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The Prognostic Significance of 5-Fluorouracil Induced Inflammation and Immuno-Modulation in Colorectal Cancer Patients
Journal of Inflammation Research ( IF 4.2 ) Pub Date : 2020-12-31 , DOI: 10.2147/jir.s283069 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 Fouad 3
Journal of Inflammation Research ( IF 4.2 ) Pub Date : 2020-12-31 , DOI: 10.2147/jir.s283069 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 Fouad 3
Affiliation
Aim: 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
中文翻译：
5-氟尿嘧啶诱导的结直肠癌患者炎症和免疫调节的预后意义
目的：评估与 5-氟尿嘧啶 (5-FU) 治疗相关的外周炎症标志物和 EGFR 水平的变化在结直肠癌 (CRC) 患者中的预后意义。
患者和方法：通过定量实时 PCR (qPCR) 测定 90 名 CRC 患者外周血中 COX2、IL6、IL1β、EGFR、IL10 和 TNFα 的表达水平。炎症反应与患者的临床特征、无病生存期（DFS）和总生存期（OS）相关。
结果：5-FU 治疗 6 个月后，发现炎症反应增加与吸烟、T3 或 T4 肿瘤、体能状态 (PS) III、淋巴结阳性、远处转移和胃肠道 (GIT) 毒性有关。在 EGFR 过表达的患者中，COX2 与白细胞介素在 DFS 预测方程中的组合是显着的。使用 5-FU 治疗的 COX2、IL6、IL10 和 TNFα 表达增加的患者的 DFS 和 OS 率降低。疾病进展的显着危险与吸烟（HR=1.27，P =0.004）、5-FU 诱导 COX2 和 IL6 表达（HR=1.35，P =0.001 和 HR=1.27，P= 0.004，分别）。此外，吸烟、5-FU 诱导的 IL6、TNFα 和 IL10 表达被发现是 OS 的独立预后因素（分别为P = 0.003、0.003、0.002 和 0.002）。
结论： 5-FU治疗的外周效应对CRC患者的治疗结果有显着影响。
关键词：结直肠癌，5-氟尿嘧啶，COX2，EGFR，白细胞介素，存活，TNFα
更新日期：2020-12-31
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
中文翻译：
5-氟尿嘧啶诱导的结直肠癌患者炎症和免疫调节的预后意义
目的：评估与 5-氟尿嘧啶 (5-FU) 治疗相关的外周炎症标志物和 EGFR 水平的变化在结直肠癌 (CRC) 患者中的预后意义。
患者和方法：通过定量实时 PCR (qPCR) 测定 90 名 CRC 患者外周血中 COX2、IL6、IL1β、EGFR、IL10 和 TNFα 的表达水平。炎症反应与患者的临床特征、无病生存期（DFS）和总生存期（OS）相关。
结果：5-FU 治疗 6 个月后，发现炎症反应增加与吸烟、T3 或 T4 肿瘤、体能状态 (PS) III、淋巴结阳性、远处转移和胃肠道 (GIT) 毒性有关。在 EGFR 过表达的患者中，COX2 与白细胞介素在 DFS 预测方程中的组合是显着的。使用 5-FU 治疗的 COX2、IL6、IL10 和 TNFα 表达增加的患者的 DFS 和 OS 率降低。疾病进展的显着危险与吸烟（HR=1.27，P =0.004）、5-FU 诱导 COX2 和 IL6 表达（HR=1.35，P =0.001 和 HR=1.27，P= 0.004，分别）。此外，吸烟、5-FU 诱导的 IL6、TNFα 和 IL10 表达被发现是 OS 的独立预后因素（分别为P = 0.003、0.003、0.002 和 0.002）。
结论： 5-FU治疗的外周效应对CRC患者的治疗结果有显着影响。
关键词：结直肠癌，5-氟尿嘧啶，COX2，EGFR，白细胞介素，存活，TNFα
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