Circulating MicroRNA Profiles as Potential Biomarkers for differentiated thyroid cancer recurrence

2022 ◽  
Author(s):  
Jelena Jankovic Miljus ◽  
María Augusta Guillén-Sacoto ◽  
Jennifer Makiadi-Alvarado ◽  
León Wert-Lamas ◽  
Julia Ramirez-Moya ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Housekeeping Genes ◽  
Human Thyroid ◽  
Circulating Microrna ◽  
Sequencing Data ◽  
Serum Samples ◽  
Persistent Disease ◽  
Cancer Pathogenesis ◽  
Before And After

Abstract Context Circulating microRNAs (miRNAs) are emerging biomarkers of thyroid cancer. Objective This study sought to identify the profile of circulating miRNAs and its response to human recombinant TSH (rhTSH) in thyroid cancer patients with recurrent/persistent disease. Methods We obtained serum samples from 30 patients with differentiated thyroid cancer, 14 with recurrent/persistent disease and 16 with complete remission. We used next generation sequencing to define the miRnomes along with a comprehensive qPCR validation using two different platforms. We made a transversal study by comparing serum miRNA profiles of patients with or without recurrent/persistent disease and a longitudinal study looking at differences before and after rhTSH stimulation. Selected miRNAs were then studied in human thyroid cancer cell lines TPC-1, FTC-133 and OCUT-2 in response to TSH stimulation. Results We could not demonstrate any consistent differences in serum profiles of known miRNAs between patients with and without recurrent/persistent disease or before and after rhTSH stimulation. However, our sequencing data revealed two putative novel miRNAs that rise with rhTSH stimulation in the serums of patients with recurrent/persistent disease. We further confirmed by qPCR the upregulation of these putative miRNAs both in serums and in TSH-stimulated cells. We also show miRNAs that are good candidates for housekeeping genes in the serum of patients independently of the levels of TSH. Conclusions The present study does not provide evidence that known miRNAs can be used as circulating markers for recurrence of thyroid cancer. However, we suggest that novel miRNA molecules may be related to thyroid cancer pathogenesis.

scholarly journals Utility of recombinant human TSH stimulation test in the follow-up of patients with differentiated thyroid cancer depending on basal thyroglobulin results

2020 ◽  
Vol 1 (1) ◽  
Author(s):  
Amaia Sandúa ◽  
Monica Macias ◽  
Carolina Perdomo ◽  
Juan Carlos Galofre ◽  
Roser Ferrer ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
High Sensitivity ◽  
Thyroid Stimulating Hormone ◽  
Stimulation Test ◽  
Human Thyroid ◽  
Antithyroglobulin Antibodies ◽  
Structural Disease

AbstractBackgroundThyroglobulin (Tg) is fundamental for differentiated thyroid cancer (DTC) monitoring. Tg detection can be enhanced using recombinant human thyroid-stimulating hormone (TSH) (rhTSH). This study is aimed to evaluate the use of the rhTSH stimulation test when using a high-sensitivity Tg assay.MethodsWe retrospectively studied 181 rhTSH tests from 114 patients with DTC and negative for antithyroglobulin antibodies (anti-TgAb). Image studies were performed in all cases. Serum Tg and anti-TgAb were measured using specific immunoassays.ResultsrhTSH stimulation in patients with basal serum Tg (b-Tg) concentrations lower than 0.2 ng/mL always resulted in rhTSH-stimulated serum Tg (s-Tg) concentrations lower than 1.0 ng/mL and negative structural disease. In patients with b-Tg concentration between 0.2 and 1.0 ng/mL, s-Tg detected one patient (1/30) who showed biochemical incomplete response. Patients with negative images had lower s-Tg than those with nonspecific or abnormal findings (p<0.05). Receiver operating characteristic curve analysis of the s-Tg to detect altered images showed an area under the curve of 0.763 (p<0.05). With an s-Tg cutoff of 0.85 ng/mL, the sensitivity was 100%, decreasing to 96.15% with an s-Tg cutoff of 2 ng/mL.ConclusionsPatients with DTC with b-Tg concentrations equal or higher than 0.2 ng/mL can benefit from the rhTSH stimulation test.

scholarly journals Circulating microRNA Expression in Cushing’s Syndrome

2021 ◽  
Vol 12 ◽  
Author(s):  
Sharmilee Vetrivel ◽  
Ru Zhang ◽  
Mareen Engel ◽  
Barbara Altieri ◽  
Leah Braun ◽  
...  
Keyword(s):  
Cushing’S Syndrome ◽  
Validation Cohort ◽  
Cushing's Syndrome ◽  
Circulating Microrna ◽  
High Morbidity ◽  
Discovery Cohort ◽  
Serum Samples ◽  
Curative Surgery ◽  
Before And After ◽  
Diagnosis And Classification

ContextCushing’s syndrome (CS) is a rare disease of endogenous hypercortisolism associated with high morbidity and mortality. Diagnosis and classification of CS is still challenging.ObjectiveCirculating microRNAs (miRNAs) are minimally invasive diagnostic markers. Our aim was to characterize the circulating miRNA profiles of CS patients and to identify distinct profiles between the two major CS subtypes.MethodsWe included three groups of patients from the German Cushing’s registry: ACTH-independent CS (Cortisol-Producing-Adenoma; CPA), ACTH-dependent pituitary CS (Cushing’s Disease; CD), and patients in whom CS had been ruled out (controls). Profiling of miRNAs was performed by next-generation-sequencing (NGS) in serum samples of 15 CS patients (each before and after curative surgery) and 10 controls. Significant miRNAs were first validated by qPCR in the discovery cohort and then in an independent validation cohort of 20 CS patients and 11 controls.ResultsNGS identified 411 circulating miRNAs. Differential expression of 14 miRNAs were found in the pre- and postoperative groups. qPCR in the discovery cohort validated 5 of the significant miRNAs from the preoperative group analyses. Only, miR-182-5p was found to be significantly upregulated in the CD group of the validation cohort. Comparing all CS samples as a group with the controls did not reveal any significant differences in expression.OutcomeIn conclusion, our study identified miR-182-5p as a possible biomarker for CD, which has to be validated in a prospective cohort. Furthermore, our results suggest that presence or absence of ACTH might be at least as relevant for miRNA expression as hypercortisolism itself.

scholarly journals BRAF V600E Status and Stimulated Thyroglobulin at Ablation Time Increase Prognostic Value of American Thyroid Association Classification Systems for Persistent Disease in Differentiated Thyroid Carcinoma

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Andrea Repaci ◽  
Valentina Vicennati ◽  
Alexandro Paccapelo ◽  
Ottavio Cavicchi ◽  
Nicola Salituro ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Risk Stratification ◽  
Prognostic Value ◽  
Differentiated Thyroid Cancer ◽  
Risk Classification ◽  
Classification Systems ◽  
Braf V600e ◽  
American Thyroid Association ◽  
Persistent Disease ◽  
Ablation Time

Background. Stimulated thyroglobulin levels measured at the time of remnant ablation (A-hTg) and BRAFV600E mutation had shown prognostic value in predicting persistent disease in differentiated thyroid cancer (DTC). The aim of this study was to evaluate the prognostic role of A-hTg combined with the BRAFV600E status in association with the revised American Thyroid Association (ATA) risk stratification. Material and Methods. 620 patients treated for a DTC were included in this study with a median follow-up duration of 6.1 years. All patients underwent total thyroidectomy followed by radioiodine ablation. Patients with positive anti-thyroglobulin antibodies were excluded. The predictive value of A-hTg was calculated by receiver operating characteristic curve (ROC curve) analysis. The Cox proportional hazard regression model, including the BRAF status, A-hTg, and ATA classification system, was assessed to evaluate the existing persistent disease risk. Results. Taken together, the BRAF status and A-hTg levels improve the ATA risk classification in all categories. In particular, in the low-risk ATA classification, only the combination of BRAFV600E+A-hTg>8.9ng/ml was associated with persistent disease (P=0.001, HR 60.2, CI 95% 5.28-687). In the intermediate-risk ATA classification, BRAFWT+A-hTg>8.9ng/ml was associated with persistent disease (P=0.029, HR 2.71, CI 95% 1.106-6.670) and BRAFV600E+A-hTg>8.9ng/ml was also associated with persistent disease (P<0.001, HR 5.001, CI 95% 2.318-10.790). In the high-risk ATA classification, both BRAFV600E+A-hTg<8.9ng/ml and BRAFV600E+A-hTg>8.9 ng/ml were associated with persistent disease (P=0.042, HR 5.963, CI 95% 1.069-33.255 and P=0.002, HR 11.564, CI 95% 2.543-52.576, respectively). Conclusions. The BRAF status and stimulated thyroglobulin levels at ablation time improve the ATA risk stratification of differentiated thyroid cancer; therefore, even A-hTg could be included in risk classification factors.

scholarly journals A Randomized Controlled Trial for the Effectiveness of Aromatherapy in Decreasing Salivary Gland Damage following Radioactive Iodine Therapy for Differentiated Thyroid Cancer

2016 ◽  
Vol 2016 ◽  
pp. 1-6 ◽  
Author(s):  
Michihiro Nakayama ◽  
Atsutaka Okizaki ◽  
Koji Takahashi
Keyword(s):  
Thyroid Cancer ◽  
Salivary Gland ◽  
Differentiated Thyroid Cancer ◽  
Radioactive Iodine ◽  
Control Group ◽  
Parotid Glands ◽  
Before And After ◽  
Group A ◽  
Gland Function ◽  
Group B

Objective. The aim of this study was to investigate effects of aromatherapy in decreasing salivary gland damage for patients undergoing radioactive iodine (RAI) therapy with differentiated thyroid cancer (DTC). Materials and Methods. The subjects were 71 patients with DTC. They were divided into aromatherapy group (group A, n=35) and a control group (group B, n=36). We blended 1.0 mL of lemon and 0.5 mL of ginger essential oils. The patients in the inhalation aromatherapy group inhaled this blend oil and those in the control group inhaled distilled water as placebo for 10 min during admission. We statistically compared salivary gland function before and after treatment between groups A and B. Results. In comparison with group B, the rate of change of the accumulation rate was significantly higher in the parotid glands and submandibular glands of group A (P<0.05). In comparison with group B, a significant increase in rate of secretion change before and after treatment was noted in the bilateral parotid glands in group A (P<0.05). Conclusion. Because an amelioration of salivary gland function was observed in the present study, our results suggest the efficacy of aromatherapy in the prevention of treatment-related salivary gland disorder. This trial is registered with UMIN Clinical Trial Registry: UMIN000013968.

scholarly journals Early post-treatment risk stratification of differentiated thyroid cancer: comparison of three high-sensitive Tg assays

2018 ◽  
Vol 178 (1) ◽  
pp. 75-82 ◽  
Author(s):  
Luca Giovanella ◽  
Mauro Imperiali ◽  
Frederik A Verburg ◽  
Pierpaolo Trimboli
Keyword(s):  
Thyroid Cancer ◽  
Diagnostic Performance ◽  
Differentiated Thyroid Cancer ◽  
Receiver Operating Characteristics ◽  
Operating Characteristics ◽  
Serum Samples ◽  
Treatment Risk ◽  
Radioiodine Ablation ◽  
Highly Sensitive ◽  
Over Time

ObjectiveTo assess the diagnostic performance of three high-sensitive assays in a cohort of TgAb-negative and TgAb-positive differentiated thyroid cancer (DTC) patients.DesignRetrospective study on prospectively selected DTC patients.MethodsSerum samples from 154 DTC patients were obtained 6–12 months after radioiodine ablation and tested by Beckman, Roche, BRAHMS Tg and TgAb assays, respectively. Receiver operating characteristics curves for Tg were plotted using outcome over time as benchmark and assay-specific Tg thresholds were obtained for TgAb-negative and TgAb-positive patients.ResultsThe frequency of positive TgAb was 21, 20 and 20% for Beckman, Roche and BRAHMS, respectively. In TgAb-negative patients, clinical sensitivities and specificities of 100% and 85–95%, respectively, were observed across all assays. In TgAb-positive patients, clinical sensitivities and specificities of 80–100% and 92–96%, respectively, were observed using lower thresholds than in patients without TgAb.ConclusionsAdopting appropriate thresholds, lower than those for TgAb-negative patients, is possible to reliably follow TgAb-positive patients using highly sensitive Tg assays.

scholarly journals Microscopic Positive Tumor Margin Increases Risk for Disease Persistence but Not Recurrence in Patients with Stage T1-T2 Differentiated Thyroid Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Olfat Kamel Hasan ◽  
Sarah De Brabandere ◽  
Irina Rachinsky ◽  
David Laidley ◽  
Danielle MacNeil ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Recurrent Disease ◽  
Positive Margin ◽  
Disease Recurrence ◽  
Low Risk ◽  
Recurrence Rates ◽  
Persistent Disease ◽  
Positive Margins

Introduction. Differentiated thyroid cancer (DTC) has an overall excellent prognosis. Patients who develop recurrent disease have a more unfavorable disease course than those with no recurrence. Higher recurrence rates are seen with incomplete surgical resection and gross positive margins. It is unclear whether microscopic positive margin affects disease recurrence rates as much as grossly positive margin. Aim of the Study. To assess whether microscopic positive margin is an independent predictor of disease recurrence in patients with overall low-risk DTC. Patients and Methods. We conducted a retrospective single-center institutional review of 1,583 consecutive patients’ charts from 1995–2013 using the Canadian Thyroid Cancer Consortium Registry. We included adult patients with nonmetastasizing T1 and T2 DTC with a minimum of three years follow-up. Univariate and multivariate analyses were used to study factors that may influence the risk of persistent/recurrent disease. Strict definitions of persistent versus recurrent disease were applied. Results. 963 patients (152 men and 811 women) were included in the study with a mean age of 46 years. Microscopic positive margins were present in 12% of the specimens and were associated with an increased rate of persistent disease (8% versus 2% in the controls) but not with an increased risk of recurrent disease (1% in both groups). T2 tumors had a significantly higher incidence of positive margins than T1 tumors (48% versus 36%) and significantly higher nodal staging. Conclusions. Microscopic positive margin in the histopathology report in patients with low-risk DTC was associated with a higher rate of persistent disease but did not increase the risk of disease recurrence. A close follow-up of biomarkers and occult residual cancerous lesions is needed, especially in the first year. Further studies are needed to determine whether additional therapeutic measures to prevent recurrence are indicated in T1 and T2 DTC with positive microscopic surgical margins.

ISTHMUS TOPOGRAPHY IS A RISK FACTOR FOR PERSISTENT DISEASE IN PATIENTS WITH DIFFERENTIATED THYROID CANCER

2021 ◽  
Author(s):  
Alfredo Campennì ◽  
Rosaria Maddalena Ruggeri ◽  
Massimiliano Siracusa ◽  
Giulia Giacoppo ◽  
Flavia La Torre ◽  
...  
Keyword(s):  
Risk Factor ◽  
Thyroid Cancer ◽  
Differentiated Thyroid Cancer ◽  
Disease Free Survival ◽  
Initial Therapy ◽  
Response To Therapy ◽  
Rank Test ◽  
Additional Risk Factor ◽  
Persistent Disease ◽  
Incomplete Response

Aim: The risk of differentiated thyroid cancer (DTC) recurrence is widely evaluated according to the 2015 ATA Risk Stratification System. Topography of malignant nodules has been previously reported as an additional risk factor but is not included in the ATA system. Thus, our study aimed to evaluate the relationship between DTC topography and response to initial therapy. Patients and Methods: We enrolled 401 low- to intermediate-risk patients with DTC who had undergone thyroidectomy and radioiodine therapy. DTC topography was recorded and compared with the response to therapy as assessed 12 months after end of therapy. Results: Overall, 366/401 (91.3%) patients had an excellent response to initial therapy while 22/401 (5.5%) and 13/401 (3.2%) had incomplete biochemical or structural response, respectively. Incomplete response occurred in 10/36 (27.8%), 5/125 (4.0%), and 4/111 (3.6%) patients whose unifocal malignant nodules were located in the isthmus, right lobe, or left lobe. Incomplete response was also observed in 4/54 (7.4%) and 12/75 (16%) patients carrying multifocal cancers in one or both lobes, respectively. Patients with isthmic cancer more frequently demonstrated incomplete response compared with those who had cancer in other locations (p=0.00). No significant relationship was found with age, gender, maximum size of malignant nodule, Hashimoto’s thyroiditis, vascular invasion, and extrathyroidal extension (p=0.78, p=0.77, p=0.52, p=0.19, p=0.73, and p=0.26, respectively). The risk of incomplete response was about 65% higher in patients with isthmic lesions compared with other patients (odds ratio=6.725). A log-rank test demonstrated that disease-free survival (DFS) of patients with isthmic lesions was significantly shorter than that of other patients (p=0.02). Conclusion: Our data show that isthmus topography of malignant thyroid nodules is a risk factor for having both persistent disease 12 months after primary treatment and reduced DFS.

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