Expression of serine/glycine metabolism-related proteins is different according to the thyroid cancer subtype

Woo Young Sun, Hye Min Kim, Woo Hee Jung, JaSeung Koo

Research output: Contribution to journalArticle

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Abstract

Background: The aim of this study was to investigate the expression and clinical implications of proteins related to serine/glycine metabolism in different subtypes of thyroid cancer. Methods: Tissue microarray (TMA) was constructed with tissues from 557 thyroid cancers, consisting of 244 papillary thyroid carcinomas (PTC), 112 follicular carcinomas (FC), 70 medullary carcinomas (MC), 23 poorly differentiated carcinomas (PDC), and 8 anaplastic carcinomas (AC). Immunohistochemical staining of the serine/glycine metabolism-related molecules phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase, (PSAT), phosphoserine phosphatase (PSPH), serine hydromethyl transferase (SHMT), and glycine decarboxylase (GLDC) was performed with the TMA blocks and the results were analyzed together with clinicopathologic parameters. Results: The expression of serine/glycine metabolism-related proteins differed among thyroid cancer subtypes. The expression rate of PHGDH (p<0.001), PSAT1 (p=0.001), PSPH (p=0.008), and tumoral SHMT1 (p<0.001) was higher in PDC and PTC (78.3, 21.7, 21.7, 30.4 and 63.4, 18.6, 12.8, 31.4%, respectively), and lowest in MC (15.7, 1.4, 0.0, 10.0%). Stromal SHMT1 expression was highest in AC (62.5%) and absent in all FC (p<0.001). In PTC, positivity for PSPH (p=0.041), tumoral SHMT1 (p=0.018), and stromal SHMT1 (p<0.001) expression was higher in the conventional type compared to follicular type (14.1 versus 2.5%, 33.6 versus 15.0%, 42.1 versus 10.0%, respectively). BRAF V600E mutation was associated with a higher rate of PHGDH (p<0.001), PSAT1 (p=0.001), PSPH (p<0.001), tumoral SHMT1 (p=0.001), stromal SHMT1 (p<0.001), and GLDC (p<0.001) expression compared to non-mutant cases (73.5 versus 40.6%, 23.1 versus 8.5%, 17.6 versus 1.9%, 37.0 versus 18.9%, 45.8 versus 21.7%, 21.8 versus 6.6%, respectively). In univariate analysis, stromal SHMT1 expression was associated with shorter disease-free survival (p=0.015) in follicular variant PTC, and GLDC positivity was associated with shorter overall survival (OS) in sclerotic stromal type (p=0.002). In FC, minimally invasive type, PSPH positivity correlated with shorter OS (p=0.045) and in MC, PHGDH positivity correlated with shorter OS (p=0.034). Conclusion: The expression of serine/glycine metabolism-related proteins differs among different thyroid cancer types, with a higher rate of expression in PDC and PTC, and lower rate of expression in MC. In PTC, the rate of expression is lower in the follicular variant and higher in cases with BRAF V600E mutation.

Original languageEnglish
Article number168
JournalJournal of Translational Medicine
Volume14
Issue number1
DOIs
Publication statusPublished - 2016 Jun 8

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Phosphoglycerate Dehydrogenase
Glycine Dehydrogenase (Decarboxylating)
Thyroid Neoplasms
Metabolism
Glycine
Serine
Carcinoma
Medullary Carcinoma
phosphoserine aminotransferase
Tissue
Microarrays
Proteins
Transferases
Mutation
phosphoserine phosphatase
Molecules
Disease-Free Survival
Papillary Thyroid cancer
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

@article{966dd2dedc3c4ad6990f1181b02c619b,
title = "Expression of serine/glycine metabolism-related proteins is different according to the thyroid cancer subtype",
abstract = "Background: The aim of this study was to investigate the expression and clinical implications of proteins related to serine/glycine metabolism in different subtypes of thyroid cancer. Methods: Tissue microarray (TMA) was constructed with tissues from 557 thyroid cancers, consisting of 244 papillary thyroid carcinomas (PTC), 112 follicular carcinomas (FC), 70 medullary carcinomas (MC), 23 poorly differentiated carcinomas (PDC), and 8 anaplastic carcinomas (AC). Immunohistochemical staining of the serine/glycine metabolism-related molecules phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase, (PSAT), phosphoserine phosphatase (PSPH), serine hydromethyl transferase (SHMT), and glycine decarboxylase (GLDC) was performed with the TMA blocks and the results were analyzed together with clinicopathologic parameters. Results: The expression of serine/glycine metabolism-related proteins differed among thyroid cancer subtypes. The expression rate of PHGDH (p<0.001), PSAT1 (p=0.001), PSPH (p=0.008), and tumoral SHMT1 (p<0.001) was higher in PDC and PTC (78.3, 21.7, 21.7, 30.4 and 63.4, 18.6, 12.8, 31.4{\%}, respectively), and lowest in MC (15.7, 1.4, 0.0, 10.0{\%}). Stromal SHMT1 expression was highest in AC (62.5{\%}) and absent in all FC (p<0.001). In PTC, positivity for PSPH (p=0.041), tumoral SHMT1 (p=0.018), and stromal SHMT1 (p<0.001) expression was higher in the conventional type compared to follicular type (14.1 versus 2.5{\%}, 33.6 versus 15.0{\%}, 42.1 versus 10.0{\%}, respectively). BRAF V600E mutation was associated with a higher rate of PHGDH (p<0.001), PSAT1 (p=0.001), PSPH (p<0.001), tumoral SHMT1 (p=0.001), stromal SHMT1 (p<0.001), and GLDC (p<0.001) expression compared to non-mutant cases (73.5 versus 40.6{\%}, 23.1 versus 8.5{\%}, 17.6 versus 1.9{\%}, 37.0 versus 18.9{\%}, 45.8 versus 21.7{\%}, 21.8 versus 6.6{\%}, respectively). In univariate analysis, stromal SHMT1 expression was associated with shorter disease-free survival (p=0.015) in follicular variant PTC, and GLDC positivity was associated with shorter overall survival (OS) in sclerotic stromal type (p=0.002). In FC, minimally invasive type, PSPH positivity correlated with shorter OS (p=0.045) and in MC, PHGDH positivity correlated with shorter OS (p=0.034). Conclusion: The expression of serine/glycine metabolism-related proteins differs among different thyroid cancer types, with a higher rate of expression in PDC and PTC, and lower rate of expression in MC. In PTC, the rate of expression is lower in the follicular variant and higher in cases with BRAF V600E mutation.",
author = "Sun, {Woo Young} and Kim, {Hye Min} and Jung, {Woo Hee} and JaSeung Koo",
year = "2016",
month = "6",
day = "8",
doi = "10.1186/s12967-016-0915-8",
language = "English",
volume = "14",
journal = "Journal of Translational Medicine",
issn = "1479-5876",
publisher = "BioMed Central",
number = "1",

}

Expression of serine/glycine metabolism-related proteins is different according to the thyroid cancer subtype. / Sun, Woo Young; Kim, Hye Min; Jung, Woo Hee; Koo, JaSeung.

In: Journal of Translational Medicine, Vol. 14, No. 1, 168, 08.06.2016.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Expression of serine/glycine metabolism-related proteins is different according to the thyroid cancer subtype

AU - Sun, Woo Young

AU - Kim, Hye Min

AU - Jung, Woo Hee

AU - Koo, JaSeung

PY - 2016/6/8

Y1 - 2016/6/8

N2 - Background: The aim of this study was to investigate the expression and clinical implications of proteins related to serine/glycine metabolism in different subtypes of thyroid cancer. Methods: Tissue microarray (TMA) was constructed with tissues from 557 thyroid cancers, consisting of 244 papillary thyroid carcinomas (PTC), 112 follicular carcinomas (FC), 70 medullary carcinomas (MC), 23 poorly differentiated carcinomas (PDC), and 8 anaplastic carcinomas (AC). Immunohistochemical staining of the serine/glycine metabolism-related molecules phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase, (PSAT), phosphoserine phosphatase (PSPH), serine hydromethyl transferase (SHMT), and glycine decarboxylase (GLDC) was performed with the TMA blocks and the results were analyzed together with clinicopathologic parameters. Results: The expression of serine/glycine metabolism-related proteins differed among thyroid cancer subtypes. The expression rate of PHGDH (p<0.001), PSAT1 (p=0.001), PSPH (p=0.008), and tumoral SHMT1 (p<0.001) was higher in PDC and PTC (78.3, 21.7, 21.7, 30.4 and 63.4, 18.6, 12.8, 31.4%, respectively), and lowest in MC (15.7, 1.4, 0.0, 10.0%). Stromal SHMT1 expression was highest in AC (62.5%) and absent in all FC (p<0.001). In PTC, positivity for PSPH (p=0.041), tumoral SHMT1 (p=0.018), and stromal SHMT1 (p<0.001) expression was higher in the conventional type compared to follicular type (14.1 versus 2.5%, 33.6 versus 15.0%, 42.1 versus 10.0%, respectively). BRAF V600E mutation was associated with a higher rate of PHGDH (p<0.001), PSAT1 (p=0.001), PSPH (p<0.001), tumoral SHMT1 (p=0.001), stromal SHMT1 (p<0.001), and GLDC (p<0.001) expression compared to non-mutant cases (73.5 versus 40.6%, 23.1 versus 8.5%, 17.6 versus 1.9%, 37.0 versus 18.9%, 45.8 versus 21.7%, 21.8 versus 6.6%, respectively). In univariate analysis, stromal SHMT1 expression was associated with shorter disease-free survival (p=0.015) in follicular variant PTC, and GLDC positivity was associated with shorter overall survival (OS) in sclerotic stromal type (p=0.002). In FC, minimally invasive type, PSPH positivity correlated with shorter OS (p=0.045) and in MC, PHGDH positivity correlated with shorter OS (p=0.034). Conclusion: The expression of serine/glycine metabolism-related proteins differs among different thyroid cancer types, with a higher rate of expression in PDC and PTC, and lower rate of expression in MC. In PTC, the rate of expression is lower in the follicular variant and higher in cases with BRAF V600E mutation.

AB - Background: The aim of this study was to investigate the expression and clinical implications of proteins related to serine/glycine metabolism in different subtypes of thyroid cancer. Methods: Tissue microarray (TMA) was constructed with tissues from 557 thyroid cancers, consisting of 244 papillary thyroid carcinomas (PTC), 112 follicular carcinomas (FC), 70 medullary carcinomas (MC), 23 poorly differentiated carcinomas (PDC), and 8 anaplastic carcinomas (AC). Immunohistochemical staining of the serine/glycine metabolism-related molecules phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase, (PSAT), phosphoserine phosphatase (PSPH), serine hydromethyl transferase (SHMT), and glycine decarboxylase (GLDC) was performed with the TMA blocks and the results were analyzed together with clinicopathologic parameters. Results: The expression of serine/glycine metabolism-related proteins differed among thyroid cancer subtypes. The expression rate of PHGDH (p<0.001), PSAT1 (p=0.001), PSPH (p=0.008), and tumoral SHMT1 (p<0.001) was higher in PDC and PTC (78.3, 21.7, 21.7, 30.4 and 63.4, 18.6, 12.8, 31.4%, respectively), and lowest in MC (15.7, 1.4, 0.0, 10.0%). Stromal SHMT1 expression was highest in AC (62.5%) and absent in all FC (p<0.001). In PTC, positivity for PSPH (p=0.041), tumoral SHMT1 (p=0.018), and stromal SHMT1 (p<0.001) expression was higher in the conventional type compared to follicular type (14.1 versus 2.5%, 33.6 versus 15.0%, 42.1 versus 10.0%, respectively). BRAF V600E mutation was associated with a higher rate of PHGDH (p<0.001), PSAT1 (p=0.001), PSPH (p<0.001), tumoral SHMT1 (p=0.001), stromal SHMT1 (p<0.001), and GLDC (p<0.001) expression compared to non-mutant cases (73.5 versus 40.6%, 23.1 versus 8.5%, 17.6 versus 1.9%, 37.0 versus 18.9%, 45.8 versus 21.7%, 21.8 versus 6.6%, respectively). In univariate analysis, stromal SHMT1 expression was associated with shorter disease-free survival (p=0.015) in follicular variant PTC, and GLDC positivity was associated with shorter overall survival (OS) in sclerotic stromal type (p=0.002). In FC, minimally invasive type, PSPH positivity correlated with shorter OS (p=0.045) and in MC, PHGDH positivity correlated with shorter OS (p=0.034). Conclusion: The expression of serine/glycine metabolism-related proteins differs among different thyroid cancer types, with a higher rate of expression in PDC and PTC, and lower rate of expression in MC. In PTC, the rate of expression is lower in the follicular variant and higher in cases with BRAF V600E mutation.

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