Dataset related to article "Metabolome of Pancreatic Juice Delineates Distinct Clinical Profiles of Pancreatic Cancer and Reveals a Link between Glucose Metabolism and PD-1+ Cells"

This record contains data related to the article "Metabolome of Pancreatic Juice Delineates Distinct Clinical Profiles of Pancreatic Cancer and Reveals a Link between Glucose Metabolism and PD-1+ Cells". Better understanding of pancreatic diseases, including pancreatic ductal adenocarcinoma (PDAC), is an urgent medical need, with little advances in preoperative differential diagnosis, preventing rational selection of therapeutic strategies. The clinical management of pancreatic cancer patients would benefit from the identification of variables distinctively associated with the multiplicity of pancre- atic disorders. We investigated, by 1H nuclear magnetic resonance, the metabolomic fingerprint of pancreatic juice (the biofluid that collects pancreatic products) in 40 patients with different pancreatic diseases. Metabolic variables discriminated PDAC from other less aggressive pancreatic diseases and identified metabolic clusters of patients with distinct clinical behaviors. PDAC specimens were overtly glycolytic, with significant accumulation of lactate, which was probed as a disease-specific variable in pancreatic juice from a larger cohort of 106 patients. In human PDAC sections, high expression of the glucose transporter GLUT-1 correlated with tumor grade and a higher density of PD-1+ T cells, suggesting their accumulation in glycolytic tumors. In a preclinical model, PD-1+ CD8 tumor–infiltrating lymphocytes differentially infiltrat- ed PDAC tumors obtained from cell lines with different metabolic consumption, and tumors metabolically rewired by knocking down the phosphofructokinase (Pfkm) gene displayed a decrease in PD-1+ cell infiltration. Collectively, we introduced pancreatic juice as a valuable source of metabolic variables that could contri- bute to differential diagnosis. The correlation of metabolic markers with immune infiltration suggests that upfront evaluation of the metabolic profile of PDAC patients could foster the introduction of immunotherapeutic approaches for pancreatic cancer.本数据集关联论文《胰液代谢组学勾勒胰腺癌差异化临床表型并揭示糖代谢与PD-1阳性细胞的关联》。当前，针对包括胰腺导管腺癌（pancreatic ductal adenocarcinoma, PDAC）在内的胰腺疾病的认知仍存在显著短板，术前鉴别诊断领域进展缓慢，难以实现治疗策略的合理化选择，这已成为亟待解决的临床刚需。胰腺癌患者的临床管理亟需筛选出与多种胰腺疾病特异性相关的变量指标。本研究采用1H核磁共振（1H nuclear magnetic resonance）技术，对40例罹患不同胰腺疾病的患者的胰液——一种收集胰腺分泌物的生物体液——开展代谢组学指纹图谱分析。结果显示，代谢变量可有效区分胰腺导管腺癌与其他侵袭性更低的胰腺疾病，并可识别出具有独特临床行为特征的患者代谢聚类亚型。胰腺导管腺癌组织呈现显著的糖酵解表型，伴随乳酸大量积累；针对106例患者的更大队列分析证实，胰液中的乳酸可作为疾病特异性标志物。在人体胰腺导管腺癌组织切片中，葡萄糖转运蛋白GLUT-1的高表达与肿瘤分级及PD-1阳性T细胞的高密度呈正相关，提示糖酵解肿瘤中存在此类免疫细胞的聚集。在临床前模型中，PD-1阳性CD8+肿瘤浸润淋巴细胞对不同代谢消耗特性的胰腺导管腺癌异种移植瘤的浸润程度存在显著差异；通过敲低磷酸果糖激酶（phosphofructokinase, Pfkm）基因重塑肿瘤代谢表型后，PD-1阳性细胞的浸润水平显著降低。综上，本研究证实胰液可作为代谢变量的可靠来源，有望为胰腺癌的鉴别诊断提供支持。代谢标志物与肿瘤免疫浸润的相关性提示，对胰腺导管腺癌患者的代谢谱进行术前评估，有望推动胰腺癌免疫治疗策略的临床转化与应用。