CBLC在各分型分期乳腺癌中的表达差异及预后分析

Expression differences and prognosis analysis of CBLC in breast cancer with different types and stages

目的阐明CBL原癌基因C(CBLC)在乳腺癌中的生物学作用,为乳腺癌的临床诊断与预后评估提供新的监测指标,为乳腺癌的深入研究和治疗方案拟定提供指导性理论基础。方法从USCS Xena(https://xenabrowser.net)中的TCGA数据集下载1104例乳腺癌组织和113例癌旁组织的基因表达谱矩阵,分析CBLC基因在乳腺癌各分子与病理分型、TNM分期与肿瘤阶段中的表达差异及预后相关性;利用免疫组化染色观察CBLC在30例乳腺癌患者肿瘤及其邻近正常组织中的表达水平;利用MCF7乳腺癌细胞进行划痕实验、Transwell实验及CCK-8实验,观察CBLC对其增殖迁移的作用。结果CBLC在乳腺癌组表达量(P=2.31×10^-20)及H-Score评分(P=0.014)均高于癌旁组,在Luminal A分子分型(P=1.68×10^-4)及黏液癌病理分型(P=4.00×10^-5)中表达量最高,在乳腺癌stageⅠ期至stageⅡ期中表达量呈下降趋势(P=0.0494)。以中位数划分,CBLC高表达组乳腺癌患者的生存率高于低表达组(P=0.054)。CBLC过表达能够抑制乳腺癌细胞增殖和迁移。结论CBLC在乳腺癌各分型分期中的表达具有显著差异,其在低恶性的Luminal A分子分型、高分化型的黏液癌组织病理分型、早期乳腺癌中高表达,与乳腺癌患者生存良好呈正相关,可抑制乳腺癌细胞的增殖和迁移,可能是新的乳腺癌分子诊断或靶向治疗的潜在靶标。

Objective To provide a new monitoring index for clinical diagnosis and prognosis evaluation of breast cancer,and to provide a guiding theoretical basis for further research and treatment program formulation of breast cancer by studying the expression of Cbl Proto-Oncogene C(CBLC)in breast cancer.Methods The gene expression spectrum matrix(FPKM)of 1104 breast cancer tissues and 113 adjacent tissues were downloaded from TCGA of USCS Xena(https://xenabrowser.net).The expression differences of CBLC gene in breast cancer molecular classification,histopathological type,TNM stages and tumor stages and the relationship of prognosis were analyzed.The expression of CBLC in 30 tumor tissues or para-carcinoma tissues were observed by immunohistochemical staining.MCF7 breast cancer cells were used for scratch test,Transwell test and CCK-8 test,and the effects of CBLC on proliferation and migration were observed.Results The expression level(P=2.31×10^-20)and H-Score(P=0.014)of CBLC in the breast cancer group was higher than that in the para-carcinoma group.CBLC expression in Luminal A(P=1.68×10^-4)and mucinous carcinoma(P=4.00×10^-5)breast cancer was the highest among different breast cancer molecular types(P=1.68×10^-4).The expression level of CBLC decreased from stageⅠto stageⅡin breast cancer(P=0.0494).The survival rate of breast cancer patients in the high CBLC expression group was higher than that in the low CBLC expression group on a median basis(P=0.054).The high expression group of CBLC could inhibit the proliferation and migration of breast cancer cells.Conclusion The expression of CBLC in various breast cancer types and stages is significantly different,and it mainly expresses in Luminal A breast cancer which is low malignant molecular type,mucinous carcinoma which is high differentiated histopathological type and early breast cancer.It is positively correlated with survival and prognosis of breast cancer patients,and it can inhibit the migration and proliferation of breast cancer.CBLC may be a potential target for new molecular diagnosis or targeted treatment of breast cancer.