Department of General and Transplant Surgery, Medical University of Lodz, Poland.
Department of Pulmonology and Allergy, Medical University of Lodz, Poland.
Cancer Biomark. 2018 Feb 14;21(3):505-511. doi: 10.3233/CBM-170203.
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.
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.
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.
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.
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.
根据目前的估计，到 2020 年，胰腺癌（PDAC）将成为美国第二大与癌症相关的死亡原因。其晚期表现和缺乏良好的早期检测方法是极低生存率的原因。因此，迫切需要开发高度敏感和特异的标志物。GDF-15，TGFbeta 家族的一个成员，最近作为各种肿瘤发生中起重要作用的蛋白质出现。
我们的目的是评估 GDF-15、IL-17、IL-23 血清浓度和 PDAC 标志物组合在鉴别胰腺腺癌与慢性胰腺炎中的潜力。
本研究纳入了 63 例因胆胰病变而行手术的连续患者。采用标准实验室方法评估 CEA、CA125 和 Ca19-9 的水平。通过中心静脉在手术前采集血清样本。使用 ELISA 试剂盒测量 GDF-15、Il-17、Il-23 的水平。在手术标本进行标准病理检查后，将患者分为 2 组：42 例胰腺腺癌患者和 21 例局灶性慢性胰腺炎患者。
CP 组与 PDAC 组的平均 GDF-15 浓度分别为 2247.95（±179.27）和 7694.58（±1878.94）[pg/mL]（p=0.011）。CP 和 PDAC 患者的 Il-17、Il-23、Ca19-9、Ca125、Ca15-3、CEA 平均浓度分别为 862.36（±30.84）和 841.83（±33.94）（p=0.833）；127.85（±5.87）和 127.51（±9.74）（p=0.175）；34.95（±23.34）和 266.62（±49.7）（p=0.001）；13.4（±1.6）和 39.27（±6.85）（p=0.005）；18.4（±1.48）和 20.2（±1.38）（p=0.416）；1.96（±0.38）和 5.93（±1.74）（p=0.004）。为了将这些标志物与常规使用的标志物进行比较，绘制了 ROC 曲线。CA19-9 采用临床使用的 ⩾36IU/mL 切点，特异性为 90.5%，灵敏度为 57.14%。同时，GDF-15 采用最佳切点 2.7ng/mL，特异性为 76.19%，灵敏度为 73.8%。尽管在我们的研究组中，CA19-9 具有极好的特异性，但由于其灵敏度低，其用途受到限制。另一方面，GDF-15 具有良好的均衡参数，使其成为更有用的 PDAC 生物标志物。
总之，GDF-15 在鉴别因慢性胰腺炎引起的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 不能作为 PDAC 标志物。应进一步研究血清中 GDF-15 浓度，以评估其在胰腺腺癌诊断中的有用性。
