肿瘤干细胞标志物LGR5及ALDH1在卵巢癌组织中的表达及临床意义

摘要

目的 探讨肿瘤干细胞标志物含亮氨酸重复序列G-蛋白偶联受体5(1eucine-rich repeat-containing G protein coupled receptor 5,Lgr5)及乙醛脱氢酶1(aldehyde dehydro-genase 1,ALDH1)在卵巢癌中的表达与临床意义.方法 选取2006年5月至2010年1月住院并接受手术治疗的卵巢癌患者140例,选取同期本院因卵巢良性病变行肿物剥除或附件切除的40例患者作为对照,应用免疫组化(S-P)方法检测140例卵巢癌组织(卵巢癌组)、140例卵巢癌癌旁组织(癌旁组)、正常卵巢组织40例(正常组)中的Lgr5及ALDH1蛋白表达,分析其与卵巢癌患者临床病理指标的关系.结果 (1)Lgr5在正常卵巢组织、癌旁组织和卵巢癌中的阳性率(5.0% vs 18.3% vs 95.7%)差异具有统计学意义(P=0.001);ALDH1在正常卵巢组织、癌旁组织和卵巢癌中的阳性率(7.5% vs 15.7% vs 90.0%)差异具有统计学意义(P<0.05).(2)Lgr5表达与肿瘤分化程度、淋巴结转移及TNM分期有关(P<0.05).ALDH1表达与肿瘤分化程度、浸润深度、淋巴结转移及TNM分期有关(P<0.05).(3)Lgr5及ALDH1存在正相关性(r=0.3,P<0.05).(4)Lgr5高表达者(+++)和低表达者(+)~(++)5年总生存率分别为51.2%和29.2%(HR=11.637,95%CI:4.351~38.213;P=0.002);ALDH1高表达者(+++)和低表达者(+)~(++)5年总生存率分别为41.3%和35.3%(HR=10.143,95%CI:4.285~33.275;P=0.006)..多因素Cox回归分析显示,Lgr5蛋白(+++)表达(P=0.002)、ALDH1蛋白(+++)表达(P=0.006)、分化程度(P=0.036)、浸润深度(P=0.001)和远处转移(P=0.002)是影响胃癌患者预后的独立因素.结论 Lgr5及ALDH1的增强表达与卵巢癌侵袭性增强有密切关系,其表达可作为判断卵巢癌患者预后的指标.%Objective To study LGR5 and ALDH1 expression in cervical carcinoma,and analyze its clinical significance.Methods Immunohistochemistry staining method was performed in 140 patients with cervical carcinoma and 40 patients with benign cervical tumor from May 2006 to January 2010 in our hospital.LGR5 and ALDH1 in the cervical carcinoma tissues (cervical carcinoma group,140 cases),para-carcinoma tissues(para-carcinoma group,140 cases) and normal cervical tissues (normal group,40 cases) were detected with immunohistochemica1 method.We also analyzed the its correlation with clinic pathological parameters of cervical carcinoma.Results (1)There was a significant difference of positive expression rate of Lgr5 among control group, surrounding tissue and cervical carcinoma(5.0% vs 18.3% vs 95.7%)(P<0.05).There was a significant difference of positive expression rate of ALDH1 among control group, surrounding tissue and cervical carcinoma(7.5% vs 15.7% vs 90.0%)(P=0.001).(2)The expression of Lgr5 was correlated with stage,the degree of tumor differentiation, lymph node metastasis and TNM (P<0.05).The expression of ALDH1 was correlated with stage and the degree of tumor differentiation, depth of invasion, lymph node metastasis and TNM (P<0.05).There is a positive correlation between LGR5 and ALDH1 expression(r=0.3,P<0.05).The Five-year overall survival(OS)rates for patients with high LGR5 expression(+++) and low expression(+)-(++) were 51.2% and 29.2%(HR:11.637,95%CI:4.351-38.213,P=0.002).The five-year overall survival(OS)rates for patients with high ALDH1 expression(+++) and low expression(+)-(++) were 41.3%and 35.3%(HR:10.143,95%CI:4.285-33.275,P=0.006).Multivariate Cox regression analysis showed that Lgr5(+++)(P=0.002),ALDH1(+++)(P=0.006),histology differentiation(P=0.036),tumor invasion(P=0.001),and distant metastasis(P=0.002) were independent prognostic factors.Conclusion The up-regulated expression level of LGR5 and ALDH1 was closely related to the increased malignancy and invasion of tumors.The expression of protein might act as an indicator the prognosis of patients with astrocyte tumors.