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利用 CDH1、CDH13、CD44 和 TIMP3 基因表达预测原发性乳腺癌的侵袭表型。

Predicting invasive phenotype with CDH1, CDH13, CD44, and TIMP3 gene expression in primary breast cancer.

机构信息

Department of Basic Oncology, Dokuz Eylül University, Izmir, Turkiye.

出版信息

Cancer Sci. 2009 Dec;100(12):2341-5. doi: 10.1111/j.1349-7006.2009.01333.x. Epub 2009 Sep 1.

Abstract

We aimed to determine changes in the expression of the genes CDH1, CDH13, CD44, and TIMP3 to look for any relationship between them, HER2 and ESR1 expression at the RNA level, and the histopathological properties of tumors. We also analyzed the expression properties of double-negative (estrogen receptor [ER] and human epidermal growth factor receptor [HER2] both negative) breast tumors. Expression status was studied in fresh tissue at the mRNA level with quantitative PCR using hydrolysis probes. Sixty-two cancer patients and four normal controls were included in the study. When the tumor group was analyzed as a whole, the correlations of ESR1 with CDH1, CDH13, and TIMP3 were P < 0.05, P < 0.005, and P < 0.005, respectively. In ER-positive tumors, CDH1 and CDH13 were correlated directly (P < 0.005) when HER2 was correlated with CDH1, CDH13, and TIMP3 indirectly (P < 0.005, P < 0.005, and P < 0.05, respectively). CDH1 and CD44 had a strong indirect correlation (P < 0.005) in ER-negative tumors. There were significant differences in the expression levels of the CDH13, TIMP3, and CD44 genes (P < 0.005, P < 0.005, and P < 0.05, respectively) between the ER-positive and -negative groups. All four genes were found to be correlated with invasive properties in both ER-positive and -negative tumors. In double-negative tumor samples, only CD44 had a significant and strong correlation with stage, lymph node involvement, and metastasis (P < 0.05, P < 0.005, and P < 0.05, respectively). As a conclusion, a decrease in CDH1, CDH13, and TIMP3 expression levels with an increase in CD44 can be used as an indicator for invasion in both ER-positive and -negative breast tumors. In double-negative tumor tissues, CD44 can be considered a marker for aggressive properties.

摘要

我们旨在确定基因 CDH1、CDH13、CD44 和 TIMP3 的表达变化,寻找它们之间、HER2 和 ESR1 在 RNA 水平上的表达以及肿瘤组织病理学特性之间的关系。我们还分析了双阴性(雌激素受体[ER]和人表皮生长因子受体[HER2]均为阴性)乳腺癌的表达特性。使用水解探针的定量 PCR 检测新鲜组织中的表达状态。本研究纳入了 62 名癌症患者和 4 名正常对照者。当将肿瘤组作为一个整体进行分析时,ESR1 与 CDH1、CDH13 和 TIMP3 的相关性分别为 P<0.05、P<0.005 和 P<0.005。在 ER 阳性肿瘤中,当 HER2 与 CDH1、CDH13 和 TIMP3 间接相关时,CDH1 和 CDH13 直接相关(P<0.005)(P<0.005、P<0.005 和 P<0.05)。在 ER 阴性肿瘤中,CDH1 和 CD44 之间存在很强的间接相关性(P<0.005)。在 CDH13、TIMP3 和 CD44 基因的表达水平上,ER 阳性和阴性组之间存在显著差异(P<0.005、P<0.005 和 P<0.05)。在 ER 阳性和阴性肿瘤中,这四个基因均与侵袭性相关。在双阴性肿瘤样本中,只有 CD44 与分期、淋巴结受累和转移有显著且强烈的相关性(P<0.05、P<0.005 和 P<0.05)。综上所述,CDH1、CDH13 和 TIMP3 表达水平的降低和 CD44 的增加可作为 ER 阳性和阴性乳腺癌侵袭性的指标。在双阴性肿瘤组织中,CD44 可作为侵袭性的标志物。

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