Stromal lactic acid transporter : MCT4 expression as an indicator of prognosis in papillary thyroid cancer
Year: 2018
Type: dissertation
Study design: Observational Study
Abstract: hexokinases (HK), glucose transporter (GLUT), lactic dehydrogenase (LDH), and pyruvate kinases (PK) was also investigated according to the status of MCT4 mRNA expression.Immunohistochemical (IHC) staining analyses of MCT1 and MCT4 were performed using human thyroid cancer tissue, and the expression status of these transporters were compared with clinicopathological characteristics.Results: MCT1 and MCT4 expression were remarkably increased in PTC compared to paired normal thyroid tissue in THCA, GSE33630, and my own RNA-sequence data.In addition, the expression of MCT4 mRNA in PTC showed strong positive correlations with HK3 (r=0.4911,P<0.0001), GLUT1 (r=0.2723,P=0.0002), LDHA (r=0.4813,P=0.0001), PKLR (r=0.0797,P=0.0028), and PKM2 (r=0.4895,P<0.0001).In the analyses of the clinicopathological parameters using THCA data, high MCT4 expression was correlated with BRAFV600E mutation, intermediate and high recurrence risk, advanced tumor (stage T3 and T4), lymph node stage (N1a and N1b), and the simultaneous presence of BRAFV600E mutation and TERT promoter mutation (P<0.0001).Supporting the results from the public repository, in this study, IHC staining indicated that high stromal MCT4 levels (grade 2) were specifically associated with aggressive tumor behavior including advanced tumor (stage T3 and T4), lymph node stage (N1a and N1b), and TNM stage (III and IV) (P<0.0001).However, the degree of epithelial MCT4 staining had no prognostic value.Conclusion: These findings indicate the pivotal role of MCT4 in PTC progression, and support the use of stromal MCT4 as a biomarker and potential therapeutic target in aggressive PTC. ---------------------------------------------------------------------------------------------Key words: thyroid cancer, MCT4, Warburg effect, lactate transporter * P values calculated by Student's t-test.Data are mean ± SD. † P values calculated by χ 2 test or linear-by-linear association. Others: columnar cell variant, diffuse sclerosing variant, cribriform-morular variant, etc. * P values calculated by Student's t-test.Data are mean ± SD. † P values calculated by χ 2 test or linear-by-linear association. Others: columnar cell variant, diffuse sclerosing variant, cribriform-morular variant, etc. * P values calculated by Student's t-test.Data are mean ± SD. † P values calculated by χ 2 test or linear-by-linear association.
Author: 임승혁
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2940737468