The Prognostic Significance of 5-Fluorouracil Induced Inflammation and Immuno-Modulation in Colorectal Cancer Patients

Abstract

Mona S Abdellateif,1 Salem E Salem,2 Doaa M Badr,3 Sabry Shaarawy,1 Marwa M Hussein,2 Abdel-Rahman N Zekri,4 Mariam A Fouad3 1Medical Biochemistry and Molecular Biology, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt; 2Medical Oncology Department, National Cancer Institute, Cairo, Egypt; 3Pharmacology and Experimental Oncology Unit, Cancer Biology Department, National Cancer Institute, Cairo University, Cairo, Egypt; 4Virology and Immunology Unit, Cancer Biology Department, National Cancer Institute, Cairo, EgyptCorrespondence: Mariam A FouadPharmacology and Experimental Oncology Unit, Cancer Biology Department, National Cairo Institute, Cairo University, 1Kasr AlAini Street, Fom Elkalig, Cairo 11796, EgyptEmail [email protected]: The change in the levels of peripheral inflammatory markers together with EGFR in relation to 5- fluorouracil (5-FU) therapy was evaluated for their prognostic significance in colorectal cancer (CRC) patients.Patients and Methods: Expression levels of COX2, IL6, IL1β, EGFR, IL10, and TNFα were determined with quantitative real-time PCR (qPCR) in the peripheral blood of 90 CRC patients. The inflammatory response was correlated with patients’ clinical features, disease-free survival (DFS), and overall survival (OS).Results: After 6 months of 5-FU therapy, increased inflammatory response was found to be associated with smoking, T3 or T4 tumors, performance status (PS) III, positive lymph nodes, distant metastasis, and gastrointestinal (GIT) toxicity. The combination of COX2 with interleukins in a predictive equation for DFS was significant in patients with over-expression of EGFR. DFS and OS rates were reduced in patients with increased COX2, IL6, IL10, and TNFα expression with 5-FU therapy. Significant hazard of disease progression was associated with smoking (HR=1.27, P=0.004), 5-FU induction of COX2, and IL6 expression (HR=1.35, P=0.001 and HR=1.27, P=0.004, respectively). Moreover, smoking, 5-FU induction of IL6, TNFα, and IL10 expression are found to be independent prognostic factors for OS (P=0.003, 0.003, 0.002, and 0.002, respectively).Conclusion: The peripheral effects of 5-FU therapy have shown a significant impact on the treatment outcome of CRC patients.Keywords: colorectal cancer, 5-fluorouracil, COX2, EGFR, interleukins, survival, TNFα

Keywords

• colorectal cancer
• 5- fluorouracil
• cox2
• egfr
• interleukins
• survival
• tnfα.