Delta-like ligand 4 level in colorectal cancer is associated with tumor aggressiveness and clinical outcome

Article type: Research Article

Authors: Zhang, Zixi^{a; b} | Li, Xiao^a | Yan, Xueli^a | Qiu, He^a | Li, Gai^a | Guo, Xiaowen^a | Lu, Yan^a | Yang, Jingyi^c | Jiao, Min^d | Chen, Xue^e | Zhu, Shaojun^f | Dang, Chengxue^g | Wang, Weizhong^h | Chu, Dake^{a; *}

Affiliations: [a] Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China | [b] Department of Dermatology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China | [c] Information Center, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China | [d] Department of Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China | [e] National Local Joint Engineering Research Center for Precision Surgery and Regenerative Medicine and Regenerative Medicine and Surgical Engineering Research Center of Shaanxi Province, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, China | [f] Department of Pathology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, Shaanxi, China | [g] Department of Surgical Oncology, | [h] Department of Gastrointestinal Surgery, Xijing Hospital of Digestive Diseases, The Fourth Military Medical University, Xi’an, Shaanxi, China

Correspondence: [*] Corresponding author: Dake Chu, Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi 710061, China. Tel.: +86 29 85323922; Fax: +86 29 85323922; E-mail: [email protected].

Abstract: BACKGROUND: The Notch signaling regulates numerous cell growth, differentiation, and death. However, the expression pattern of its ligand Delta-like 4 (DLL4) in tumors is still uncertain. OBJECTIVE: In the present study, we examined DLL4 expression in colorectal cancer as well as assessed its role as a prognostic indicator in the present study. METHODS: DLL4 expression was examined by immunohistochemistry in 289 surgically resected specimens of colorectal cancer and adjacent normal tissues. The relationship between DLL4 expression and clinicopathological characteristics was analyzed. The association of DLL4 expression with the patients’ overall survival rate was assessed by Kaplan-Meier and Cox proportional-hazards regression. RESULTS: Increased DLL4 level was detected in colorectal cancer compared with that of normal tissues. Elevated DLL4 level in colorectal cancer was associated with increased body mass index of patients. Moreover, increased DLL4 level was also found to be correlated with tumor invasion, metastases and unfavorable clinical outcom of patients. CONCLUSIONS: DLL4 level is increased in colorectal cancer, especially in patients with increased body mass index, indicating potential involvement of obesity-related tumorigenesis and development. It might also serve as a novel molecular marker to predicate outcome of patients.

Keywords: DLL4, colorectal cancer, immunohistochemistry, body mass index, prognosis

DOI: 10.3233/CBM-200986

Journal: Cancer Biomarkers, vol. 33, no. 3, pp. 415-422, 2022