Soh Junichi, Yamamoto Hiromasa, Okumura Norihito, Suzuki Hiroyuki, Nakata Masao, Fujiwara Toshiya, Gemba Kenicehi, Sano Isao, Fujinaga Takuji, Kataoka Masafumi, Terasaki Yasuhiro, Fujimoto Nobukazu, Kataoka Kazuhiko, Kosaka Shinji, Yamashita Motohiro, Inokawa Hidetoshi, Inoue Masaaki, Nakamura Hiroshige, Yamashita Yoshinori, Takahashi Yuta, Torigoe Hidejiro, Sato Hiroki, Tomida Shuta, Hotta Katsuyuki, Yoshioka Hiroshige, Morita Satoshi, Matsuo Keitaro, Sakamoto Junichi, Date Hiroshi, Toyooka Shinichi
Department of Thoracic Surgery, Okayama University Hospital, Okayama 700-8558, Japan.
Department of Thoracic Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka 545-8585, Japan.
Mol Clin Oncol. 2025 Jul 3;23(3):79. doi: 10.3892/mco.2025.2874. eCollection 2025 Sep.
Managing elderly patients presents several challenges because of age-related declines; however, age should not be the sole determinant for adjuvant treatment decisions in patients with non-small cell lung cancer (NSCLC). Moreover, age may affect the expression of 5-fluorouracil (5-FU) biomarkers. The present study assessed: i) The effect of age on the expression levels of 5-FU biomarkers by analyzing a public database; and ii) the ability of these biomarkers to predict clinical outcomes in elderly patients with NSCLC who underwent complete resection in the Setouchi Lung Cancer Group Study 1201 (SCLG1201) followed by S-1 adjuvant chemotherapy. Changes in gene expression levels across age groups were assessed by analyzing The Cancer Genome Atlas (TCGA) database. The expression of 5-FU biomarkers, including thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyltransferase, epidermal growth factor receptor (EGFR) and excision repair cross-complementation group 1 (ERCC1), were assessed via quantitative reverse-transcription PCR assays in 89 elderly patients (≥75 years) with NSCLC who received adjuvant chemotherapy with oral fluoropyrimidine prodrug S-1 in the SLCG1201 trial. TCGA database analysis (n=955) showed that expression decreased significantly with aging, especially in the age group ≥75. In the SCLG1201 trial, univariate analysis revealed that upregulation and downregulation were correlated with favorable recurrence-free survival (RFS) and overall survival (OS), respectively. Multivariate analysis demonstrated that pathological stage was an independent prognostic factor for both RFS and OS. mutations were associated with upregulation of and , and downregulation of and . In conclusion, although pathological stage is an independent prognostic factor for survival, upregulation and downregulation may be a greater predictor of clinical outcomes in elderly patients with NSCLC treated with S-1 adjuvant chemotherapy. The age-related decrease in TS expression supports the potential benefit of 5-FU therapies in elderly patients. Nonetheless, further research is warranted to validate these results.
由于与年龄相关的机能衰退，管理老年患者面临诸多挑战；然而，年龄不应成为非小细胞肺癌（NSCLC）患者辅助治疗决策的唯一决定因素。此外，年龄可能会影响5-氟尿嘧啶（5-FU）生物标志物的表达。本研究评估了：i）通过分析一个公共数据库，年龄对5-FU生物标志物表达水平的影响；ii）在濑户内肺癌组研究1201（SCLG1201）中接受完全切除并随后接受S-1辅助化疗的老年NSCLC患者中，这些生物标志物预测临床结局的能力。通过分析癌症基因组图谱（TCGA）数据库评估各年龄组基因表达水平的变化。在SLCG1201试验中，对89例接受口服氟嘧啶前体药物S-1辅助化疗的老年（≥75岁）NSCLC患者，通过定量逆转录PCR分析评估5-FU生物标志物的表达，这些生物标志物包括胸苷酸合成酶（TS）、二氢嘧啶脱氢酶（DPD）、乳清酸磷酸核糖基转移酶、表皮生长因子受体（EGFR）和切除修复交叉互补组1（ERCC1）。TCGA数据库分析（n = 955）显示，表达随年龄增长显著下降，尤其是在≥75岁年龄组。在SCLG1201试验中，单因素分析显示，上调和下调分别与无复发生存期（RFS）和总生存期（OS）良好相关。多因素分析表明，病理分期是RFS和OS的独立预后因素。 突变与 的上调、 的上调以及 的下调、 的下调相关。总之，尽管病理分期是生存的独立预后因素，但上调和下调可能是接受S-1辅助化疗的老年NSCLC患者临床结局的更强预测指标。TS表达随年龄下降支持5-FU疗法对老年患者的潜在益处。尽管如此，仍需进一步研究来验证这些结果。
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