Potential Association of Poly(ADP-ribose) Polymerase-1 (PARP-1) with CD133 and G2/M as Independent Predictors in Colorectal Cancer Development.

Abstract

Objective: PARP inhibitor therapy was intensively investigated in colorectal cancer (CRC). Therefore, our aim was to investigate the potential association of DNA repair protein PARP-1 with cancer stem cell CD133 and DNA cell cycle abnormalities in colorectal cancer patients and ulcerative colitis (UC) as a diagnostic tool for differential diagnosis, evaluation of tumor progression and prediction of patient's disease outcome to benefit in therapeutic response. Materials and Methods: Thirty seven (20 colorectal cancer and 17 Ulcerative colitis) patients and ten tissue specimens of normal colon mucosa used as non-disease control group. Tissue specimens from all individuals were collected at surgery and examined for PARP-1, CD133 and DNA Cell cycle by flow cytometry. Results: CD133 and PARP-1 were gradually increased from UC to CRC (p<0.0001) in CD133 and PARP-1 (p=0.02). DNA cell cycle abnormalities showed significant difference between CRC and UC groups only in G2/M (p<0.0001). CRC showed higher expression of CD133 in Stage III compared to stage I (p=0.01) but the difference in tumor site was recorded between transverse colon and rectum in S phase (p=0.04) and G0/1 (p=0.016) and between transverse and Lt Colon in G0/1 (p=0.016). Multiple regressions for PARP-1, CD133 and G2/M showed higher prediction for CRC progression. Conclusion: PARP-1, CD133 and G2/M could be considered as additional biomarkers to increase the diagnostic potential in CRC patients, in predicting tumor development and monitoring therapeutic response.