Genetic Variants in the<i>ST6GAL1</i>Gene Are Associated with Thyroglobulin Plasma Level in Healthy Individuals

Matana, Antonela; Popović, Marijana; Boutin, Thibaud; Torlak, Vesela; Brdar, Dubravka; Gunjača, Ivana; Kolčić, Ivana; Perica, Vesna Boraska; Punda, Ante; Rudan, Igor; Polašek, Ozren; Barbalić, Maja; Hayward, Caroline; Zemunik, Tatijana

doi:10.1089/thy.2018.0661

Cited by 8 publications

(11 citation statements)

References 54 publications

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“…Tg is a secretory protein synthesized in the thyrocyte endoplasmic reticulum, and its functions are iodide storage and thyroid hormonogenesis (14,23). Tg is widely used for monitoring for DTC recurrence and diagnosis of lymphatic metastasis lymph node fine-needle aspiration biopsy (24,25). However, whether preoperative serum Tg could predict the malignancy or lymphatic metastasis of PTC is still controversial.…”

Section: Discussionmentioning

confidence: 99%

Preoperative serum thyroglobulin is a risk factor of skip metastasis in papillary thyroid carcinoma

Huang¹,

Song²,

Wang³

et al. 2020

Ann Transl Med

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Background: Lymph node metastasis of papillary thyroid carcinoma (PTC) was a significant risk factor of local recurrence and distant metastasis, and our study aimed to identify predictive factors of skip metastasis in PTC, helping surgeons to build a strategy when facing patients in N1b stage with clinical central lymph node-negative.Methods: A total of 304 patients who underwent total thyroidectomy with central and lateral lymph node dissection and were diagnosed PTC with lateral lymph node metastasis (LLNM) in the Department of General Surgery at Guangdong Provincial People's Hospital were enrolled. We collected clinicopathological characteristics and analyzed their correlation with skip metastasis by univariate and multivariate analysis. Results:The incidence of skip metastasis in PTC was 14.8%. Univariate analysis showed that age, tumor diameter, primary tumor location, and preoperative serum thyroglobulin (Tg) were risk factors. Age (P=0.049, OR =3.418), primary tumor location (P<0.001, OR =7.279), and Tg (P=0.038, OR =9.412) were independent predictors in PTC by multivariate analysis.Conclusions: Skip metastasis of PTC was significantly associated with preoperative serum Tg ≤77 ng/mL, tumor diameter ≤10 mm, age ≥55, and tumor located in the upper lobe. It is the first time to demonstrate that Tg is associated with skip metastasis of PTC.

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Section: Discussionmentioning

confidence: 99%

Preoperative serum thyroglobulin is a risk factor of skip metastasis in papillary thyroid carcinoma

Huang¹,

Song²,

Wang³

et al. 2020

Ann Transl Med

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“…TG is widely used for monitoring differentiated thyroid cancer recurrence and diagnosing LNM. [30,31] However, whether preoperative serum TG could predict CLNM in PTC is still controversial. Kim et al [32] discovered that a TG concentration > 63.4 ng/mL was useful in predicting CLNM (P < 0.05, OR = 9.412), while Patell et al [33] showed that there was no correlation between TG concentration and CLNM.…”

Section: Discussionmentioning

confidence: 99%

Application of Machine Learning to Predict Cervical Lymph Node Metastasis from Micropapillary Thyroid Carcinoma with Ultrasound

Shen¹,

Zhou²,

Xu³

et al. 2021

Preprint

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Background This study aims to determine the prediction performance of a machine learning-based clinical model for cervical lymph node metastasis (CLNM) in micropapillary thyroid carcinoma (MPTC) with ultrasound (US).Methods Patients with MPTC who underwent total or hemithyroidectomy with unilateral or bilateral prophylactic central neck dissection were included (n = 692). Nodal status was pathologically determined. Clinical and US features and thyroid function markers were extracted to build a random forest model. A nomogram with the significant predictive risk factors from multivariable logistic regression analysis was built to visualize hazard rates. Finally, the predictive performances of the models were compared.Results Overall, 332 patients (47.98%) had CLNM. In multiple logistic regression, the strong predictive risk factors for CLNM were younger age, larger anteroposterior diameter, lower anteroposterior/transverse diameter (A/T) ratio, and higher thyroglobulin (TG) concentration (P < 0.05). The random forest and nomogram models showed good predictive performance with the area under the curves (AUCs) of 0.836 and 0.780, respectively, which were significantly higher than those without A/T ratio in the models (AUCs: 0.807 vs. 0.722, all P < 0.05). The AUC of the A/T ratio as a single feature for predicting CLNM was 0.744, while A/T ratio (≤ 0.828) combined with anteroposterior diameter (≥ 10 mm) yielded a higher AUC of 0.754 for predicting CLNM.Conclusions The machine learning-based clinical model with US had a good predictive performance for CLNM in MPTC patients. This clinical model may facilitate surgical decision-making for MPTC, especially regarding whether cervical lymph node dissection is warranted.

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“…In our previous work [19], the top rs4012172 SNP was estimated to explain 3.19% of the variance in Tg levels. In the current study, we estimated the proportion of variance in phenotypes explained by all available genotypes (PVE) or the "chip heritability", as well as the proportion of genetic variance explained by variants with major effect (PGE).…”

Section: Snp Heritability Estimationmentioning

confidence: 99%

“…Our recent genome-wide association study (GWAS) showed an association of 16 variants within the ST6GAL1 gene with plasma Tg levels in healthy individuals [19]. This was the first GWAS to investigate genes associated with plasma Tg levels.…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Association Analysis and Genomic Prediction of Thyroglobulin Plasma Levels

Pleić

Leko

Gunjača

et al. 2022

IJMS

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Thyroglobulin (Tg) is an iodoglycoprotein produced by thyroid follicular cells which acts as an essential substrate for thyroid hormone synthesis. To date, only one genome-wide association study (GWAS) of plasma Tg levels has been performed by our research group. Utilizing recent advancements in computation and modeling, we apply a Bayesian approach to the probabilistic inference of the genetic architecture of Tg. We fitted a Bayesian sparse linear mixed model (BSLMM) and a frequentist linear mixed model (LMM) of 7,289,083 variants in 1096 healthy European-ancestry participants of the Croatian Biobank. Meta-analysis with two independent cohorts (total n = 2109) identified 83 genome-wide significant single nucleotide polymorphisms (SNPs) within the ST6GAL1 gene (p<5×10−8). BSLMM revealed additional association signals on chromosomes 1, 8, 10, and 14. For ST6GAL1 and the newly uncovered genes, we provide physiological and pathophysiological explanations of how their expression could be associated with variations in plasma Tg levels. We found that the SNP-heritability of Tg is 17% and that 52% of this variation is due to a small number of 16 variants that have a major effect on Tg levels. Our results suggest that the genetic architecture of plasma Tg is not polygenic, but influenced by a few genes with major effects.

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Genetic Variants in theST6GAL1Gene Are Associated with Thyroglobulin Plasma Level in Healthy Individuals

Cited by 8 publications

References 54 publications

Preoperative serum thyroglobulin is a risk factor of skip metastasis in papillary thyroid carcinoma

Preoperative serum thyroglobulin is a risk factor of skip metastasis in papillary thyroid carcinoma

Application of Machine Learning to Predict Cervical Lymph Node Metastasis from Micropapillary Thyroid Carcinoma with Ultrasound

Genome-Wide Association Analysis and Genomic Prediction of Thyroglobulin Plasma Levels

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