McKiernan Eadaoin, McDermott Enda W, Evoy Dennis, Crown John, Duffy Michael J
Department of Pathology and Laboratory Medicine, St Vincent's University Hospital, Dublin 4, Ireland.
Tumour Biol. 2011 Jun;32(3):441-50. doi: 10.1007/s13277-010-0137-2. Epub 2010 Dec 14.
The S100 gene family encode low molecular weight proteins implicated in cancer progression. In this study, we analyzed the expression of four S100 genes in one cohort of patients with breast cancer and 16 S100 genes in a second cohort. In both cohorts, the expression of S100A8 and S1009 mRNA level was elevated in high-grade compared to low-grade tumors and in estrogen receptor-negative compared to estrogen receptor-positive tumors. None of the S100 transcripts investigated were significantly associated with the presence of lymph node metastasis. Notably, multiple S100 genes, including S100A1, S100A2, S100A4, S100A6, S100A8, S100A9, S100A10, S100A11, and S100A14 were upregulated in basal-type breast cancers compared to non-basal types. Using Spearman's correlation analysis, several S100 transcripts correlated significantly with each other, the strongest correlation has been found between S100A8 and S100A9 (r = 0.889, P < 0.001, n = 295). Of the 16 S100 transcripts investigated, only S100A11 and S100A14 were significantly associated with patient outcome. Indeed, these two transcripts predicted outcome in the cohort of patients that did not receive systemic adjuvant therapy. Based on our findings, we conclude that the different S100 genes play varying roles in breast cancer progression. Specific S100 genes are potential targets for the treatment of basal-type breast cancers.
S100基因家族编码与癌症进展相关的低分子量蛋白质。在本研究中,我们分析了一组乳腺癌患者中4个S100基因的表达情况以及另一组患者中16个S100基因的表达情况。在这两组患者中,与低级别肿瘤相比,高级别肿瘤中S100A8和S100A9 mRNA水平升高;与雌激素受体阳性肿瘤相比,雌激素受体阴性肿瘤中S100A8和S100A9 mRNA水平升高。所研究的S100转录本均与淋巴结转移的存在无显著相关性。值得注意的是,与非基底型乳腺癌相比,包括S100A1、S100A2、S100A4、S100A6、S100A8、S100A9、S100A10、S100A11和S100A14在内的多个S100基因在基底型乳腺癌中上调。使用Spearman相关性分析,多个S100转录本之间存在显著相关性,其中S100A8和S100A9之间的相关性最强(r = 0.889,P < 0.001,n = 295)。在所研究的16个S100转录本中,只有S100A11和S100A14与患者预后显著相关。事实上,这两个转录本可预测未接受全身辅助治疗患者队列的预后。基于我们的研究结果,我们得出结论,不同的S100基因在乳腺癌进展中发挥着不同的作用。特定的S100基因是治疗基底型乳腺癌的潜在靶点。