Abstract
The angiogenic proteins vascular endothelial growth factor (VEGF) and prokineticin1 (PROK1) proteins are considered important in colorectal cancer, the relationship between their simultaneous expression and prognosis was investigated in the present study. VEGF and PROK1 expression in 620 primary human colorectal cancer lesions was confirmed via immunohistochemical staining with anti-VEGF and anti-PROK1 antibodies, and the correlation between the expression of these 2 proteins and recurrence/prognosis were investigated. VEGF protein was expressed in 329 (53.1%) and PROK1 protein was expressed in 223 (36.0%). PROK1 and VEGF were simultaneously expressed in 116 (18.7%) of the 620 cases. The correlation coefficient between VEGF expression and PROK1 expression was r = 0.11, and therefore correlation was not observed. Clinical pathology revealed that substantially lymphnode matastasis, hematogenous metastasis, or TMN advanced-stage IV was significantly more prevalent in cases that expressed both VEGF and PROK1 than in the cases negative for both proteins or those positive for only 1 of the proteins. Also the cases positive for both proteins exhibited the worst recurrence and prognosis. In the Cox proportional hazards model, VEGF and PROK1 expression was an independent prognostic factor. The prognosis was poorer in colorectal cancers that expressed both PROK1 and VEGF relative to the cases that expressed only 1 protein, and the expression of both proteins was found to be an independent prognostic factor.
Highlights
The therapeutic outcomes are relatively favorable for early-stage colorectal cancer but unsatisfactory for advanced cases, a phenomenon that requires further investigation [1]
Gastrointestinal cancer and other various malignant tumors have been investigated via molecular biological techniques, and a considerable number of genes are thought to be involved in the metastatic and growth mechanisms [29, 30]
The most well known vascular endothelial growth factor (VEGF) was found to correlate with the hematogenous metastasis of gastric and colorectal cancers [16,17,18], and elevated VEGF expression induced angiogenesis near the tumor
Summary
The therapeutic outcomes are relatively favorable for early-stage colorectal cancer but unsatisfactory for advanced (stage III/IV) cases, a phenomenon that requires further investigation [1]. The determining prognostic factor in colorectal cancer is hematogenous metastasis, including liver metastasis [1]. Various molecular biological investigations of hematogenous mechanisms have revealed the following process in which angiogenic factors are closely involved during multiple steps [2,3,4,5]: cancer cells dissociate from the primary lesion, followed by basement membrane disintegration, movement within the interstitium, vascular invasion, and cancer cell adhesion, invasion, and proliferation in the target organ [6]. Cancer cells can directly produce angiogenic growth factors or proteases and release extracellular matrix (ECM)-bound vascular endothelial growth factor (VEGF) to stimulate the www.impactjournals.com/oncotarget vessels and induce angiogenesis [9,10]. The current National Comprehensive Cancer Network (NCCN) guidelines include anti-VEGF antibody therapy in addition to systemic FOLFOX (folinic acid/5-fluorouracil/oxaliplatin) and FOLFIRI (folinic acid/5-fluorouracil/irinotecan) chemotherapy for the treatment of unresectable/recurrent colorectal cancer [20]
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