Supplementary Material for: Prognostic Impact of the ABCC11/MRP8 Polymorphism in Adjuvant Oral Chemotherapy with S-1 for Non-Small Cell Lung Cancer

Background: Postoperative 1-year administration of S-1, an oral derivative of 5-fluorouracil (5-FU), was shown to be feasible in lung cancer. The 5-year survival rates of postoperative patients treated with S-1 adjuvant chemotherapy and the prognostic impact of clinicopathological factors were examined. Methods: The data of 50 patients with curatively resected pathological stage IB to IIIA non-small cell lung cancer, who were treated with S-1 postoperatively, were analyzed. The prognostic impacts of 22 clinicopathological factors including expressions of the 5-FU pathway enzymes were evaluated. A single-nucleotide polymorphism (SNP), i.e. 538G>A (rs17822931), of ABCC11/MRP8, which encodes a 5-FU excretion enzyme that is known as an earwax type determinant, was also evaluated. Results: The 5-year overall and relapse-free survival rates were 72.5 and 67.5%, respectively. A performance status ≥1, lymphatic vessel invasion, blood vessel invasion, and the A/A type of SNP538, which is responsible for the dry earwax type, were significantly associated with shorter relapse-free survivals. In 34 patients who showed a relative performance of 70% or more for chemotherapy, multivariate survival analysis indicated significant hazard ratios only for the A/A type of SNP538 (p = 0.007). Conclusions: S-1 has sufficient power as adjuvant chemotherapy. However, its effect might be small in the dry earwax type patient group in an adjuvant setting.

背景：术后1年口服给予S-1——5-氟尿嘧啶（5-fluorouracil，5-FU）的口服衍生物——在肺癌患者中已被证实具备临床可行性。本研究旨在探讨接受S-1辅助化疗的术后肺癌患者的5年生存率，以及临床病理因素对预后的影响。
方法：本研究分析了50例接受术后S-1辅助治疗的根治性切除术后病理分期IB至IIIA期非小细胞肺癌患者的临床资料。研究评估了包括5-FU代谢通路酶表达在内的22项临床病理因素的预后价值，并对编码5-FU排泄酶（同时作为耳垢类型决定因子）的ABCC11/MRP8基因的单核苷酸多态性（single-nucleotide polymorphism，SNP）538G>A（rs17822931）进行了分析。
结果：患者的5年总生存率与无复发生存率分别为72.5%和67.5%。体力状况评分≥1、淋巴管浸润、血管浸润，以及对应干性耳垢表型的SNP538 A/A基因型，均与更短的无复发生存期显著相关。在34例化疗相关体能状态≥70%的患者中，多因素生存分析显示仅SNP538 A/A基因型具有显著的风险比（p=0.007）。
结论：S-1作为辅助化疗方案具备充足的临床疗效。但在辅助治疗场景下，干性耳垢表型患者群体对其应答效果或较为有限。