Jafarnezhad-Ansariha Fahimeh, Contran Nicole, Cristofori Chiara, Simonato Manuela, Davanzo Veronica, Moz Stefania, Galozzi Paola, Fogar Paola, Nordi Evelyn, Padoan Andrea, Aita Ada, Fassan Matteo, Fantin Alberto, Sartori Anna, Sperti Cosimo, Correani Alessio, Carnielli Virgilio, Cogo Paola, Basso Daniela
Department of Surgery, Oncology and Gastroenterology-DISCOG, University of Padua, 35128 Padua, Italy.
Laboratory Medicine, University-Hospital of Padua, 35128 Padua, Italy.
Cancers (Basel). 2025 Feb 14;17(4):643. doi: 10.3390/cancers17040643.
Pancreatic cystic neoplasms (PCNs), particularly intraductal papillary mucinous neoplasms (IPMNs), present a challenge for their potential malignancy. Despite promising biomarkers like CEA, amylase, and glucose, our study investigates whether metabolic indices in blood and cystic fluids (CFs), in addition to lymphocyte subsets and hematopoietic stem/progenitor cells (HSPCs), can effectively differentiate between high- and low-risk PCNs. A total of 26 patients (11 males, mean age 69.5 ± 9 years) undergoing Endoscopic Ultrasound-guided Fine Needle Aspiration were consecutively enrolled. Analyses included blood, serum, and CF, assessing glucose, CEA, cholesterol (total, HDL, and LDL), and total proteins. Flow cytometry examined immunophenotyping in peripheral blood and cystic fluids. Mass spectrometry was used for the metabolomic analysis of CF. Sensitivity, specificity, and ROC analyses evaluated discriminatory power. A total of 25 out of 26 patients had IPMN. Patients were categorized as low or high risk based on multidisciplinary evaluation of clinical, radiological, and endoscopic data. High-risk patients showed lower CF total proteins and LDL cholesterol ( = 0.005 and = 0.031), with a marked reduction in CF lymphocytes ( = 0.005). HSCPs were absent in CF. In blood, high-risk patients showed increased non-MHC-restricted cytotoxic T cells ( = 0.019). The metabolomic analysis revealed significantly reduced middle and long-chain acyl carnitines (AcCa) and tryptophan metabolites in high-risk patients. ROC curves indicated comparable discriminant abilities for CF lymphocytes (AUC 0.868), CF total proteins (AUC 0.859), and CF LDL cholesterol (AUC 0.795). The highest performance was achieved by the AcCa 14:2 and 16:0 (AUC: 0.9221 and 0.8857, respectively). CF levels of glucose, CEA, LDL cholesterol, and total proteins together with lymphocyte counts are easy translational biomarkers that may support risk stratification of PCNs in IPMN patients and might be endorsed by metabolomic analysis. Further studies are required for potential clinical integration.
胰腺囊性肿瘤（PCNs），尤其是导管内乳头状黏液性肿瘤（IPMNs），因其潜在的恶性程度而构成挑战。尽管有癌胚抗原（CEA）、淀粉酶和葡萄糖等有前景的生物标志物，但我们的研究调查了血液和囊液（CFs）中的代谢指标，以及淋巴细胞亚群和造血干/祖细胞（HSPCs），是否能有效区分高风险和低风险的PCNs。共有26例接受内镜超声引导下细针穿刺的患者（11例男性，平均年龄69.5±9岁）连续入组。分析包括血液、血清和CF，评估葡萄糖、CEA、胆固醇（总胆固醇、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇）和总蛋白。流式细胞术检测外周血和囊液中的免疫表型。质谱用于CF的代谢组学分析。敏感性、特异性和受试者工作特征（ROC）分析评估判别能力。26例患者中有25例患有IPMN。根据临床、放射学和内镜数据的多学科评估，将患者分为低风险或高风险。高风险患者的CF总蛋白和低密度脂蛋白胆固醇较低（P = 0.005和P = 0.031），CF淋巴细胞显著减少（P = 0.005）。CF中不存在HSCPs。在血液中，高风险患者的非主要组织相容性复合体（MHC）限制性细胞毒性T细胞增加（P = 0.019）。代谢组学分析显示，高风险患者的中长链酰基肉碱（AcCa）和色氨酸代谢物显著减少。ROC曲线表明，CF淋巴细胞（曲线下面积[AUC] 0.868）、CF总蛋白（AUC 0.859）和CF低密度脂蛋白胆固醇（AUC 0.795）具有相当的判别能力。AcCa 14:2和16:0的表现最佳（AUC分别为0.9221和0.8857）。CF中的葡萄糖、CEA、低密度脂蛋白胆固醇和总蛋白水平以及淋巴细胞计数是易于转化的生物标志物，可能有助于IPMN患者PCNs的风险分层，并且可能得到代谢组学分析的支持。潜在的临床整合还需要进一步研究。
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