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Lactate Dehydrogenase A as a Potential New Biomarker for Thyroid Cancer

Authors
 Eun Jeong Ban  ;  Daham Kim  ;  Jin Kyong Kim  ;  Sang-Wook Kang  ;  Jandee Lee  ;  Jong Ju Jeong  ;  Kee-Hyun Nam  ;  Woong Youn Chung  ;  Kunhong Kim 
Citation
 Endocrinology and Metabolism (대한내분비학회지), Vol.36(1) : 96-105, 2021-02 
Journal Title
 Endocrinology and Metabolism (대한내분비학회지) 
ISSN
 2093-596X 
Issue Date
2021-02
Keywords
BRAF ; Biomarkers ; Lactate dehydrogenase A ; Prognosis ; Thyroid cancer, papillary
Abstract
Background: Several cancers show increased levels of lactate dehydrogenase A (LDHA), which are associated with cancer progression. However, it remains unclear whether LDHA levels are associated with papillary thyroid cancer (PTC) aggressiveness or with the presence of the PTC prognostic marker, the BRAFV600E mutation. This study aimed to evaluate the potential of LDHA as a PTC prognostic marker. Methods: LDHA expression was examined in 83 PTC tissue specimens by immunohistochemistry. Human thyroid cell lines were genetically manipulated to overexpress BRAFV600E or were treated with a BRAF-specific short hairpin RNA (shBRAF), whose effects on LDHA expression were evaluated by Western blotting. Data from 465 PTC patients were obtained from The Cancer Genome Atlas (TCGA) database and analyzed to validate the in vitro results. Results: LDHA was aberrantly overexpressed in PTC. Intense immunostaining for LDHA was observed in PTC specimens carrying mutated BRAF, whereas the intensity was less in wild-type BRAF samples. Overexpression of BRAFV600E resulted in LDHA upregulation, whereas treatment with shBRAF downregulated LDHA in human thyroid cell lines. Furthermore, LDHA mRNA expression was significantly elevated and associated with BRAFV600E expression in thyroid cancer tissues from TCGA database. Additionally, LDHA overexpression was found to be correlated with aggressive clinical features of PTC, such as lymph node metastases and advanced tumor stages. Conclusion: LDHA overexpression is associated with the BRAFV600E mutation and an aggressive PTC behavior. Therefore, LDHA may serve as a biomarker and therapeutic target in PTC.
Files in This Item:
T202100782.pdf Download
DOI
10.3803/EnM.2020.819
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Sang Wook(강상욱) ORCID logo https://orcid.org/0000-0001-5355-833X
Kim, Kun Hong(김건홍) ORCID logo https://orcid.org/0000-0001-5639-6372
Kim, Daham(김다함) ORCID logo https://orcid.org/0000-0003-1871-686X
Kim, Jin Kyong(김진경)
Nam, Kee Hyun(남기현) ORCID logo https://orcid.org/0000-0002-6852-1190
Lee, Jan Dee(이잔디) ORCID logo https://orcid.org/0000-0003-4090-0049
Chung, Woong Youn(정웅윤)
Jeong, Jong Ju(정종주) ORCID logo https://orcid.org/0000-0002-4155-6035
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182236
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