title: Prognostic values of DLK1 for surgery and imatinib mesylate adjuvant therapy in gastrointestinal stromal tumors.
abstract: The Delta-like 1 homolog (DLK1) gene is a paternal imprinting gene located on human chromosome 14q32, a site associated with frequent chromosomal mutations in GIST. The expression level of DLK1 is closely associated with the outcome of tumours. However, no study has reported the DLK1 expression in GIST. Here, we demonstrated that DLK1 showed low expression in GIST patients with low risk according to the modified National Institute of Health (NIH) criteria. With increasing tumour risk level, DLK1 gene and protein expression levels gradually increased. In the test cohort, tissue microarray data showed that DLK1 protein expression was significantly associated with tumour size, mitotic figure count, NIH risk level, and Ki67 expression. In terms of either disease-free survival (DFS) or overall survival (OS), the long-term outcome was significantly better in DLK1-negative patients than in DLK1-positive patients. Univariate and multivariate analyses suggested that DLK1 expression was an independent risk factor influencing tumour DFS. Additionally, for intermediate/high-risk GIST patients received postoperative IM adjuvant therapy, Kaplan-Meier analysis showed that IM adjuvant therapy was associated with a better outcome in DLK1-negative patients than in DLK1-positive patients. All of the above results were verified in the validation cohort. Taken together, DLK1 is a promising prognostic biomarker for GISTs that may help to predict surgical outcomes and guide adjuvant IM therapy.
authors.affiliation: Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200127, P. R. China.
authors.forename: Jia
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200127, P. R. China.
authors.forename: Ming
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200127, P. R. China.
authors.forename: Zizhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200127, P. R. China.
authors.forename: Wenyi
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200127, P. R. China.
authors.forename: Chaojie
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200127, P. R. China.
authors.forename: Lin
authors.initials: L
authors.lastname: Tu
authors.affiliation: Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghai 200127, P. R. China; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghai 200240, P. R. China.
authors.forename: Yeqian
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200127, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cao
keywords: DLK1; GIST; imatinib mesylate