生长分化因子(GDF-15)浓度联合血清Ca125水平在胰腺肿块分化方面优于常用的癌症生物标志物。

IF 1.9
Piotr Hogendorf, Adam Durczyński, Aleksander Skulimowski, Anna Kumor, Grażyna Poznańska, Janusz Strzelczyk
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引用次数: 22

摘要

背景:根据目前的估计,到2020年胰腺癌(PDAC)将成为美国第二大癌症相关死亡。它的晚期表现和缺乏良好的早期检测方法是生存率极低的原因。因此,迫切需要开发高灵敏度和特异性的标记物。GDF-15是TGFbeta家族的一员,近年来作为一种在多种肿瘤的癌变中起重要作用的蛋白被发现。目的:我们的目的是评估GDF-15、IL-17、IL-23血清浓度和PDAC标志物在胰腺腺癌与慢性胰腺炎鉴别中的潜力。方法:对63例连续行胰胆管病变手术的患者进行研究。采用标准实验室方案评估CEA、CA125和Ca19-9水平。术前经中央静脉导管采集血清样本。采用ELISA试剂盒检测GDF-15、Il-17、Il-23水平。对手术标本进行标准病理检查后,将患者分为胰腺腺癌组42例,局灶性慢性胰腺炎组21例。结果:CP和PDAC患者的平均GDF-15浓度分别为2247.95(±179.27)和7694.58(±1878.94)[pg/mL] (p= 0.011)。CP和PDAC患者Il-17、Il-23、Ca19-9、Ca125、Ca15-3、CEA的平均浓度分别为862.36(±30.84)和841.83(±33.94),p= 0.833;127.85(±5.87)vs 127.51(±9.74)p= 0.175;34.95(±23.34)vs 266.62(±49.7)p= 0.001;13.4(±1.6)vs 39.27(±6.85)p= 0.005;18.4(±1.48)vs 20.2(±1.38)p= 0.416;1.96(±0.38)vs 5.93(±1.74)p= 0.004。为了将这些标记与常规使用的标记进行比较,我们建立了ROC曲线。CA19-9临床使用的截断点为大于或等于36 IU/mL,特异性为90.5%,敏感性为57.14%。同时,GDF-15的特异性为76.19%,敏感性为73.8%,最佳临界值为2.7 ng/mL。虽然在我们的研究组中CA19-9具有出色的特异性,但其低灵敏度阻碍了其实用性。另一方面,GDF-15参数平衡良好,使其成为更有用的PDAC生物标志物。结论:GDF-15在鉴别慢性胰腺炎胰腺肿块与胰腺腺癌方面比Ca19-9更准确。白细胞介素17和23不能被认为是PDAC的生物标志物。血清GDF-15浓度应进一步研究,以评估其在胰腺腺癌诊断中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Growth differentiation factor (GDF-15) concentration combined with Ca125 levels in serum is superior to commonly used cancer biomarkers in differentiation of pancreatic mass.

Background: Pancreatic cancer (PDAC) will have been the second leading cancer-related death in the United States by 2020, according to current estimation. Its late manifestation and the lack of good early detection methods are the cause of extremely low survival rates. Therefore, there is an urgent need to develop highly sensitive and specific marker. GDF-15, a member of TGFbeta family, has recently emerged as a protein playing an important role in carcinogenesis of various neoplasms.

Objective: Our aim was to assess the potential of GDF-15, IL-17, IL-23 serum concentration, and the panel of PDAC markers in differentiating pancreatic adenocarcinoma from chronic pancreatitis.

Methods: Sixty-three consecutive patients operated on due to pancreatobiliary lesions were enrolled in this study. Levels of CEA, CA125 and Ca19-9 were assessed using standard laboratory protocols. A sample of serum was collected prior to the surgery via central line. Levels of GDF-15, Il-17, Il-23 were measured using a ELISA kit. After standard pathological examination of specimens obtained on surgery, patients were divided into 2 groups: 42 patients with pancreatic adenocarcinoma and 21 patients with focal chronic pancreatitis.

Results: Mean GDF-15 concentration in patients with CP vs PDAC was 2247.95 (± 179.27) vs 7694.58 (± 1878.94) [pg/mL] respectively (p= 0.011). Mean concentration of Il-17, Il-23, Ca19-9, Ca125, Ca15-3, CEA in patients with CP and PDAC was 862.36 (± 30.84) vs 841.83 (± 33.94) p= 0.833; 127.85 (± 5.87) vs 127.51 (± 9.74) p= 0.175; 34.95 (± 23.34) vs 266.62 (± 49.7) p= 0.001; 13.4 (± 1.6) vs 39.27 (± 6.85) p= 0.005; 18.4 (± 1.48) vs 20.2 (± 1.38) p= 0.416; 1.96 (± 0.38) vs 5.93 (± 1.74) p= 0.004 respectively. In order to compare these markers with the routinely used ones, ROC curve was built. CA19-9 with clinically used cut-off point of ⩾ 36 IU/mL has specificity of 90.5% and sensitivity of 57.14%. At the same time GDF-15 with the optimal cut-off point of 2.7 ng/mL has specificity of 76.19% and sensitivity of 73.8%. Although in our research group CA19-9 has an excellent specificity, its usefulness is hampered by its low sensitivity. On the other hand, GDF-15 parameters are well-balanced making it a more useful biomarker of PDAC.

Conclusions: In conclusion, GDF-15 is more accurate than Ca19-9 in differentiating pancreatic mass due to chronic pancreatitis from pancreatic adenocarcinoma. Interleukin 17 and 23 cannot be considered as PDAC biomarkers. GDF-15 concentration in serum should be further investigated in order to assess their usefulness in pancreatic adenocarcinoma diagnosis.

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