背景:由于缺乏敏感的液体活检方法和有效的生物标志物,胰腺癌(PC)的早期诊断极其困难。我们试图评估循环炎症标志物是否可以补充CA199以检测早期PC。
方法:我们招募了430例早期PC患者,287例其他胰腺肿瘤(OPT),和401个健康对照(HC)。将患者和HC随机分为训练集(n=872)和两个测试集(n1=218,n2=28)。研究受试者工作特征(ROC)曲线以评估循环炎症标志物比率的诊断性能,CA199,以及训练集中标记比率的组合,然后将在两个测试集中进行验证。
结果:循环纤维蛋白原,中性粒细胞,和单核细胞在PC患者中明显更高,而循环白蛋白,前白蛋白,淋巴细胞,与HC和OPT相比,PC患者的血小板明显降低(均P<0.05)。纤维蛋白原至白蛋白(FAR),纤维蛋白原-前白蛋白(FPR),中性粒细胞对淋巴细胞(NLR),血小板淋巴细胞(PLR),单核细胞对淋巴细胞(MLR),与HC和OPT患者相比,PC患者的纤维蛋白原与淋巴细胞(FLR)比率明显更高,而预后营养指数值(PNI)则更低(均P<0.05)。结合FAR,FPR,CA199和FLR在区分早期PC患者和HC患者方面表现出最佳诊断价值,曲线下面积(AUC)为0.964,在训练集中区分早期PC患者和OPT患者的AUC为0.924。在测试集中,与HC相比,当比较PC与OPT时,组合标志物对PC具有强大的效率,AUC为0.947和AUC0.942.CA199、FAR、FPR,和FLR用于区分胰头癌(PHC)和其他胰头肿瘤(OPHT)患者,和0.894用于区分胰腺体尾癌(PBTC)和其他胰腺体尾癌(OPBTT)患者。
结论:FAR的组合,FPR,FLR,CA199可以作为一种潜在的非侵入性生物标志物,用于区分早期PC与HC和OPT,尤其是早期PHC.
BACKGROUND: An early diagnosis of pancreatic cancer (PC) is extremely difficult because of the lack of sensitive liquid biopsy methods and effective biomarkers. We attempted to evaluate whether circulating inflammatory marker could complement CA199 for the detection of early-stage PC.
METHODS: We enrolled 430 patients with early-stage PC, 287 patients with other pancreatic tumors (OPT), and 401 healthy controls (HC). The patients and HC were randomly divided into a training set (n = 872) and two testing sets (n1 = 218, n2 = 28). The receiver operating characteristic (ROC) curves were investigated to evaluate the diagnostic performance of circulating inflammatory markers ratios, CA199, and combinations of the markers ratios in the training set, which would then be validated in the two testing sets.
RESULTS: Circulating fibrinogen, neutrophils, and monocytes in patients with PC were significantly higher while circulating albumin, prealbumin, lymphocytes, and platelets of patients with PC were significantly lower compared to those of HC and OPT (all P < 0.05). The fibrinogen-to-albumin (
FAR), fibrinogen-to-prealbumin (FPR), neutrophil-to-lymphocyte (NLR), platelet-to-lymphocyte (PLR), monocyte-to-lymphocyte (MLR), and fibrinogen-to-lymphocyte (FLR) ratios were significantly higher while the prognostic nutrition index values (PNI) were lower in patients with PC than in HC and OPT (all P < 0.05). Combining the
FAR, FPR, and FLR with CA199 exhibited the best diagnostic value for distinguishing patients with early-stage PC from HC with an area under the curve (AUC) of 0.964, and for distinguishing patients with early-stage PC from OPT with an AUC of 0.924 in the training sets. In the testing set, compared with HC, the combination markers had powerful efficiency for PC with an AUC 0.947 and AUC 0.942 when comparing PC with OPT. The AUC was 0.915 for the combination of CA199,
FAR, FPR, and FLR for differentiating between patients with pancreatic head cancer (PHC) and other pancreatic head tumors (OPHT), and 0.894 for differentiating between patients with pancreatic body and tail cancer (PBTC) and other pancreatic body and tail tumors (OPBTT).
CONCLUSIONS: A combination of
FAR, FPR, FLR, and CA199 may serve as a potential non-invasive biomarker for differentiating early-stage PC from HC and OPT, especially early-stage PHC.