Quantification of insulin receptor mRNA splice variants as a diagnostic tumor marker in breast cancer

Quantification of insulin receptor mRNA splice variants as a diagnostic tumor marker in breast cancer
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DOI:
10.3233/cbm-150505
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发表时间:
2015-01-01
期刊:
影响因子:
3.1
通讯作者:
Ahmed, Altayeb Abdalla
Ahmed, Altayeb Abdalla
中科院分区:
医学3区
文献类型:
--
作者:
Aljada, Ahmad;Saleh, Ayman M.;Ahmed, Altayeb Abdalla

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背景:成熟的人胰岛素受体(INSR)有两种亚型:A亚型和B亚型。目的:建立INSR转录本变异体的定量PCR检测方法,并将其作为乳腺癌诊断的肿瘤标志物。方法:采用TaqMan qRT-PCR技术,在市售的Breast Cancer Disease cDNA和Cancer Survey cDNA芯片中检测IR-A和IR-B的差异表达。乳腺癌组织中IR-A mRNA表达水平显著高于正常乳腺组织,而IR-B mRNA表达水平显著下调。根据转移阶段将患者分组表明,临床阶段(CS)-IV中IR-A mRNA水平在统计学上显著较高,CS-IIA、CS-IIIB和CS-IIIC中IR-B水平较低。然而,IR-A:IR-B比值在所有阶段均显示出统计学显著性增加。Cancer Survey cDNA阵列显示乳腺癌、肝癌和肺癌中IR-B mRNA水平较低,而IR-A表达在肾癌中显著改变,IR-A:IR-B ratio.CONCLUSIONS:结果表明在乳腺癌的所有临床阶段,IR-A:IR-B比率均增加。因此,IR-A:IR-B比值可能在乳腺癌中具有诊断生物标志物效用。
BACKGROUND: The mature human insulin receptor (INSR) has two isoforms: The A isoform and the B isoform. INSR upregulation has been suggested to play a role in cancer.OBJECTIVE: To establish quantitative PCR method for INSR transcript variants and examine their differential expression as a diagnostic tumor marker in breast cancer.METHODS: The differential expression of IR-A and IR-B were evaluated by TaqMan qRT-PCR assay in the commercially available Breast Cancer Disease cDNA and Cancer Survey cDNA arrays.RESULTS: The mRNA expression levels of IR-A was statistically significantly higher in breast cancer when compared to normal breast tissue while IR-B mRNA expression was down regulated significantly in breast cancer. Stratification of patients into groups according to metastatic stages indicated statistically significantly higher levels of IR-A mRNA in clinical stage (CS)-IV, and lower IR-B levels in CS-IIA, CS-IIIB and CS-IIIC. However, IR-A: IR-B ratio showed a statistically significant increase in all stages. Cancer Survey cDNA array demonstrated lower levels of IR-B mRNA in breast adenocarcinoma, liver carcinoma and lung carcinoma only while IR-A expression was significantly altered in kidney carcinoma without any significant differences in IR-A: IR-B ratios.CONCLUSIONS: The results demonstrate an increased IR-A: IR-B ratio in all clinical stages of breast cancer. Thus, IR-A: IR-B ratio may have a diagnostic biomarker utility in breast cancer.