Trembath Hannah E, LaBella Michelle E, Kearney Joseph F, Hariharan Arthi, Zarmer Sandra, Nabors Mariaelena, McCabe Ian, Zhao Ryan T, Meyers Michael, Kim Hong Jin, Yeh Jen Jen
Department of Surgery, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
J Surg Oncol. 2025 May;131(6):1134-1141. doi: 10.1002/jso.28044. Epub 2024 Dec 22.
Studies show that new onset diabetes mellitus (DM) (NOD) predates the diagnosis of PDAC by up to 2 years. Two tumor-intrinsic molecular subtypes of PDAC that are prognostic and predictive of chemotherapy response have been described and validated. We hypothesize that patients with NOD may have different molecular subtypes and prognoses.
This is a single-institution study of patients who underwent resection for PDAC from 2009 to 2022 with de-identified samples available for sequencing. Demographic and clinical factors were examined using bivariate and multivariate analysis.
A total of 97 patients met inclusion criteria: 70 with no history of DM, 11 with longstanding DM (> 2 years), and 16 with NOD. The demographics between groups were overall similar. After controlling for age, sex, race, BMI, and tobacco history, NOD was not a significant predictor of PDAC subtype. There were no survival differences between groups. Transcriptomic analysis suggests the upregulation of inflammatory and immune activation and regulation pathways in NOD.
As continued interest in NOD and PDAC mounts, we are the first to examine if NOD may be associated with molecular subtypes and outcomes. Further investigation into the underlying pathophysiology of the NOD group is still needed.
研究表明，新发糖尿病（DM）在胰腺癌（PDAC）诊断前出现的时间可达2年。已经描述并验证了两种具有预后意义且可预测化疗反应的胰腺癌肿瘤内在分子亚型。我们假设新发糖尿病患者可能具有不同的分子亚型和预后。
这是一项单机构研究，研究对象为2009年至2022年接受胰腺癌切除术的患者，其去识别化样本可用于测序。使用双变量和多变量分析检查人口统计学和临床因素。
共有97名患者符合纳入标准：70名无糖尿病病史，11名患有长期糖尿病（>2年），16名患有新发糖尿病。各组之间的人口统计学总体相似。在控制年龄、性别、种族、体重指数和吸烟史后，新发糖尿病不是胰腺癌亚型的显著预测因素。各组之间无生存差异。转录组分析表明，新发糖尿病中炎症和免疫激活及调节途径上调。
随着对新发糖尿病和胰腺癌的持续关注增加，我们首次研究新发糖尿病是否可能与分子亚型和预后相关。仍需要对新发糖尿病组的潜在病理生理学进行进一步研究。
