6K蛋白表达呈正相关(r=0.579,P=0.004 6;r=0.502,P=0.007 1)。结论mTOR、p70S6K和Lgr5蛋白表达与胃癌肿瘤浸润程度、淋巴结转移、TNM分期、组织学分级密切相关,可作为评估胃癌患者预后的指标。
Objective To investigate the expression and correlation of mammalian target of rapamycin (mTOR), p70S6 kinase (p70S6K) and Lgr5 in gastric cancer. Methods The expressions of mTOR, p70S6K and Lgr5 protein in biopsied gastric mucosa specimens from 132 gastric cancer tissues, adjacent non-cancerous tissues and 30 patients with chronic non-atrophic gastritis were detected by immunohistochemical staining. mTOR, p70S6K and Lgr5 protein expression and clinicopathological features of gastric cancer, Lgr5 protein expression and mTOR, p70S6K protein expression analysis. Results The positive rates of mTOR, p70S6K and Lgr5 protein in gastric cancer tissues were 65.15%, 61.36% and 70.45%, respectively, which were 24.24%, 22.73% and 34.09%, respectively, which were higher than those in normal gastric mucosa tissues (10.00% and 13.33% , 6.67% respectively). The positive rates of mTOR, p70S6K and Lgr5 in gastric cancer tissues were higher than those in paracancer tissues (P <0.05) The positive rates of mTOR, p70S6K and Lgr5 protein in tumor with tumor diameter> = 5cm were higher than those with tumor diameter <5cm (72.73%, 74.03%, 80.52%), the positive rates of p70S6K and Lgr5 were not statistically significant (54.55%, 43.64%, 56.36%) were lower than those in patients with stage III + Ⅳ (74.07%, 72.84%, 80.52%) in TNM stage Ⅰ + Ⅱ (50.98%, 45.10%, 54.92% (53.70%, 50.00%, 55.56%) were lower than those in G_3 + G_4 stage (73.08%, 69.23%, 80.77%) and those with lymph node metastasis (42.22%, 44.44%, 46.67% (42.11%, 42.11%, 44.74%) were lower than those of T_3 + T_4 (74.47%, 69.15%, 80.85%) in the N_1 + N_2 + N_3 patients (77.01%, 70.11%, 82.76% ), The differences were statistically significant (P <0.01) ; The expression of Lgr5 protein in gastric cancer tissues was positively correlated with the expression of mTOR and p70S6K protein (r = 0.579, P = 0.004 6; r = 0.502, P = 0.007 1). Conclusion The expressions of mTOR, p70S6K and Lgr5 are closely related to the degree of tumor invasion, lymph node metastasis, TNM stage and histological grade in gastric cancer, which may be used as an index to evaluate the prognosis of patients with gastric cancer.