Department of pharmacy, Affiliated hospital of Zunyi Medical University, Guizhou, 563003, China.
Department of Clinical Pharmacy, West China School of Pharmacy, Sichuan University, No. 3, section 17, Renmin South Road, Wuhou District, Chengdu City, 610041, Sichuan, China.
Int J Colorectal Dis. 2019 Dec;34(12):2151-2159. doi: 10.1007/s00384-019-03407-x. Epub 2019 Nov 16.
To investigate the influence of organic cation transporter 3 (OCT3) expression on the effect of the combination regimen of 5-fluorouracil, folinic acid and oxaliplatin ((m)FOLFOX6) in colorectal cancer (CRC) patients.
This is a retrospective study conducted at a single centre (Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, China). Patients with stage IIb-IV resectable CRC who were being postoperatively treated with (m)FOLFOX6 as a first-line adjuvant chemotherapy regimen for at least 5 cycles and had resected primary tumour samples available were eligible for the study. Patients who preoperatively received chemotherapy and/or radiotherapy or were treated with targeted drugs or other anticancer drugs were excluded from the study. Immunohistochemical staining and digital image analysis were used to assess OCT3 expression in tumour samples. According to OCT3 expression level, the receiver operating characteristic curve (ROC curve) was used to divide the patients into two groups. Cox proportional risk regression was performed with the forward LR (forward stepwise regression based on maximum likelihood estimation) method using SPSS17.0 software. The primary endpoint was the 2-year progression-free survival.
In total, 57 patients were included between 2014 and 2016 according to the inclusion and exclusion criteria (22 had low OCT3 expression, and 35 had high OCT3 expression). The mean age was 55.7 (30-74) years, and 37 of the total patients were male. According to TNM stage, 5 patients had stage IV disease, 44 patients had stage III disease, and 8 patients had stage II disease. Through Cox regression analysis, we found that among patients receiving the (m)FOLFOX6 regimen, those with higher OCT3 expression had a higher two-year progression-free survival rate than those with lower OCT3 expression (P = 0.038). The hazard ratio of patients with high OCT3 expression compared with patients with low OCT3 expression was 0.247. Besides, it was found that the age of patients was negatively correlated with expression level of OCT3, which can explain why patients over 70 years do not benefit from oxaliplatin-containing chemotherapy.
High OCT3 expression in CRC tissues may be a protective factor for CRC patients treated with (m)FOLFOX6.
研究有机阳离子转运蛋白 3（OCT3）表达对氟尿嘧啶、亚叶酸钙和奥沙利铂联合方案（m）FOLFOX6 治疗结直肠癌（CRC）患者疗效的影响。
这是一项在中国一个中心（四川省医学科学院·四川省人民医院）进行的回顾性研究。该研究纳入了接受 m）FOLFOX6 作为一线辅助化疗方案（至少 5 个周期）且可获得切除的原发肿瘤样本的 IIb-IV 期可切除 CRC 患者。排除术前接受化疗和/或放疗、接受靶向药物或其他抗癌药物治疗的患者。采用免疫组织化学染色和数字图像分析评估肿瘤样本中 OCT3 的表达。根据 OCT3 表达水平，采用受试者工作特征曲线（ROC 曲线）将患者分为两组。采用 SPSS17.0 软件通过向前 LR（基于最大似然估计的向前逐步回归）方法进行 Cox 比例风险回归。主要终点是 2 年无进展生存率。
根据纳入和排除标准，共有 57 例患者于 2014 年至 2016 年被纳入研究（22 例患者 OCT3 低表达，35 例患者 OCT3 高表达）。患者平均年龄为 55.7（30-74）岁，其中 37 例患者为男性。根据 TNM 分期，5 例患者为 IV 期疾病，44 例患者为 III 期疾病，8 例患者为 II 期疾病。通过 Cox 回归分析，我们发现，在接受 m）FOLFOX6 方案治疗的患者中，OCT3 高表达患者的 2 年无进展生存率高于 OCT3 低表达患者（P=0.038）。与 OCT3 低表达患者相比，OCT3 高表达患者的风险比为 0.247。此外，我们发现患者的年龄与 OCT3 的表达水平呈负相关，这可以解释为什么 70 岁以上的患者不能从含奥沙利铂的化疗中获益。
CRC 组织中 OCT3 的高表达可能是接受 m）FOLFOX6 治疗的 CRC 患者的保护因素。
