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Tumor Biology

, Volume 37, Issue 4, pp 5063–5074 | Cite as

DLL4 as a predictor of pelvic lymph node metastasis and a novel prognostic biomarker in patients with early-stage cervical cancer

  • Shanshan Yang
  • YunDuo Liu
  • BaiRong Xia
  • Jiangpeng Deng
  • TianBo Liu
  • Qi Li
  • YanPing Yang
  • YaoXian Wang
  • XiaoMing Ning
  • YunYan ZhangEmail author
  • Min XiaoEmail author
Original Article

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.

Keywords

Delta-like ligand 4 Cervical cancer Pelvic lymph node metastasis Prognosis 

Notes

Acknowledgments

The authors thank all the people and patients who had participated in this study. This work is supported by the Post Doctoral Fund of Heilongjiang Province (No. LBH-Z14171), the Health and Family Planning Commission of Heilongjiang Provincial (No. 2014-363), the National Natural Science Foundation of China (No. 81372786), and the HaiYan Foundation of Affiliated Tumor Hospital of Harbin Medical University (No. JJQN2014-07).

Compliance with ethical standards

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Shanshan Yang
    • 1
  • YunDuo Liu
    • 2
  • BaiRong Xia
    • 2
  • Jiangpeng Deng
    • 3
  • TianBo Liu
    • 2
  • Qi Li
    • 1
  • YanPing Yang
    • 1
  • YaoXian Wang
    • 1
  • XiaoMing Ning
    • 4
  • YunYan Zhang
    • 1
    Email author
  • Min Xiao
    • 5
    Email author
  1. 1.Department of Gynecological RadiotherapyThe Affiliated Tumor Hospital of Harbin Medical UniversityHarbinChina
  2. 2.Department of GynecologyThe Affiliated Tumor Hospital of Harbin Medical UniversityHarbinChina
  3. 3.Department of OncologyDazhou Central Hospital of Sichuan ProvinceDazhouChina
  4. 4.Department of PathologyThe Affiliated Tumor Hospital of Harbin Medical UniversityHarbinChina
  5. 5.Department of Breast SurgeryThe Affiliated Tumor Hospital of Harbin Medical UniversityHarbinChina

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