Abstract A54: Possible targets of metformin in colorectal cancer

Abstract

Abstract Background: Growing evidence suggests metformin improves survival in diabetic colorectal cancer (CRC) patients. However, the mechanism of action remains unclear. In order to explore the mechanistic relationship between metformin and colon cancer, we examined the expression levels of several proteins implicated in metformin's action. Methods: We collected clinical-pathological and outcomes data on all CRC patients treated at the University of Chicago (UC) from 2006-2010. The data was collected through UC cancer registry and chart review. Diabetic CRC patients and matched controls (matched on race and stage) were selected for immunostaining (IHC). Tissues blocks (FFPE) were retrieved and tissue microarray (TMA) were constructed. IHC was performed for pAMPK, pmTOR, p70S6K, 4E-BP1, pAKT, IGF1R, beta-Catenin and Ki-67. Total score was calculated from the intensity and percentage scoring. The results were analyzed in two groups: diabetic CRC patients on metformin (group 1) and diabetic or non-diabetic CRC patients not on metformin (group 2). Chi-square test was done for estimating statistical significance between groups keeping a level of significance at 10% (alpha < 0.10). Results: The mean age of CRC patients was 62.7 years, 49% were males. Out of a total of 700 patients, 79 (11.21%) were diabetic. Metformin was prescribed to 40.5% of diabetic patients. Only 52 diabetics have FFPE block available so TMA was constructed with 104 patients in total (52 cases and 52 controls). Immunostaining was analyzable for a total of 84 patients. There were 18 and 66 patients in group 1 and 2, respectively. We found a lower expression of Ki-67 in the metformin group (group 1; 39%) as compared to non-metformin group (group 2; 64%) which was statistically significant (p = 0.04). IGF1R and beta-Catenin showed a higher expression in non-metformin group (89% and 95%, respectively) as compared to metformin group (72% and 83%, respectively) which was close to significance (p=0.12 and p=0.13, respectively). There was no significant difference between the expression of pAMPK, pmTOR, p70S6K, 4E-BP1 and pAKT in the two groups. Conclusions: Metformin appears to improve the survival of CRC patients by decreasing proliferation. The results need to be validated in a larger study. Citation Format: Amikar Sehdev, Galina Khramtsova, Nora Joseph, Blase P. Polite, Marc B. Bissonnette, Olopade I. Olufunmilayo. Possible targets of metformin in colorectal cancer. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A54.