A meta-analysis evaluating the relationship between B-type Raf kinase mutation and cervical lymphatic metastasis in papillary thyroid cancer.

Abstract

Background:B-type Raf kinase (BRAF) mutation is proved to be a critical predictive factor in papillary thyroid cancer (PTC) with aggressive characteristics. However, the association between BRAF mutation and cervical lymphatic metastasis in PTC is controversial.Methods:We searched papers on the study of BRAF mutation and cervical lymphatic metastasis in PTC patients through PubMed, Web of Science, Embase, and Cochranelibrary. The BRAF (+) cases, BRAF (–) cases, and cervical lymphphatic metastatic cases in both BRAF (+) and BRAF (–) groups were collected. After Quality assessment, statistical Analysis (funnel plot and Harbord evaluation, Random-effect model, heterogeneity, subgroup analysis, sensitivity analysis, and metacum analysis) were done by the Review Manager (RevMan) 5.3 and stata14 statistical software.Results:There were 78 cross-section studies which met our inclusion criteria. And all of them had no selection bias, publication bias, or any other bias. A significant association existed between BRAF mutation and cervical lymph node metastasis (LNM) (odds ratio [OR] = 1.63; 95% confidence interval [CI]: 1.44–1.84; P < .05). Overall, 46 studies were conducted among East Asians. Twenty four articles had provided the data of central lymph node metastasis (CLNM), 11 articles with the data of lateral lymph node metastasis (LLNM), and classic/conventional PTC (CPTC) was analyzed in 10 studies. Subgroup analyses were performed based on ethnicity, metastatic site, and subtype of PTC. Significant association between BRAF (+) mutation and cervical LNM were indicated in East Asians (OR = 1.73; 95% CI: 1.49–2.02; P < .05), in non-East Asians (OR = 1.57; 95% CI: 1.26–1.96; P < .05), and in CLNM (OR = 1.80; 95% CI: 1.56–2.07; P < .05). While no significant association was found in LLNM (OR = 1.37; 95% CI: 0.76–2.48; P = .29 > .05) and in CPTC (OR = 1.32; 95% CI: 0.97–1.80; P = .08 > .05). We did not find any other major changes when sensitivity analysis was performed. The metacum analysis showed no significant association existed before 2012. While a significant association began to exist between BRAF mutation and LNM from 2012, and this association became stable from 2017.Conclusions:We consider that a significant association exists between BRAF mutation and cervical LNM. Further meta-analysis on subgroup may reveal some valuable factors between BRAF gene mutation and LNM. And we do not recommend that BRAF (+) as the biomarker for LNM in PTC.