title: DLL4 as a predictor of pelvic lymph node metastasis and a novel prognostic biomarker in patients with early-stage cervical cancer.
abstract: Delta-like ligand 4 (DLL4), one of the five Notch signaling ligands in mammals, has an important function in proliferation, invasion, metastasis, progression, and angiogenesis of malignancies. This study aimed to investigate DLL4 expression level in early-stage cervical carcinoma and to evaluate its clinical significance. We used fresh frozen and paraffin-embedded cervical cancer tissues to analyze DLL4 expression and its clinical significance. DLL4 expression at both mRNA and protein levels in cervical cancer tissues was significantly higher than that in normal cervical tissues. High DLL4 protein level was clearly correlated with high International Federation of Gynecology and Obstetrics (FIGO) stage (P = 0.044), lymphovascular space involvement (LVSI) (P = 0.015), pelvic lymph node metastasis (PLNM) (P = 0.001), and recurrence (P < 0.001). Univariate and multivariate logistic regression analyses demonstrated that DLL4 overexpression was strongly associated with lymph node metastasis (odds ratio, 2.790; 95 % CI, 1.344-5.791; P = 0.006). Moreover, survival analysis revealed that DLL4 expression was an independent factor of unfavorable overall survival (hazard ratio, 2.130; 95 % CI, 1.108-4.097; P = 0.023) and disease-free survival (hazard ratio, 1.965; 95 % CI, 1.085-3.560; P = 0.026) in patients with cervical cancer. Overall, our data indicate that high DLL4 expression predicts pelvic lymph node metastasis and poor survival in cervical cancer. Therefore, DLL4 may be a potential clinical diagnostic marker for patients with early-stage cervical cancer.
authors.affiliation: Department of Gynecological Radiotherapy, The Affiliated Tumor Hospital of Harbin Medical University, Baojian Road 6, Nangang District, Harbin, 150081, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Yang
authors.affiliation: Department of Gynecology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: YunDuo
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Gynecology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: BaiRong
authors.initials: B
authors.lastname: Xia
authors.affiliation: Department of Oncology, Dazhou Central Hospital of Sichuan Province, Dazhou, China.
authors.forename: Jiangpeng
authors.initials: J
authors.lastname: Deng
authors.affiliation: Department of Gynecology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: TianBo
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Gynecological Radiotherapy, The Affiliated Tumor Hospital of Harbin Medical University, Baojian Road 6, Nangang District, Harbin, 150081, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Gynecological Radiotherapy, The Affiliated Tumor Hospital of Harbin Medical University, Baojian Road 6, Nangang District, Harbin, 150081, China.
authors.forename: YanPing
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Gynecological Radiotherapy, The Affiliated Tumor Hospital of Harbin Medical University, Baojian Road 6, Nangang District, Harbin, 150081, China.
authors.forename: YaoXian
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China.
authors.forename: XiaoMing
authors.initials: X
authors.lastname: Ning
authors.affiliation: Department of Gynecological Radiotherapy, The Affiliated Tumor Hospital of Harbin Medical University, Baojian Road 6, Nangang District, Harbin, 150081, China. zhangyunyan_1972@163.com.
authors.forename: YunYan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Breast Surgery, The Affiliated Tumor Hospital of Harbin Medical University, Harbin, China. doctor_xm@126.com.
authors.forename: Min
authors.initials: M
authors.lastname: Xiao
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D002135:Calcium-Binding Proteins; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics; D008197:Lymph Node Excision; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000473:pathology; D009367:Neoplasm Staging; D010386:Pelvic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000556:secondary / Q000601:surgery; D011379:Prognosis; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; D036341:Intercellular Signaling Peptides and Proteins
keywords: Cervical cancer; Delta-like ligand 4; Pelvic lymph node metastasis; Prognosis