Jane Jijun Liu1, Mihaela Druta1, David Shibata2, Domenico Coppola3, Ivette Boler4, Abul Elahi2, Richard R Reich5, Erin Siegel6, Martine Extermann7. 1. Department of Hematology and Medical Oncology, Moffitt Cancer Center, United States. 2. Department of Gastrointestinal Oncology, Moffitt Cancer Center, United States. 3. Department of Anatomic Pathology, Moffitt Cancer Center, United States; Experimental Therapeutics, Moffitt Cancer Center, United States. 4. Senior Adult Oncology Program, Moffitt Cancer Center, United States. 5. Department of Biostatistics, Moffitt Cancer Center, United States; College of Arts and Sciences, University of South Florida Sarasota-Manatee, United States. 6. Department of Cancer Prevention and Control, Moffitt Cancer Center, United States. 7. Senior Adult Oncology Program, Moffitt Cancer Center, United States. Electronic address: martine.extermann@moffitt.org.
Abstract
OBJECTIVE: Components of metabolic syndrome (MS) have been individually linked to colorectal cancer risk and prognosis; however, an understanding of the dominant mechanisms is lacking. MATERIALS AND METHODS: Twenty-one patients (10 MS; 11 non-MS) with resectable colorectal cancer were prospectively enrolled. Patients were classified for MS by the World Health Organization criteria and tested for circulating vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), fasting insulin, and tumor expression of IGF-1 receptor (IGF-1R), insulin-receptor (IR) and receptor for advanced glycation end-products (RAGE). Circulating markers were re-tested 6 months after surgery. RESULTS: The MS group had significantly higher baseline and post-operative fasting insulin levels (p < 0.001 and 0.003). No differences were observed in circulating IL-6, VEGF, IGF-1 and free IGF-1. By immunohistochemistry (IHC), IGF-1R expression was significantly higher in tumor vs. normal tissues (p < 0.001) while IR expression showed no difference. Interestingly, 64% of tumors demonstrated high IR positivity in the vessels within or surrounding the tumor stroma, but not in the vessels away from the tumor. By reverse transcription polymerase chain reaction (RT-PCR), tumor IGF-1R over-expression (80%) was confirmed, but there was no difference between MS and non-MS patients. Tumor RAGE over-expression was found in 67% of patients and was equally distributed between the two groups. CONCLUSIONS: Hyperinsulinemia was the only significant factor distinguishing patients with colorectal cancer who have MS. The preferential over-expression of IR in the peri-tumoral microvessels suggests that hyperinsulinemia might contribute to colorectal cancer growth by enhancing angiogenesis.
OBJECTIVE: Components of metabolic syndrome (MS) have been individually linked to colorectal cancer risk and prognosis; however, an understanding of the dominant mechanisms is lacking. MATERIALS AND METHODS: Twenty-one patients (10 MS; 11 non-MS) with resectable colorectal cancer were prospectively enrolled. Patients were classified for MS by the World Health Organization criteria and tested for circulating vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), insulin-like growth factor-1 (IGF-1), fasting insulin, and tumor expression of IGF-1 receptor (IGF-1R), insulin-receptor (IR) and receptor for advanced glycation end-products (RAGE). Circulating markers were re-tested 6 months after surgery. RESULTS: The MS group had significantly higher baseline and post-operative fasting insulin levels (p < 0.001 and 0.003). No differences were observed in circulating IL-6, VEGF, IGF-1 and free IGF-1. By immunohistochemistry (IHC), IGF-1R expression was significantly higher in tumor vs. normal tissues (p < 0.001) while IR expression showed no difference. Interestingly, 64% of tumors demonstrated high IR positivity in the vessels within or surrounding the tumor stroma, but not in the vessels away from the tumor. By reverse transcription polymerase chain reaction (RT-PCR), tumorIGF-1R over-expression (80%) was confirmed, but there was no difference between MS and non-MS patients. TumorRAGE over-expression was found in 67% of patients and was equally distributed between the two groups. CONCLUSIONS:Hyperinsulinemia was the only significant factor distinguishing patients with colorectal cancer who have MS. The preferential over-expression of IR in the peri-tumoral microvessels suggests that hyperinsulinemia might contribute to colorectal cancer growth by enhancing angiogenesis.
Authors: Laura A Colangelo; Susan M Gapstur; Peter H Gann; Alan R Dyer; Kiang Liu Journal: Cancer Epidemiol Biomarkers Prev Date: 2002-04 Impact factor: 4.254
Authors: Cornelia M Ulrich; Biljana Gigic; Graham A Colditz; Jane C Figueiredo; William M Grady; Christopher I Li; David Shibata; Erin M Siegel; Adetunji T Toriola; Alexis Ulrich; Jürgen Böhm; Jennifer Ose; Richard Viskochil; Martin Schneider Journal: Cancer Epidemiol Biomarkers Prev Date: 2018-12-06 Impact factor: 4.254