Bellizzi Antonia, Mangia Anita, Chiriatti Annalisa, Petroni Stella, Quaranta Michele, Schittulli Francesco, Malfettone Andrea, Cardone Rosa Angela, Paradiso Angelo, Reshkin Stephan Joel
Clinical Experimental Oncology Laboratory, National Cancer Institute Giovanni Paolo II, Bari, Italy.
Int J Mol Med. 2008 Jul;22(1):25-31.
RhoA protein is over-expressed in breast cancer and other solid tumors and has been used in tumor biopsies as a quantitative tumor marker for progression, stage and prognosis in molecular detection strategies. Measuring protein markers in plasma or blood cells is preferred to tumor biopsies as it represents a minimally invasive, repeatable measurement that can be followed over time. In this study we evaluated the hypothesis that quantitative RhoA protein expression in circulatory lymphocytes is identically associated with the same tumor clinico-pathological features found in biopsies. RhoA protein levels were analyzed by Western blotting in circulating lymphocytes isolated from 52 consecutive patients with breast cancer and in 34 paired breast tumor biopsies from the same case study, and compared with the following clinico-pathological features of the patients: histological grade, tumor size, steroid receptor status, lymphonode status, proliferative activity and prognosis [Nottingham Prognostic Index (NPI)]. We observed that the level of circulatory, peripheral lymphocyte RhoA expression reflected that found in the matched biopsy of the same patient. Furthermore, similarly to previous reports regarding breast cancer tissue biopsies, the level of RhoA protein expression in both biopsies and in circulatory lymphocytes was positively associated with tumor size, grade, proliferative activity of the tumor biopsy and NPI, while there was no significant association of RhoA protein expression with either estrogen- or progesterone-receptor expression. Our study demonstrated that the association of lymphocyte RhoA protein expression with classical clinico-pathological parameters closely corresponded with that observed for RhoA protein expression in the tumor biopsies. We propose that measurement of RhoA expression in the circulatory lymphocytes of breast cancer patients can be used to predict breast cancer occurrence, progression and prognosis and may prove valuable in the management of cancer patients.
RhoA蛋白在乳腺癌和其他实体瘤中过度表达，并已在肿瘤活检中用作分子检测策略中进展、分期和预后的定量肿瘤标志物。与肿瘤活检相比，在血浆或血细胞中测量蛋白质标志物更受青睐，因为它代表了一种微创、可重复的测量方法，并且可以随时间进行跟踪。在本研究中，我们评估了以下假设：循环淋巴细胞中RhoA蛋白的定量表达与活检中发现的相同肿瘤临床病理特征密切相关。通过蛋白质印迹法分析了从52例连续乳腺癌患者中分离出的循环淋巴细胞以及来自同一病例研究的34对乳腺肿瘤活检组织中的RhoA蛋白水平，并将其与患者的以下临床病理特征进行比较：组织学分级、肿瘤大小、类固醇受体状态、淋巴结状态、增殖活性和预后[诺丁汉预后指数（NPI）]。我们观察到，循环外周淋巴细胞RhoA表达水平反映了同一患者匹配活检中的表达水平。此外，与先前关于乳腺癌组织活检的报道相似，活检组织和循环淋巴细胞中RhoA蛋白表达水平均与肿瘤大小、分级、肿瘤活检的增殖活性和NPI呈正相关，而RhoA蛋白表达与雌激素或孕激素受体表达均无显著相关性。我们的研究表明，淋巴细胞RhoA蛋白表达与经典临床病理参数之间的关联与肿瘤活检中观察到的RhoA蛋白表达密切对应。我们建议，测量乳腺癌患者循环淋巴细胞中的RhoA表达可用于预测乳腺癌的发生、进展和预后，并且可能在癌症患者的管理中具有重要价值。
