Expression of serine/glycine metabolism-related proteins is different according to the thyroid cancer subtype
Open accessAbstract
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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PSPH is a promising prognostic biomarker in different cancers such as advanced colorectal cancer, thyroid cancer, and melanoma.
“PSPH is associated with the development of various cancers and is a promising prognostic biomarker in different cancers such as advanced colorectal cancer [17], thyroid cancer [18] and melanoma [19].”
From Phosphoserine phosphatase as a prognostic biomarker in patients with gastric cancer and its potential association with immune cells (2022) · cites this paper as [18]
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- Authors
- Sun, W. Y., Kim, H. M., Jung, W.-H., & Koo, J. S.
- Affiliations
- The Catholic University of Korea Daejeon St. Mary's Hospital (KR)
- Yonsei University (KR)
- Corresponding author
- Koo, Ja Seung
- Venue
- Journal of Translational Medicine
- Published
- 2016-06-08
- Volume
- 14
- Issue
- 1
- Pages
- 168-168
- ISSN
- 1479-5876 (ISSN-L)
- PMC
- PMC4898323
- OpenAlex
- W2414264867
- Cited by
- 77
- References
- 31
- Citations by year
- 2025: 11 · 2024: 8 · 2023: 15 · 2022: 9 · 2021: 11 · 2020: 3 · 2019: 7 · 2018: 8 · 2017: 3 · 2016: 2
- FWCI
- 7.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- Journal of Translational Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
- Funders
- National R&D Program for Cancer Control (1420080)
- Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (2015R1A1A1A05001209)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Health Sciences › Medicine › Otorhinolaryngology › Head and Neck Cancer Studies
- Keywords
- serine/glycine metabolism, thyroid cancer subtypes, papillary thyroid carcinoma, follicular thyroid carcinoma, medullary thyroid carcinoma, poorly differentiated thyroid carcinoma, anaplastic thyroid carcinoma, PHGDH, PSAT1, phosphoserine phosphatase, SHMT1, glycine decarboxylase, BRAF V600E mutation, prognostic factors
- MeSH terms
- Thyroid Cancer, Papillary, Carcinoma, Carcinoma, Papillary, Glutamine, Glycine, Humans, Mutation, Neoplasm Proteins, Prognosis, Serine, Thyroid Neoplasms, Disease-Free Survival
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