Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas

Abstract

RAC1b is a hyperactive variant of the small GTPase RAC1 known to be a relevant molecular player in different cancers. Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC) is associated with an unfavorable prognosis. In the present study, we intended to extend the analysis of RAC1b expression to thyroid follicular neoplasms and to seek for clinical correlations. RAC1b expression levels were determined by RT-qPCR in thyroid follicular tumor samples comprising 23 follicular thyroid carcinomas (FTCs) and 33 follicular thyroid adenomas (FTAs). RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas. Patients with a diagnosis of FTC were divided into two groups based on longitudinal evolution and final outcome. RAC1b overexpression was significantly associated with both the presence of distant metastases (P = 0.01) and poorer clinical outcome (P = 0.01) suggesting that, similarly to that previously found in PTCs, RAC1b overexpression in FTCs is also associated with worse outcomes. Furthermore, the absence of RAC1b overexpression in follicular adenomas hints its potential as a molecular marker likely to contribute, in conjunction with other putative markers, to the preoperative differential diagnosis of thyroid follicular lesions.

RAC1b overexpression stimulates proliferation and NF-kB-mediated anti-apoptotic signaling in thyroid cancer cells

“…Nonetheless our data indicate that during the malignant progression of some thyroid tumors the arising of RAC1b overexpression may suffice to offer tumor cells an additional survival advantage through NF-kB stimulation. This, in turn, can lead to more aggressive phenotypes and poorer clinical outcomes, as reported in both PTCs and FTCs [ 8 , 28 ].…”

RAC1B: A Rho GTPase with Versatile Functions in Malignant Transformation and Tumor Progression

“…Whereas BRAF-V600E alone did not associate with patient outcome, the association of RAC1B overexpression with BRAF-V600E was overrepresented in the group with poorer clinical outcome. These data suggest that RAC1B and B-RAF-V600E may interact to worsen the prognosis of PTC patients [72,73].…”

Rho signaling: An historical and evolutionary perspective

“…Exons encoding the 19 a.a. peptide were found exclusively in the genomes of Amniotes (Boureux et al, 2007). Although reports have documented the role of Rac1b in the progression of many cancer types (listed in Faria et al, 2016), the normal function of this isoform remains unknown.…”