Natural Product Research Institute, College of Pharmacy, Seoul National University, Seoul, Korea.
Department of Biomedical Sciences, College of Medicine, and Program in Biomedical Science and Engineering, Inha University, Incheon, Korea.
J Natl Cancer Inst. 2022 Feb 7;114(2):228-234. doi: 10.1093/jnci/djab191.
Pancreatic cancer (PC) has a grim prognosis, and an early diagnostic biomarker has been highly desired. The molecular link between diabetes and PC has not been well established.
Bioinformatics screening was performed for a serum PC marker. Experiments in cell lines (5 PC and 1 normal cell lines), mouse models, and human tissue staining (37 PC and 10 normal cases) were performed to test asprosin production from PC. Asprosin's diagnostic performance was tested with serums from multi-center cohorts (347 PC, 209 normal, and 55 additional diabetic patients) and evaluated according to PC status, stages, and diabetic status, which was compared with that of CA19-9.
Asprosin, a diabetes-related hormone, was found from the bioinformatics screening, and its production from PC was confirmed. Serum asprosin levels from multi-center cohorts yielded an age-adjusted diagnostic area under the curve (AUC) of 0.987 (95% confidence interval [CI] = 0.961 to 0.997), superior to that of CA19-9 (AUC = 0.876, 95% CI = 0.847 to 0.905), and a cut-off of 7.18 ng/mL, at which the validation set exhibited a sensitivity of 0.957 and a specificity of 0.924. Importantly, the performance was maintained in early-stage and non-metastatic PC, consistent with the tissue staining. A slightly lower performance against additional diabetic patients (n = 55) was restored by combining asprosin and CA19-9 (AUC = 0.985, 95% CI = 0.975 to 0.995).
Asprosin is presented as an early-stage PC serum marker that may provide clues for PC-induced diabetes. Larger prospective clinical studies are warranted to solidify its utility.
胰腺癌（PC）预后较差，人们一直高度期望能发现一种早期诊断的生物标志物。糖尿病和 PC 之间的分子联系尚未得到很好的确立。
通过生物信息学筛选，寻找血清 PC 标志物。在细胞系（5 个 PC 细胞系和 1 个正常细胞系）、小鼠模型和人组织染色（37 个 PC 病例和 10 个正常病例）中进行实验，检测 PC 细胞产生的脯氨酸。通过多中心队列的血清样本（347 个 PC 病例、209 个正常对照和 55 个额外的糖尿病患者）检测脯氨酸的诊断性能，并根据 PC 状态、分期和糖尿病状态进行评估，与 CA19-9 进行比较。
从生物信息学筛选中发现了一种与糖尿病相关的激素——脯氨酸，且证实其可由 PC 产生。多中心队列的血清脯氨酸水平得出的年龄校正曲线下面积（AUC）为 0.987（95%置信区间 [CI] = 0.961 至 0.997），优于 CA19-9（AUC = 0.876，95% CI = 0.847 至 0.905），截断值为 7.18 ng/mL，验证集的灵敏度为 0.957，特异性为 0.924。重要的是，在早期和非转移性 PC 中，该表现与组织染色一致。通过将脯氨酸和 CA19-9 联合使用（AUC = 0.985，95% CI = 0.975 至 0.995），可以恢复对 55 例额外糖尿病患者（n = 55）稍低的性能。
脯氨酸是一种早期 PC 血清标志物，可能为 PC 诱导的糖尿病提供线索。需要更大规模的前瞻性临床研究来证实其应用价值。
