A gene expression signature that distinguishes malignant from benign thyroid nodules.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21011-e21011
Author(s):  
Song Tian ◽  
John DiCarlo ◽  
Jiaye Yu ◽  
George J Quellhorst ◽  
Raymond K Blanchard ◽  
...  

e21011 Background: Thyroid nodules can be detected in as high as 67% of the population. Distinguishing thyroid cancers from benign lesions is crucial for determining an appropriate treatment plan. For years a gene expression signature for discriminating malignant from benign thyroid nodules has been sought by clinicians. In this study, multivariate bioinformatics tools were used to generate a qPCR based gene expression signature for determining malignancy in thyroid nodules. Methods: Multiple mathematical models, such as Random Forest, Support Vector Machine (SVM), and Nearest Shrunken Centroid (NSC), were used to analyze published microarray data sets and select 366 putative classifier (biomarker) mRNA targets. The selected 366 genes were further evaluated for their expression pattern by real-time PCR using a panel of 49 pathology assessed thyroid nodule samples (fresh frozen, 23 malignant and 26 benign). Results: Using the qPCR data set, Random Forest was compared with SVM and NSC classifier methods and was found to be more successful in finding genes with better discriminative powers. A Random Forest method identified a panel of 7 genes together with 5 reference genes as a gene expression signature for thyroid malignancy, which led to the development of a companion classifying algorithm to provide a probability score to assess malignancy of thyroid nodules. In our limited sample set, this signature was shown to distinguish malignant and benign thyroid nodules with 92% accuracy and 100% specificity. Conclusions: Our results suggest that a combination of multiple bioinformatics analysis tools is the proper approach for biomarker candidate selection from high-throughput gene expression data. As demonstrated here, panel of 12 genes and a companion classification algorithm has the potential to successfully discriminate malignant thyroid nodule with high accuracy and specificity. This panel of twelve genes is for molecular biology applications only.

2019 ◽  
Vol 15 (36) ◽  
pp. 4167-4179 ◽  
Author(s):  
Jianqiu Liu ◽  
Xinyue Tang ◽  
Jing Lv ◽  
Xiaowei Peng ◽  
Ke Zhang ◽  
...  

Aim: To investigate the clinical roles of LINC00152 and SNHG12 in papillary thyroid carcinoma (PTC). Methods: LINC00152 and SNHG12 expression was sought and analysis in gene expression omnibus, The Cancer Genome Atlas and GEPIA datasets. Tumor and adjacent normal tissues were collected from 97 PTC and 44 benign thyroid nodules patients. The expression was evaluated by quantitative real-time polymerase chain reaction. The association between the expression level and clinicopathologic characteristics was analyzed by χ2 test. Receiver operating characteristic curves were plotted to evaluate the diagnostic value. Results: The expression of SNHG12 and LINC00152 were significantly higher in PTC tissues than in adjacent normal tissues not only in gene expression omnibus database but the validated samples. More interesting, LINC00152 expression level was also significantly higher in PTC tissues than that in benign thyroid nodules. The upregulation of LINC00152 and SNHG12 was associated with the malignant progression of PTC. Receiver operating characteristic curve analysis also demonstrated that there was a good trend, which indicates that they may have certain diagnostic value. Conclusion: LINC00152 and SNHG12 might serve as serve as potential related molecules of PTC.


2021 ◽  
Author(s):  
Eloisa Castillo-Saavedra ◽  
Juan José Castillo-Dávila ◽  
Dania Lizet Quintanilla-Flores ◽  
Anally Jamile Soto-García

Abstract Introduction: There is evidence that insulin resistance is associated with different types of cancer. This resistance increases the incidence of benign thyroid nodules and the risk of developing Differentiated Thyroid Cancer, however, studies in this regard are required. Objective: To assess if there are differences in the prevalence of insulin resistance in patients with differentiated thyroid cancer and patients with benign thyroid nodule. Material and methods: Prospective, analytical and cross-sectional design study. Patients undergoing thyroidectomy and definitive diagnosis of differentiated thyroid cancer or benign thyroid nodule were included. Anthropometric and biochemical variables were evaluated and differences in prevalence of insulin resistance were identified. To compare continuous variables, Student's T or Mann Whitney's U was used. To evaluate differences in categorical variables, the two-sided Fisher test when two binary variables were contrasted and Pearson's X2 in variables with more than two categories. Factors were analyzed through multivariate analysis obtaining odds ratio and 95% confidence interval.Results: A lower possibility of cancer was concluded: hereditary-family history of thyroid disease and hypothyroidism (OR 0.159; 95% CI 0.038-0.669; p = 0.012). Positive HOMA-IR showed a significant association in residual structural disease (P = 0.050) and local vascular invasion (p = 0.014).Conclusions: No significant association was obtained between positive HOMA-IR and Differentiated Thyroid Cancer, compared with the Benignity group. It seems that there is a greater tendency to lack of structural and biochemical resolution in patients with malignancy and positive HOMA-IR.


2020 ◽  
pp. 73-78
Author(s):  
Hung Nguyen Trung ◽  
Thuy Nguyen Hai ◽  
Quan Nguyen Phuoc Bao

Objectives: To compare the levels and pathological values of serum Tg and TgAb between the patients with benign and malignant thyroid nodules and evaluate the relationship between serum Tg and TgAb levels with the rim characteristic and elasticity score of the nodule by thyroid elasto-echography. Subjects: 30 patients with thyroid nodules, Serum Tg and TgAb levels and thyroid elasto-echography are examen before operation. Results: The ratio of the positive Tg level of malignant thyroid nodules was higher than the benign thyroid nodules (16.7% vs 8.3%) but the serum Tg level was not significantly different (33.48 ± 38.67 ng/ml vs 27.32 ± 28.44 ng/ml, p > 0.05) and The ratio of positive TgAb level of malignant thyroid nodules was higher than that of benign thyroid nodules (22.2% vs 0%) but serum TgAb level was not different (64.15 ± 14.91 UI/ml vs 16.9 ± 14.48 UI/ml, p > 0.05). The combination of the ratio of positive Tg and positive TgAb level did not show any difference in the ratio of pathological value between benign and malignant thyroid nodules (5.6% vs 0%). Serum Tg levels in patients with irregular rim thyroid nodules were higher than those in patients with regular rim thyroid nodules but the serum Tg level was not different when evaluated with the elastic score. Conclusions: The mean level and ratio of the pathological value of serum Tg and TgAb did not differ between malignant and benign thyroid nodules. There is a relationship between serum Tg level and irregular rim characteristic of thyroid nodule (p < 0.05). Key words: serum thyroglobulin level, serum anti thyroglobulin level, thyroid nodule.


2006 ◽  
Vol 24 (12) ◽  
pp. 1839-1845 ◽  
Author(s):  
Olaf Thuerigen ◽  
Andreas Schneeweiss ◽  
Grischa Toedt ◽  
Patrick Warnat ◽  
Meinhard Hahn ◽  
...  

Purpose Primary systemic therapy (PST) with gemcitabine (G), epirubicin (E), and docetaxel (Doc) has resulted in a pathologic complete response (pCR) in 26% of primary breast cancer patients. This study was aimed at the identification of a gene expression signature in diagnostic core biopsy tissue samples that predicts pCR. Patients and Methods Core biopsy samples from patients with operable primary breast cancer, T2-4N0-2M0, enrolled onto two phase I and II trials evaluating GEDoc (n = 48) and GE sequentially followed by Doc (GEsDoc; n = 52) as PST were snap frozen and subjected to RNA expression profiling. A signature predicting pCR was discovered in the training set (GEsDoc) applying a support vector machine algorithm, and performance of this classifier was validated on the independent test set (GEDoc) by receiver operator characteristics analysis. Results We identified a signature consisting of 512 genes, which was enriched in genes involved in transforming growth factor beta and RAS-mediated signaling pathways, that predicts pCR with a sensitivity of 78%, a specificity of 90%, and an overall accuracy of 88% (95% CI, 75% to 95%). Apart from our signature, only HER2 overexpression was an independent predictor of pCR in multivariate analysis. Conclusion In conclusion, our gene expression signature allows prediction of pCR to PST containing G, E, and Doc with unprecedented high overall accuracy and robustness.


2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Zhongjun Tang ◽  
Kebo Cai

Background. Uveal melanoma (UM) has favorable local tumor control, but once metastasis develops, the prognosis is rather poor. Thus, it is urgent to develop metastasis predicting markers. Objective. Our study investigated a novel gene expression-based signature in predicting metastasis for patients with UM. Methods. In the discovery phase, 63 patients with UM from GEO data set GSE22138 were analyzed using the Weighted Correlation Network Analysis (WGCNA) to identify metastasis-related hub genes. The Least Absolute Shrinkage and Selection Operator (Lasso) Cox regression was used to select candidate genes and build a gene expression signature. In the validation phase, the signature was validated in The Cancer Genome Atlas database. Results. Forty-one genes were identified as hub genes of metastasis by WGCNA. After the Lasso Cox regression analysis, eight genes including RPL10A, EIF1B, TIPARP, RPL15, SLC25A38, PHLDA1, TFDP2, and MEGF10 were highlighted as candidate predictors. The gene expression signature for UM (UMPS) could independently predict MFS by univariate and multivariate Cox regression analysis. Incorporating UMPS increased the AUC of the traditional clinical model. In the validation cohort, UMPS performed well in predicting the MFS of UM patients. Conclusions. UMPS, an eight-gene-based signature, is useful in predicting prognosis for patients with UM.


2019 ◽  
Vol 32 (8) ◽  
pp. 895-901 ◽  
Author(s):  
Juanita K. Hodax ◽  
Kimberly Bowerman ◽  
Jose Bernardo Quintos

Abstract Background The American Thyroid Association (ATA) recommendations for the follow-up of thyroid nodules with benign fine needle aspiration (FNA) cytology in children are largely based on adult data, despite well-characterized differences between thyroid nodules in adults and children. We aimed to determine the optimal time interval for repeat evaluation of an FNA-benign thyroid nodule in a pediatric patient. Methods This is a retrospective chart review of patients <19 years of age from 2003 to 2013 with a benign thyroid nodule by FNA cytology. Results We identified 43 patients with benign thyroid nodule cytology on FNA. The average age at diagnosis was 15.6 years, with female predominance (91%). Initial ultrasound (US) findings showed an average nodule size of 2.5 cm, 10% with calcifications, 37% hyperemia, 29% hypoechogenicity and 7% lymphadenopathy. Follow-up US was done in 42%. The first follow-up US occurred on average at 15 months after the initial US. Four patients had nodules with significant growth over time. One patient with papillary thyroid carcinoma (PTC) on final pathology initially had a decreasing nodule size, and then a subsequent increase in the nodule size after 4.5 years. Thyroid nodules were surgically removed in 33% with the final pathology showing a benign cytology in four patients, follicular adenoma in eight patients and PTC in two patients. Conclusions The majority of patients with benign thyroid nodules had no significant increase in nodule size in the first year of follow-up, including one patient who was subsequently found to have PTC. We recommend follow-up US at 1 year after initial presentation in low-risk pediatric patients with benign thyroid nodule cytology.


2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Cara Murphy ◽  
Ankur Gupta

Abstract Background: Elevated thyroglobulin levels are most commonly associated with differentiated thyroid carcinoma and these levels are often used to monitor for disease recurrence. Thyroglobulin antibody levels can be elevated in both Hashimoto’s Thyroiditis and Graves’ Disease and these antibodies can interfere with thyroglobulin levels as detailed by Spencer, Wang (1). With benign thyroid nodules, there is limited research regarding thyroglobulin levels as studied in Chinnappa, et al (2). Clinical Case: A 31-year woman presented with a palpable thyroid nodule and dysphagia. Her primary care physician ordered thyroid labs including normal TSH (1.3 mIU/L, n0.4-4 mIU/L), normal thyroid peroxidase antibody (56 units, n&lt;250units), normal thyroglobulin antibody level (&lt;1 IU/mL, n&lt;1 IU/mL), and elevated thyroglobulin level (469.1 ng/mL, n2.8-40.9 ng/mL). Her thyroglobulin levels remained elevated on repeat testing (224.4 ng/mL, n2.8-40.9) one month later. In addition, her thyroglobulin lab studies were repeated with HAMA treatment and remained elevated (277.7 ng/mL, n2.8-40.9). Office ultrasound showed longest dimension of nodule to be 5 cm and patient received FNA biopsy. Biopsy results were reported as a benign nodule and it was recommended to follow-up in 12 months. Six months later the patient reported having increasing dysphagia. She underwent Barium swallow which showed no abnormalities. She had a growth increase of 35% on repeat imaging along with increasing neck pressure and discomfort and was referred to an ENT for surgery. Final pathology after left thyroid and isthmus thyroidectomy was reported as “Multinodular hyperplasia with background thyroid parenchyma histologically unremarkable. Negative for malignancy.” Thyroglobulin levels subsequently returned to within the normal range and the patient’s dysphagia resolved. Conclusion: Thyroglobulin levels can be markedly elevated with benign thyroid nodules, which can mislead physicians and increase concern for thyroid cancer. References: (1) Spencer, CA, Wang, CC. Thyroglobulin measurement. Techniques, clinical benefits, and pitfalls. Endocrinol Metab Clin North Am. 1995 Dec; 24(4): 841-63. (2) Chinnappa, P, Taguba, L, Arciaga, R, Faiman, C, Siperstein, A, Mehta, AE, Reddy SK, Nasr, C, Gupta MK. Detection of thyrotropin-receptor messenger ribonucleic acid (mRNA) and thyroglobulin mRNA transcripts in peripheral blood of patients with thyroid disease: sensitive and specific markers for thyroid cancer. J Clin Endocrinol Metab. 2004 Aug;89(8):3705-9.


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