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Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas.

Faria M, Capinha L, Simões-Pereira J, Bugalho MJ, Silva AL - Int J Endocrinol (2016)

Bottom Line: Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC) is associated with an unfavorable prognosis.RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas.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.

View Article: PubMed Central - PubMed

Affiliation: Unidade de Investigação de Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, 1099-023 Lisboa, Portugal.

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.

No MeSH data available.


Related in: MedlinePlus

RAC1b expression in follicular thyroid tumors. (a) Expression levels of RAC1b among FTCs (n = 23) and FTAs (n = 33). RAC1b expression levels, quantified by qRT-PCR, correspond to arbitrary units representing fold differences relative to the reference sample; the threshold value defining RAC1b overexpression was set at 2.133 (corresponding to the mean plus two standard deviations of RAC1b expression level in a set of normal thyroid tissue samples). (b) Comparative analysis of RAC1b overexpression (RAC1b+) between follicular thyroid carcinomas (FTC) and follicular thyroid adenomas (FTA). (c) Western blot analysis of RAC1b protein levels in normal thyroid (N) and RAC1b overexpressing (T+) and nonoverexpressing (T−) tumors; protein molecular weight marker (M). (d) Association of RAC1b overexpression (RAC1b+) with clinical outcome (Group I: NED: no evidence of disease, BED: biochemical evidence of disease; Group II: SED: structural evidence of disease, D: death due to disease). (e) Association of RAC1b overexpression (RAC1b+) with the presence (M1) or absence (M0) of distant metastases.
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fig1: RAC1b expression in follicular thyroid tumors. (a) Expression levels of RAC1b among FTCs (n = 23) and FTAs (n = 33). RAC1b expression levels, quantified by qRT-PCR, correspond to arbitrary units representing fold differences relative to the reference sample; the threshold value defining RAC1b overexpression was set at 2.133 (corresponding to the mean plus two standard deviations of RAC1b expression level in a set of normal thyroid tissue samples). (b) Comparative analysis of RAC1b overexpression (RAC1b+) between follicular thyroid carcinomas (FTC) and follicular thyroid adenomas (FTA). (c) Western blot analysis of RAC1b protein levels in normal thyroid (N) and RAC1b overexpressing (T+) and nonoverexpressing (T−) tumors; protein molecular weight marker (M). (d) Association of RAC1b overexpression (RAC1b+) with clinical outcome (Group I: NED: no evidence of disease, BED: biochemical evidence of disease; Group II: SED: structural evidence of disease, D: death due to disease). (e) Association of RAC1b overexpression (RAC1b+) with the presence (M1) or absence (M0) of distant metastases.

Mentions: Total RAC1 and RAC1b expression levels were assessed by RT-qPCR. No significant differences in total RAC1 levels were found between FTCs and FTAs samples. RAC1b expression levels in tumor samples were obtained following normalization to the levels from a pool of normal thyroid tissues used as reference sample in all RT-qPCR assays. The mean level for RAC1b expression was significantly higher in FTCs (2.137 ± 0.5515) compared to FTAs (0.9656 ± 0.07342) (P value = 0.0152, two-tailed Student's t-test), corresponding to a 2.2 mean fold increase in the levels of RAC1b expression (Figure 1(a)).


Extending the Impact of RAC1b Overexpression to Follicular Thyroid Carcinomas.

Faria M, Capinha L, Simões-Pereira J, Bugalho MJ, Silva AL - Int J Endocrinol (2016)

RAC1b expression in follicular thyroid tumors. (a) Expression levels of RAC1b among FTCs (n = 23) and FTAs (n = 33). RAC1b expression levels, quantified by qRT-PCR, correspond to arbitrary units representing fold differences relative to the reference sample; the threshold value defining RAC1b overexpression was set at 2.133 (corresponding to the mean plus two standard deviations of RAC1b expression level in a set of normal thyroid tissue samples). (b) Comparative analysis of RAC1b overexpression (RAC1b+) between follicular thyroid carcinomas (FTC) and follicular thyroid adenomas (FTA). (c) Western blot analysis of RAC1b protein levels in normal thyroid (N) and RAC1b overexpressing (T+) and nonoverexpressing (T−) tumors; protein molecular weight marker (M). (d) Association of RAC1b overexpression (RAC1b+) with clinical outcome (Group I: NED: no evidence of disease, BED: biochemical evidence of disease; Group II: SED: structural evidence of disease, D: death due to disease). (e) Association of RAC1b overexpression (RAC1b+) with the presence (M1) or absence (M0) of distant metastases.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4835645&req=5

fig1: RAC1b expression in follicular thyroid tumors. (a) Expression levels of RAC1b among FTCs (n = 23) and FTAs (n = 33). RAC1b expression levels, quantified by qRT-PCR, correspond to arbitrary units representing fold differences relative to the reference sample; the threshold value defining RAC1b overexpression was set at 2.133 (corresponding to the mean plus two standard deviations of RAC1b expression level in a set of normal thyroid tissue samples). (b) Comparative analysis of RAC1b overexpression (RAC1b+) between follicular thyroid carcinomas (FTC) and follicular thyroid adenomas (FTA). (c) Western blot analysis of RAC1b protein levels in normal thyroid (N) and RAC1b overexpressing (T+) and nonoverexpressing (T−) tumors; protein molecular weight marker (M). (d) Association of RAC1b overexpression (RAC1b+) with clinical outcome (Group I: NED: no evidence of disease, BED: biochemical evidence of disease; Group II: SED: structural evidence of disease, D: death due to disease). (e) Association of RAC1b overexpression (RAC1b+) with the presence (M1) or absence (M0) of distant metastases.
Mentions: Total RAC1 and RAC1b expression levels were assessed by RT-qPCR. No significant differences in total RAC1 levels were found between FTCs and FTAs samples. RAC1b expression levels in tumor samples were obtained following normalization to the levels from a pool of normal thyroid tissues used as reference sample in all RT-qPCR assays. The mean level for RAC1b expression was significantly higher in FTCs (2.137 ± 0.5515) compared to FTAs (0.9656 ± 0.07342) (P value = 0.0152, two-tailed Student's t-test), corresponding to a 2.2 mean fold increase in the levels of RAC1b expression (Figure 1(a)).

Bottom Line: Previous studies from our group lead to the evidence that its overexpression in papillary thyroid carcinoma (PTC) is associated with an unfavorable prognosis.RAC1b was found to be overexpressed in 33% of carcinomas while no RAC1b overexpression was documented among follicular adenomas.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.

View Article: PubMed Central - PubMed

Affiliation: Unidade de Investigação de Patobiologia Molecular, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, 1099-023 Lisboa, Portugal.

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.

No MeSH data available.


Related in: MedlinePlus