Stubbe Benjamin Emil, Larsen Anders Christian, Madsen Poul Henning, Krarup Henrik Bygum, Pedersen Inge Søkilde, Lundbye-Christensen Søren, Hansen Carsten Palnæs, Hasselby Jane Preuss, Johansen Astrid Zedlitz, Thorlacius-Ussing Ole, Johansen Julia Sidenius, Henriksen Stine Dam
Department of Gastrointestinal Surgery, Aalborg University Hospital, Aalborg, Denmark.
Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
Front Oncol. 2023 Jun 2;13:1211292. doi: 10.3389/fonc.2023.1211292. eCollection 2023.
Current prognostic blood-based biomarkers for pancreatic adenocarcinoma (PDAC) are limited. Recently, promoter hypermethylation of SFRP1 (phSFRP1) has been linked to poor prognosis in patients with gemcitabine-treated stage IV PDAC. This study explores the effects of phSFRP1 in patients with lower stage PDAC.
Based on a bisulfite treatment process, the promoter region of the SFRP1 gene was analyzed with methylation-specific PCR. Kaplan-Meier curves, log-rank tests, and generalized linear regression analysis were used to assess restricted mean survival time survival at 12 and 24 months.
The study included 211 patients with stage I-II PDAC. The median overall survival of patients with phSFRP1 was 13.1 months, compared to 19.6 months in patients with unmethylated SFRP1 (umSFRP1). In adjusted analysis, phSFRP1 was associated with a loss of 1.15 months (95%CI -2.11, -0.20) and 2.71 months (95%CI -2.71, -0.45) of life at 12 and 24 months, respectively. There was no significant effect of phSFRP1 on disease-free or progression-free survival. In stage I-II PDAC, patients with phSFRP1 have worse prognoses than patients with umSFRP1.
Results could indicate that the poor prognosis may be caused by reduced benefit from adjuvant chemotherapy. SFRP1 may help guide the clinician and be a possible target for epigenetically modifying drugs.
目前用于胰腺腺癌（PDAC）的基于血液的预后生物标志物有限。最近，分泌型卷曲相关蛋白1（SFRP1）的启动子高甲基化（phSFRP1）与吉西他滨治疗的IV期PDAC患者的不良预后相关。本研究探讨phSFRP1在较低分期PDAC患者中的作用。
基于亚硫酸氢盐处理过程，用甲基化特异性PCR分析SFRP1基因的启动子区域。采用Kaplan-Meier曲线、对数秩检验和广义线性回归分析来评估12个月和24个月时的受限平均生存时间。
该研究纳入了211例I-II期PDAC患者。phSFRP1患者的中位总生存期为13.1个月，而SFRP1未甲基化（umSFRP1）患者为19.6个月。在调整分析中，phSFRP1分别与12个月和24个月时生命损失1.15个月（95%CI -2.11，-0.20）和2.71个月（95%CI -2.71，-0.45）相关。phSFRP1对无病生存期或无进展生存期无显著影响。在I-II期PDAC中，phSFRP1患者的预后比umSFRP1患者差。
结果可能表明预后不良可能是由于辅助化疗获益减少所致。SFRP1可能有助于指导临床医生，并且可能成为表观遗传修饰药物的靶点。
