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

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 265 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.

Protein cargo in extracellular vesicles as the key mediator in the progression of cancer

“…For example, delta-like 4 protein (DLL4) increases vessel branching and promotes cancer-associated modifications of the TME [ 105 ]. DLL4 was associated with tumour aggressiveness and an unfavourable clinical outcome in colorectal cancer patients [ 106 ]. Integrins are a family of proteins that direct exosomes to specific tissues, thus being partly responsible for premetastatic niche formation and metastatic tropism during breast cancer development [ 107 ].…”

Novel specific anti‐ESM1 antibodies overcome tumor bevacizumab resistance by suppressing angiogenesis and metastasis

“…Multiple studies have indicated that high levels of DLL4 expression 10 , particularly within tumor tissue, are positively correlated with tumor invasiveness and poor prognosis in patients with colorectal cancer, gastric cancer, and breast cancer. 11 , 12 , 13 The study found a major correlation between increased DLL4 expression in ovarian cancer patients 14 and increased Notch intracellular cleaved domain (NICD) in colorectal cancer patients with a poor response to anti‐VEGF therapy. 3 Moreover, studies have shown that inhibiting the Notch/DLL4/Hes pathway can lead to a decrease in angiogenesis and tumor growth in human colon tumors.…”

“…Numerous clinical tumor models have demonstrated a strong correlation between DLL4 expression and tumor progression, as well as treatment resistance. Multiple studies have indicated that high levels of DLL4 expression 10 , particularly within tumor tissue, are positively correlated with tumor invasiveness and poor prognosis in patients with colorectal cancer, gastric cancer, and breast cancer 11‐13 . The study found a major correlation between increased DLL4 expression in ovarian cancer patients 14 and increased Notch intracellular cleaved domain (NICD) in colorectal cancer patients with a poor response to anti‐VEGF therapy 3 .…”