title: A meta-analysis of prognostic roles of molecular markers in papillary thyroid carcinoma.
abstract: The prognostic role of molecular markers in papillary thyroid carcinoma (PTC) is a matter of ongoing debate. The aim of our study is to investigate the impact ofRAS,BRAF,TERTpromoter mutations andRET/PTCrearrangements on the prognosis of PTC patients. We performed a search in four electronic databases: PubMed, Scopus, Web of Science and Virtual Health Library (VHL). Data of hazard ratio (HR) and its 95% confidence interval (CI) for disease-specific survival (DSS) and disease-free survival (DFS) were directly obtained from original papers or indirectly estimated from Kaplan-Meier curve (KMC). Pooled HRs were calculated using random-effect model weighted by inverse variance method. Publication bias was assessed by using Egger's regression test and visual inspection of funnel plots. From 2630 studies, we finally included 35 studies with 17,732 patients for meta-analyses.TERTpromoter mutation was significantly associated with unfavorable DSS (HR = 7.64; 95% CI = 4.00-14.61) and DFS (HR = 2.98; 95% CI = 2.27-3.92).BRAFmutations significantly increased the risk for recurrence (HR = 1.63; 95% CI = 1.27-2.10) but not for cancer mortality (HR = 1.41; 95% CI = 0.90-2.23). In subgroup analyses,BRAFmutation only showed its prognostic value in short-/medium-term follow-up. Data regardingRASmutations andRET/PTCfusions were insufficient for meta-analyses.TERTpromoter mutation can be used as an independent and reliable marker for risk stratification and predicting patient's outcomes. The use ofBRAFmutation to assess patient prognosis should be carefully considered.
authors.affiliation: Department of PathologyCho Ray Hospital, Ho Chi Minh City, Vietnam huyvuong@hotmail.com.
authors.forename: Huy Gia
authors.initials: HG
authors.lastname: Vuong
authors.affiliation: Pham Ngoc Thach University of MedicineHo Chi Minh City, Vietnam.
authors.forename: Uyen N P
authors.initials: UN
authors.lastname: Duong
authors.affiliation: Faculty of MedicineUniversity of Jordan, Amman, Jordan.
authors.forename: Ahmed M A
authors.initials: AM
authors.lastname: Altibi
authors.affiliation: Department of PathologyUniversity of Medicine and Pharmacy, Ho Chi Minh City, Vietnam.
authors.forename: Hanh T T
authors.initials: HT
authors.lastname: Ngo
authors.affiliation: Department of PathologyCho Ray Hospital, Ho Chi Minh City, Vietnam.
authors.forename: Thong Quang
authors.initials: TQ
authors.lastname: Pham
authors.affiliation: Faculty of MedicineUniversity of Medicine and Pharmacy, Ho Chi Minh City, Vietnam.
authors.forename: Hung Minh
authors.initials: HM
authors.lastname: Tran
authors.affiliation: Laboratory of Translational ResearchArcispedale S. Maria Nuova-IRCCS, Reggio Emilia, Italy.
authors.forename: Greta
authors.initials: G
authors.lastname: Gandolfi
authors.affiliation: Department of PathologyUniversity of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
authors.forename: Lewis
authors.initials: L
authors.lastname: Hassell
keywords: BRAF; RAS; RET/PTC; TERT promoter; disease-free survival; disease-specific survival; genetic alteration; mutation; outcome; rearrangement; recurrence; relapse; survival