Nicolussi Arianna, D'Inzeo Sonia, Mincione Gabriella, Buffone Amelia, Di Marcantonio Maria Carmela, Cotellese Roberto, Cichella Annadomenica, Capalbo Carlo, Di Gioia Cira, Nardi Francesco, Giannini Giuseppe, Coppa Anna
Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy.
Department of Experimental and Clinical Sciences, 'G. d'Annunzio' University Foundation, Chieti-Pescara, Italy.
Int J Oncol. 2014 Feb;44(2):548-56. doi: 10.3892/ijo.2013.2208. Epub 2013 Dec 5.
Many clinical studies highlight the dichotomous role of PRDXs in human cancers, where they can exhibit strong tumor-suppressive or tumor-promoting functions. Recent evidence suggests that lower expression of PRDXs correlates with cancer progression in colorectal cancer (CRC) or in esophageal squamous carcinoma. In the thyroid, increased levels of PRDX1 has been described in follicular adenomas and carcinomas, as well as in thyroiditis, while reduced levels of PRDX6 has been found in follicular adenomas. We studied the expression of PRDX1 and PRDX6, in a series of thyroid tissue samples, covering different thyroid diseases, including 13 papillary thyroid carcinomas (PTCs). Our results show that PRDX1 and PRDX6 are significantly reduced in all PTCs compared to normal tissues, to non-neoplastic tissue (MNG) or follicular neoplasms. This reduction is strongly evident in PTCs harboring BRAF V600E (31% of our cases). Using TPC-1 and BCPAP and FRTL-5 cell lines, we demonstrate for the first time that the presence of BRAF V600E is responsible of the hypoexpression of PRDX1 and PRDX6 both at mRNA and protein levels. Finally, independently of BRAF status, we observe an interesting correlation between the tumor size, the presence of lymph node metastasis and the lowest PRDX1 and PRDX6 levels. Therefore, these data indicate that PRDX1 and PRDX6 expression not only may play a key role in papillary thyroid carcinogenesis via a BRAF V600E-dependent mechanism, but their determination could be considered as potential tumor marker for indicating tumor progression in PTCs, independently of BRAF status.
许多临床研究突出了PRDXs在人类癌症中的双重作用，它们在其中可表现出强大的肿瘤抑制或肿瘤促进功能。最近的证据表明，PRDXs的低表达与结直肠癌（CRC）或食管鳞状细胞癌的癌症进展相关。在甲状腺中，已报道PRDX1水平在滤泡性腺瘤、癌以及甲状腺炎中升高，而在滤泡性腺瘤中发现PRDX6水平降低。我们研究了一系列涵盖不同甲状腺疾病的甲状腺组织样本中PRDX1和PRDX6的表达，其中包括13例甲状腺乳头状癌（PTC）。我们的结果表明，与正常组织、非肿瘤组织（MNG）或滤泡性肿瘤相比，所有PTC中PRDX1和PRDX6均显著降低。这种降低在携带BRAF V600E的PTC中（占我们病例的31%）尤为明显。使用TPC-1、BCPAP和FRTL-5细胞系，我们首次证明BRAF V600E的存在在mRNA和蛋白质水平上均导致PRDX1和PRDX6的低表达。最后，独立于BRAF状态，我们观察到肿瘤大小、淋巴结转移的存在与最低的PRDX1和PRDX6水平之间存在有趣的相关性。因此，这些数据表明，PRDX1和PRDX6的表达不仅可能通过BRAF V600E依赖性机制在甲状腺乳头状癌发生中起关键作用，而且它们的检测可被视为指示PTC肿瘤进展的潜在肿瘤标志物，独立于BRAF状态。
