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文章:

囊液总蛋白、低密度脂蛋白胆固醇、脂质代谢物及淋巴细胞:导管内乳头状黏液性肿瘤的潜在警示性生物标志物

Cystic Fluid Total Proteins, Low-Density Lipoprotein Cholesterol, Lipid Metabolites, and Lymphocytes: Worrisome Biomarkers for Intraductal Papillary Mucinous Neoplasms

原文发布日期:14 February 2025

DOI: 10.3390/cancers17040643

类型: Article

开放获取: 是

 

英文摘要:

Objectives: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.Materials and Methods: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.Results: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 (p= 0.005 andp= 0.031), with a marked reduction in CF lymphocytes (p= 0.005). HSCPs were absent in CF. In blood, high-risk patients showed increased non-MHC-restricted cytotoxic T cells (p= 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).Conclusions: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.

 

摘要翻译: 

目的:胰腺囊性肿瘤(PCNs),尤其是导管内乳头状黏液性肿瘤(IPMNs),因其潜在的恶性风险而构成临床挑战。尽管CEA、淀粉酶和葡萄糖等生物标志物显示出潜力,本研究旨在探讨血液及囊液中的代谢指标,连同淋巴细胞亚群及造血干/祖细胞(HSPCs),是否能有效区分高危及低危PCNs。 材料与方法:连续纳入26例接受超声内镜引导下细针穿刺的患者(男性11例,平均年龄69.5±9岁)。检测分析涵盖血液、血清及囊液,评估指标包括葡萄糖、CEA、胆固醇(总胆固醇、高密度脂蛋白及低密度脂蛋白)和总蛋白。采用流式细胞术对外周血及囊液进行免疫表型分析,并运用质谱技术进行囊液代谢组学分析。通过敏感性、特异性及ROC分析评估各指标的鉴别效能。 结果:26例患者中25例为IPMN。根据临床、影像学及内镜资料的多学科综合评估,患者被分为低危组和高危组。高危组患者囊液总蛋白及低密度脂蛋白胆固醇水平显著降低(p=0.005和p=0.031),且囊液淋巴细胞数量明显减少(p=0.005)。囊液中未检出HSPCs。血液分析显示高危组患者非MHC限制性细胞毒性T细胞增多(p=0.019)。代谢组学分析揭示高危组患者中长链酰基肉碱(AcCa)及色氨酸代谢物显著降低。ROC曲线显示囊液淋巴细胞(AUC 0.868)、囊液总蛋白(AUC 0.859)及囊液低密度脂蛋白胆固醇(AUC 0.795)具有相近的鉴别能力,其中AcCa 14:2与16:0表现最佳(AUC分别为0.9221和0.8857)。 结论:囊液中葡萄糖、CEA、低密度脂蛋白胆固醇、总蛋白水平及淋巴细胞计数是易于转化的生物标志物,可辅助IPMN患者的PCNs风险分层,且该结果得到代谢组学分析的支持。未来需进一步研究以推动其临床转化应用。

 

原文链接:

Cystic Fluid Total Proteins, Low-Density Lipoprotein Cholesterol, Lipid Metabolites, and Lymphocytes: Worrisome Biomarkers for Intraductal Papillary Mucinous Neoplasms

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