Department of Emergency Surgery, Inner Mongolia Peoples' Hospital, Hohhot, Inner Mongolia, China (mainland).
Department of General Surgery, ZhuJiang Hospital of Southern Medical University, Guangzhou, Guangdong, China (mainland).
Med Sci Monit. 2018 Sep 26;24:6795-6808. doi: 10.12659/MSM.909205.
BACKGROUND The aim of this study was to investigate the expression of the BRAF V600E gene mutation and the RET/PTC gene rearrangement in the progression of papillary thyroid carcinoma (PTC) in 50 patients from Inner Mongolia. MATERIAL AND METHODS Clinical data, blood, and tissue samples were obtained from 50 patients with PTC and ten patients with benign thyroid adenoma. Expression of BRAF V600E, RET/PTC, nuclear factor-κB (NF-κB), interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, transforming growth factor (TGF)-β, C-X-C motif chemokine ligand (CXCL)1, CXCL2, C-C motif chemokine ligand (CCL)2, and CCL3 were measured using polymerase chain reaction (PCR), immunohistochemistry, and an enzyme-linked immunosorbent assay (ELISA). RESULTS Of the 50 patients with PTC, 37 patients expressed the BRAF V600E gene mutation, eight patients expressed RET/PTC, and five patients showed concomitant BRAF V600E and RET/PTC. Time to recurrence for patients with PTC with BRAF V600E was significantly increased compared with patients with concomitant BRAF V600E mutation and RET/PTC rearrangement (P<0.05). Expression of BRAF V600E, RET/PTC, and concomitant expression of BRAF V600E and RET/PTC were significantly associated with patient age and lymph node metastasis (P<0.05). Serum levels of NF-κB, IL-1β, IL-6, TNF-α, TGF-β and CCL3, and tumor tissue levels of IL-1β, IL-6, TNF-α, TGF-β, CXCL2 and CCL2 in patients with PTC were significantly increased compared with patients with benign thyroid adenoma, before and after surgery (P<0.05). CONCLUSIONS Expression of the BRAF V600E mutation and RET/PTC translocation promoted the activity of NF-κB, expression of inflammatory mediators, and lymph node metastases in patients with PTC.
本研究旨在探讨 50 例内蒙古地区甲状腺乳头状癌(PTC)患者中 BRAF V600E 基因突变和 RET/PTC 基因重排的表达情况。
收集 50 例 PTC 患者和 10 例甲状腺良性腺瘤患者的临床资料、血液和组织样本。采用聚合酶链反应(PCR)、免疫组织化学和酶联免疫吸附试验(ELISA)检测 BRAF V600E、RET/PTC、核因子-κB(NF-κB)、白细胞介素(IL)-1β、IL-6、肿瘤坏死因子(TNF)-α、转化生长因子(TGF)-β、C-X-C 基序趋化因子配体(CXCL)1、CXCL2、C-C 基序趋化因子配体(CCL)2 和 CCL3 的表达。
50 例 PTC 患者中,37 例表达 BRAF V600E 基因突变,8 例表达 RET/PTC,5 例同时表达 BRAF V600E 和 RET/PTC。与同时存在 BRAF V600E 突变和 RET/PTC 重排的患者相比,PTC 患者中 BRAF V600E 表达的患者复发时间明显延长(P<0.05)。BRAF V600E、RET/PTC 的表达以及 BRAF V600E 和 RET/PTC 的同时表达与患者年龄和淋巴结转移显著相关(P<0.05)。与甲状腺良性腺瘤患者相比,PTC 患者血清 NF-κB、IL-1β、IL-6、TNF-α、TGF-β 和 CCL3 水平以及肿瘤组织中 IL-1β、IL-6、TNF-α、TGF-β、CXCL2 和 CCL2 水平均显著升高,手术前后差异均有统计学意义(P<0.05)。
BRAF V600E 突变和 RET/PTC 易位的表达促进了 PTC 患者 NF-κB 的活性、炎症介质的表达和淋巴结转移。