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. 2023 Nov 15;24(22):16334.
doi: 10.3390/ijms242216334.

Role of ST6GAL1 in Thyroid Cancers: Insights from Tissue Analysis and Genomic Datasets

Ivana Gunjača  1 , Benjamin Benzon  2 , Nikolina Pleić  1 , Mirjana Babić Leko  1 , Valdi Pešutić Pisac  3 , Ana Barić  4 , Dean Kaličanin  1 , Ante Punda  4 , Ozren Polašek  5 , Katarina Vukojević  2 , Tatijana Zemunik  1
Affiliations

Role of ST6GAL1 in Thyroid Cancers: Insights from Tissue Analysis and Genomic Datasets

Ivana Gunjača et al. Int J Mol Sci. .

Abstract

Thyroid cancer is the predominant endocrine-related malignancy. ST6 β-galactoside α2,6-sialyltransferase 1 (ST6GAL1) has been studied in various types of cancers; however, the expression and function of ST6GAL1 in thyroid cancer has not been investigated so far. Previously, we conducted two genome-wide association studies and have identified the association of the ST6GAL1 gene with plasma thyroglobulin (Tg) levels. Since Tg levels are altered in thyroid pathologies, in the current study, we wanted to evaluate the expression of ST6GAL1 in thyroid cancer tissues. We performed an immunohistochemical analysis using human thyroid tissue from 89 patients and analyzed ST6GAL1 protein expression in papillary thyroid cancer (including follicular variant and microcarcinoma) and follicular thyroid cancer in comparison to normal thyroid tissue. Additionally, ST6GAL1 mRNA levels from The Cancer Genome Atlas (TCGA, n = 572) and the Genotype-Tissue Expression (GTEx) project (n = 279) were examined. The immunohistochemical analysis revealed higher ST6GAL1 protein expression in all thyroid tumors compared to normal thyroid tissue. TCGA data revealed increased ST6GAL1 mRNA levels in both primary and metastatic tumors versus controls. Notably, the follicular variant of papillary thyroid cancer exhibited significantly higher ST6GAL1 mRNA levels than classic papillary thyroid cancer. High ST6GAL1 mRNA levels significantly correlated with lymph node metastasis status, clinical stage, and reduced survival rate. ST6GAL1 emerges as a potential cancer-associated glycosyltransferase in thyroid malignancies, offering valuable insights into its diagnostic and prognostic significance.

Keywords: ST6GAL1; follicular thyroid cancer; follicular variant of papillary thyroid carcinoma; microcarcinoma; papillary thyroid cancer.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Immunofluorescent staining in (A) follicular variant of papillary thyroid cancer (FVPTC); (B) papillary thyroid cancer (PTC); (C) follicular thyroid cancer (FTC); (D) microcarcinoma; (E) normal thyroid tissue (control); all are with ST6GAL1 (arrows) and their co-expression with DAPI nuclear staining. All images were taken with a magnification of 40×. (F) Fold increases of ST6GAL1 expression relative to the control (healthy tissue) group in different types of thyroid cancer and healthy thyroid tissue (the dotted line represents a fold increase of 1, i.e., no increase relative to the control group).
Figure 2
Figure 2
Fold increases in ST6GAL1 protein expression relative to the control (healthy tissue) group stratified by (A) clinical stage, (B) lymph node metastasis, and (C) invasion of blood or lymph vessels. The dotted line represents a fold increase of 1, i.e., no increase relative to the control group.
Figure 3
Figure 3
Survival analysis of the ST6GAL1 mRNA levels in thyroid carcinomas (TCGA cohort). Kaplan–Meier analysis and log-rank tests show the following: (A) no significant difference between the survival rates of participants with high ST6GAL1 mRNA levels (upper 25%) and low ST6GAL1 mRNA levels; (B) a significant correlation of high ST6GAL1 mRNA levels (upper 25%) with shorter overall survival in the subgroup of men (p = 0.0004).
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