Kugimiya Naruji, Harada Eijiro, Suehiro Yuki, Suga Atsushi, Takemoto Yoshihiro, Hamano Kimikazu
Department of Surgery and Clinical Science, Yamaguchi University Graduate School of Medicine, Ube, Yamaguchi 755-8505, Japan.
Oncol Lett. 2019 Jun;17(6):5267-5274. doi: 10.3892/ol.2019.10181. Epub 2019 Mar 21.
The present study aimed to prospectively clarify the prognostic effect of the expression of several genes that are known to modulate 5-fluorouracil effects in 63 patients who underwent curative resection for stage II/III colorectal cancer following adjuvant chemotherapy with oral fluoropyrimidines between 2008 and 2012. Thymidine phosphorylase (TP) expression in primary tumours was significantly lower in the recurrence group compared with the no-recurrence group (P=0.03), whereas, expression levels of genes that encoded thymidylate synthase, dihydropyrimidine dehydrogenase, folylpolyglutamate synthase, γ-glutamyl hydrolase and dihydrofolate reductase were not statistically different in tumours from the recurrence and no-recurrence groups. In the multivariate analysis using stepwise Cox proportional hazards regression, the following factors were significantly associated with shorter relapse-free survival following adjuvant chemotherapy with oral fluoropyrimidines: Venous invasion [present; hazard ratio (HR)=6.51; 95% confidence interval (CI): 1.55-27.4; P=0.01), Tumour-Node-Metastasis stage (3b; HR=6.18; 95% CI: 1.36-28.2; P=0.02) and TP expression (low; HR=9.61; 95% CI: 1.81-51.0; P=0.04). Patients with two or more risk characteristics had significantly shorter 5-year relapse-free survival compared with patients with one or no risk characteristics (55.8 vs. 91.8%; log-rank P=0.0006). We concluded that low TP expression is an independent predictive factor for poor prognosis in colorectal cancer. Therefore, determining TP expression may help to improve recurrence risk stratification in patients with stage II/III colorectal cancer following adjuvant chemotherapy with oral fluoropyrimidines.
本研究旨在前瞻性地阐明在2008年至2012年间接受口服氟嘧啶辅助化疗后进行了II/III期结直肠癌根治性切除的63例患者中，几种已知可调节5-氟尿嘧啶作用的基因表达的预后影响。复发组原发肿瘤中胸苷磷酸化酶（TP）的表达明显低于无复发组（P = 0.03），而编码胸苷酸合成酶、二氢嘧啶脱氢酶、叶酰聚谷氨酸合成酶、γ-谷氨酰水解酶和二氢叶酸还原酶的基因表达水平在复发组和无复发组的肿瘤中无统计学差异。在使用逐步Cox比例风险回归的多变量分析中，以下因素与口服氟嘧啶辅助化疗后无复发生存期缩短显著相关：静脉侵犯[存在；风险比（HR）= 6.51；95%置信区间（CI）：1.55 - 27.4；P = 0.01]、肿瘤-淋巴结-转移分期（3b；HR = 6.18；95% CI：1.36 - 28.2；P = 0.02）和TP表达（低；HR = 9.61；95% CI：1.81 - 51.0；P = 0.04）。具有两个或更多风险特征的患者与具有一个或无风险特征的患者相比，5年无复发生存期明显更短（55.8%对91.8%；对数秩P = 0.0006）。我们得出结论，低TP表达是结直肠癌预后不良的独立预测因素。因此，测定TP表达可能有助于改善口服氟嘧啶辅助化疗后的II/III期结直肠癌患者的复发风险分层。
