Chun Jung Won, Lee Dong-Eun, Han Nayoung, Heo SooBeen, Kim Hyeji, Lee Mi Rim, Park Hyeong Min, Han Sung-Sik, Park Sang-Jae, Kim Tae Hyun, Lee Woo Jin, Kim Yun-Hee, Kong Sun-Young, Woo Sang Myung
Center for Liver and Pancreatobiliary Cancer, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si 10408, Republic of Korea.
Research Institute, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si 10408, Republic of Korea.
Cancers (Basel). 2025 Mar 5;17(5):896. doi: 10.3390/cancers17050896.
Several pancreatic adenocarcinoma (PA) biomarkers beyond the traditional carbohydrate antigen (CA)19-9 have been identified but are lacking large-scale prospective validation. This prospective cohort study evaluated the prognostic impact of potential PA biomarkers.
We enrolled 238 of 288 patients with histologically proven PA. We assessed candidate biomarkers, including CA19-9, germline , and mutations, as well as mutant circulating tumor DNA (ctDNA) in blood samples. Additionally, we evaluated the expression of SLC29A1 (hENT1), DCK, CES2, and GATA6. We examined the association of candidate biomarkers with progression-free survival (PFS) and overall survival (OS).
We analyzed biomarker efficacy in 200 (median age 65 years; 55% male) of the enrolled patients who received chemotherapy. A high mutant ctDNA concentration (hazard ratio [HR]: 1.508 and 95% confidence interval [CI]: 1.052-2.161 for PFS; HR: 1.796 and 95% CI: 1.203-2.681 for OS) and high CA19-9 level (HR: 1.647 and 95% CI: 1.177-2.306 for PFS; HR: 1.803 and 95% CI: 1.248-2.605 for OS) were associated with poor prognosis. High GATA6 RNA expression was linked to longer PFS (HR: 0.336 and 95% CI: 0.195-0.582) and OS (HR: 0.304 and 95% CI: 0.165-0.560).
Plasma mutant ctDNA concentrations and GATA6 expression could serve as significant prognostic biomarkers in patients with PA, potentially guiding therapeutic decisions and prognostication.
除了传统的糖类抗原（CA）19-9外，已经鉴定出几种胰腺腺癌（PA）生物标志物，但缺乏大规模前瞻性验证。这项前瞻性队列研究评估了潜在PA生物标志物的预后影响。
我们从288例经组织学证实为PA的患者中纳入了238例。我们评估了候选生物标志物，包括CA19-9、种系和突变，以及血液样本中的突变循环肿瘤DNA（ctDNA）。此外，我们评估了SLC29A1（hENT1）、DCK、CES2和GATA6的表达。我们研究了候选生物标志物与无进展生存期（PFS）和总生存期（OS）的关联。
我们分析了200例（中位年龄65岁；55%为男性）接受化疗的入组患者的生物标志物疗效。高突变ctDNA浓度（PFS的风险比[HR]：1.508，95%置信区间[CI]：1.052-2.161；OS的HR：1.796，95%CI：1.203-2.681）和高CA19-9水平（PFS的HR：1.647，95%CI：1.177-2.306；OS的HR：1.803，95%CI：1.248-2.605）与预后不良相关。高GATA6 RNA表达与更长的PFS（HR：0.336，95%CI：0.195-0.582）和OS（HR：0.304，95%CI：0.165-0.560）相关。
血浆突变ctDNA浓度和GATA6表达可作为PA患者重要的预后生物标志物，可能指导治疗决策和预后评估。
