JAG1和Notch3在乳腺癌组织中的表达及预后价值

目的探讨JAG1和Notch3在乳腺癌组织中的表达水平及预后意义。方法通过在线Oncomine数据库和Kaplan-Meier Plotter数据库分析JAG1和Notch3在乳腺癌组织中的表达情况及对预后的影响。收集2008年1月至2013年12月乳腺浸润性导管癌组织及配对癌旁组织各80例,采用实时荧光定量PCR(QPCR)和免疫组织化学SP法分别检测JAG1和Notch3的mRNA和蛋白水平,分析JAG1和Notch3蛋白表达与乳腺癌临床病理特征和总生存时间(OS)的关系。多因素分析采用Cox比例风险回归模型。结果 Oncomine数据库分析显示,乳腺癌组织中JAG1和Notch3的mRNA水平均高于癌旁组织(P<0.05)。80例乳腺浸润性导管癌组织中JAG1 mRNA水平为1.58±0.56,高于癌旁组织的1.23±0.48(P=0.0039);乳腺浸润性导管癌组织中Notch3 mRNA水平为2.39±0.83,高于癌旁组织的1.95±0.64(P=0.0036)。JAG1和Notch3蛋白在乳腺癌组织中的高表达率为71.3%(57/80)和80.0%(64/80),分别高于癌旁组织的8.8%(7/80)和11.2%(9/80),差异均有统计学意义(P=0.005,P=0.003). JAG1和Notch3蛋白表达在乳腺癌组织中呈正相关(r=0.267,P=0.017)。JAG1和Notch3表达与乳腺癌淋巴结转移、TNM分期和组织学分级有关(P<0.05)。Kaplan-Meier Plotter在线分析显示, JAG1或Notch3高表达的乳腺癌患者的OS短于低表达者(P>0.05)。80例乳腺浸润性导管癌患者中,JAG1高表达者的中位OS为38.3个月,低于JAG1低表达者的80.4个月(P=0.0394);Notch3高表达者的中位OS为39.3个月,低于Notch3低表达者的80.2个月(P=0.0334),且JAG1和Notch3均高表达者的中位OS最短,为27.3个月。Cox多因素分析显示,淋巴结转移、JAG1表达和Notch3表达是影响乳腺癌患者OS的独立因素(P<0.05)。结论 JAG1和Notch3在乳腺癌组织中高表达,且与预后不良有关,有望成为临床评估乳腺癌预后的潜在生物标志物。

Expression of JAG1 and Notch3 in breast cancer tissues and their prognostic value

Objective To explore the expression levels of JAG1 and Notch3 in breast cancer tissues and their prognostic significance.Methods The expression of JAG1 and Notch3 in breast cancer was analyzed by online Oncomine database and their prognostic value was explored by Kaplan-Meier Plotter database.From January 2008 to December 2013,80 pairs of infiltrating ductal cancer tissues and adjacent tissues were collected.Immunohistochemistry and QPCR were used to detect the protein and mRNA expression levels of JAG1 and Notch3 in the above tissues,and the relationship between clinical pathological parameters and overall survival(OS)of breast cancer patients was analyzed.Multivariate analysis was performed by Cox proportional hazard model.Results Oncomine database analysis showed that JAG1 and Notch3 mRNA levels in breast cancer tissues were significantly higher than those in adjacent tissues(P<0.05).JAG1 mRNA level of 80 cases of breast cancer tissues was 1.58±0.56,higher than 1.23±0.48 in adjacent tissues(P=0.0039).Meanwhile,Notch3 mRNA level in 80 breast cancer tissues was 2.39±0.83,higher than 1.95±0.64 in adjacent tissues(P=0.0036).The high expression rates of JAG1 and Notch3 protein in breast cancer tissues were 71.3%(57/80)and 80.0%(64/80),higher than 8.8%(7/80)and 11.2%(9/80)of adjacent tissues with statistical differences(P=0.005,P=0.003).The expression of JAG1 and Notch3 was positively correlated in breast cancer tissues(r=0.267,P=0.017).The expressions of JAG1 and Notch3 were significantly correlated with lymph node metastasis,TNM staging and tumor differentiation in breast cancer tissues(P<0.05).Kaplan-Meier Plotter online analysis showed that breast cancer patients with high expression of JAG1 or Notch3 had shorter OS than those with low expression(P>0.05).The median OS in patients with JAG1 high expression was 38.3 months,less than 80.4 months in those with JAG1 lower expression(P=0.0394).The median OS in patients with Notch3 high expression was 39.3 months,less than 80.2 months in patients with Notch3 low levels(P=0.0334).Moreover,the median OS(27.3 months)of patients with both high expression of JAG1 and Notch3 was the worst.Lymph node metastasis,JAG1 and Notch3 were independent factors influencing OS of breast cancer patients.Conclusion JAG1 and Notch3 are high expressed in breast cancer tissues,and related to poor prognosis.They are expected to be potential biomarkers for prognostic evaluation in breast cancer.