Ide Hiroki, Kikuchi Eiji, Mikami Shuji, Miyajima Akira, Oya Mototsugu
Department of Urology and Pathology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan.
BMC Res Notes. 2014 Sep 13;7:646. doi: 10.1186/1756-0500-7-646.
Recently, it has been shown that 5-fluorouracil (5-FU) with a strong dihydropyrimidine dehydrogenase (DPD) inhibitor elicits a significant response in bladder cancer with a high level of DPD. However, only a few studies investigated the association between the level of the enzyme that regulates the metabolism of 5-FU and prognosis in bladder cancer. Furthermore, to our knowledge, there has also been no such report in T1G3 bladder tumors treated with BCG. Therefore, we evaluated enzymes that regulate the metabolism of 5-FU in T1G3 tumors treated with BCG immunotherapy using the Danenberg tumor profile (DTP) method, a highly accurate measurement of RNA from paraffin-embedded specimens.
This study included 28 patients with T1G3 bladder cancer, each of whom underwent complete transurethral tumor resection and BCG intravesical instillation at our institution. The median follow-up period was 39 months (range, 3 to 159 months). The DTP method was used to analyze the mRNA expression of 3 enzymes related to 5-FU: DPD, orotate phosphoribosyltransferase (OPRT), and thymidylate synthase (TS).
Among the 28 patients, 13 developed recurrences (46.4%) and 5 experienced disease progression (17.9%). An elevated DPD mRNA level was significantly associated with recurrence (p = 0.048) and progression (p = 0.045). However, TS and OPRT mRNA levels were not significantly associated with any other clinical features or outcomes. Furthermore, the high DPD group had a significantly lower recurrence-free survival rate than the low DPD group (p = 0.047). Among patients with low DPD, the 2- and 5-year recurrence-free survival rates were 88.9% and 74.1%, respectively; while among patients with high DPD, the corresponding rates were 61.3% and 36.8%, respectively. TS and OPRT were not significantly associated with recurrence-free survival rates.
DPD is significantly associated with recurrence and progression among T1G3 bladder cancer patients treated with BCG.
最近有研究表明，5-氟尿嘧啶（5-FU）与强效二氢嘧啶脱氢酶（DPD）抑制剂联合使用时，对DPD水平较高的膀胱癌有显著疗效。然而，仅有少数研究探讨了调节5-FU代谢的酶水平与膀胱癌预后之间的关系。此外，据我们所知，对于接受卡介苗（BCG）治疗的T1G3膀胱肿瘤，尚无此类报道。因此，我们使用丹嫩贝格肿瘤谱（DTP）方法评估了接受BCG免疫治疗的T1G3肿瘤中调节5-FU代谢的酶，该方法可对石蜡包埋标本中的RNA进行高度精确的测量。
本研究纳入了28例T1G3膀胱癌患者，每位患者均在我们机构接受了经尿道肿瘤全切术及膀胱内BCG灌注。中位随访期为39个月（范围3至159个月）。采用DTP方法分析与5-FU相关的3种酶的mRNA表达：DPD、乳清酸磷酸核糖转移酶（OPRT）和胸苷酸合成酶（TS）。
28例患者中，13例复发（46.4%）且5例病情进展（17.9%）。DPD mRNA水平升高与复发（p = 0.048）和进展（p = 0.045）显著相关。然而，TS和OPRT mRNA水平与任何其他临床特征或结局均无显著关联。此外，高DPD组的无复发生存率显著低于低DPD组（p = 0.047）。在低DPD患者中，2年和5年无复发生存率分别为88.9%和74.1%；而在高DPD患者中，相应的比率分别为61.3%和36.8%。TS和OPRT与无复发生存率无显著关联。
在接受BCG治疗的T1G3膀胱癌患者中，DPD与复发和进展显著相关。
