Relationships of BRAF mutation and HMGB1 to papillary thyroid carcinoma.
A poor papillary thyroid cancer (PTC) prognosis is strongly associated with the BRAF V600E mutation. During tumor progression, levels of the high mobility group box 1 (HMGB1) protein are often dysregulated. Results herein demonstrate that HMGB1 protein levels differ between tumor and adjacent non-tumor tissue and that HMGB1 mRNA levels were higher in wild-type BRAF PTC tissues than in BRAF V600E PTC tissues (2-△Ct 0.31 ± 0.25 vs. 0.16 ± 0.12; P < 0.05). HMGB1 protein levels also differed in the same manner (wild-type BRAF PTC tissues 0.11 ± 0.04 vs. BRAF V600E PTC tissues 0.03 ± 0.03; P < 0.001). Although not detected in peripheral blood, low levels of HMGB1 were significantly related to PTC cell lymph node metastasis and extra-glandular infiltration (P = 0.045 and P = 0.002). Experimental results at the cellular level were consistent with tissues and further verified the relationship of BRAF V600E and HMGB1. These findings demonstrate that the BRAF V600E mutation down-regulates levels of HMGB1, likely through activation of the mitogen-activated protein kinase (MAPK) signaling pathways.
Department of Endocrinology and Metabolism, Affiliated Hospital of Qingdao University, Qingdao 266555, China.
Xiaolei
X
Guan
Department of Endocrinology and Metabolism, Affiliated Hospital of Qingdao University, Qingdao 266555, China.
Ping
P
Wang
Qingdao Key Lab of Thyroid Disease, Affiliated Hospital of Qingdao University, Qingdao 266555, China.
Jingwei
J
Chi
Department of Endocrinology and Metabolism, Affiliated Hospital of Qingdao University, Qingdao 266555, China.
Shihua
S
Zhao
Department of Endocrinology and Metabolism, Affiliated Hospital of Qingdao University, Qingdao 266555, China. Electronic address: wf18661802019@163.com.
Fei
F
Wang
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000453:epidemiology* / Q000235:genetics*; D002291:Carcinoma, Papillary; D045744:Cell Line, Tumor; D002681:China / Q000453:epidemiology; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D024243:HMGB1 Protein / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D015203:Reproducibility of Results; D012307:Risk Factors; D012680:Sensitivity and Specificity; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000453:epidemiology* / Q000235:genetics*
D014408:Biomarkers, Tumor; D005819:Genetic Markers; D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
BRAF V600E; HMGB1; Papillary thyroid cancer