Zhong Ailing, Qin Ruihuan, Qin Wenjun, Han Jing, Gu Yong, Zhou Lei, Zhang Hongqin, Ren Shifang, Lu Renquan, Guo Lin, Gu Jianxin
Department of Clinical Laboratory, Shanghai Cancer Center, Fudan University, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Front Oncol. 2019 Feb 27;9:114. doi: 10.3389/fonc.2019.00114. eCollection 2019.
Although Carbohydrate antigen 19-9 (CA19-9) is considered clinically useful and informative for pancreatic carcinoma (PC), false positive results, and false negative results have restricted its clinical use. Especially missed or delayed diagnosis of PC patients with negative CA19-9 value limited the utility. To improve prognosis of PC patients, the discovery of reliable biomarkers to assist CA19-9 is desired. Serum IgG galactosylation based on our previous report was altered in PC patients comparing to healthy controls. The objective of this study was to explore the diagnostic significance of IgG galactosylation in assisting CA19-9 for PC in a comprehensive way. Serum IgG galactosylation profiles were analyzed by MALDI-MS in cohort 1 ( = 252) and cohort 2 in which all CA19-9 levels were negative ( = 133). In each cohort, not only healthy controls and PC patients but also benign pancreatic disease (BPD) patients were enrolled. Peaks were acquired by the software of MALDI-MS sample acquisition, followed by being processed and analyzed by the software of Progenesis MALDI. IgG Gal-ratio, which was calculated from the relative intensity of peaks G0, G1, and G2 according to the formula (G0/(G1+G2×2)), was employed as an index for indicating the distribution of IgG galactosylation. The Gal-ratio was elevated in PC comparing with that in non-cancer group (healthy controls and BPD). The area under the receiver operating characteristic curve (AUC) of IgG Gal-ratio was higher than that of CA19-9 (0.912 vs. 0.814). The performance was further improved when Gal-ratio and CA19-9 were combined (AUC: 0.928). Meanwhile, Gal-ratio also had great diagnostic value with a sensitivity of 92.31% (AUC: 0.883) in detection of PC at early stage. Notably, IgG Gal-ratio has great sensitivity (90.63%) and specificity (76.81%) in CA19-9-negative PC patients. IgG Gal-ratio had a great performance in detection of PC and could be used to assist CA19-9 in improving diagnosis performance through early stage detection, differentiation from BPD, and PC diagnosis with CA19-9-negative level.
尽管碳水化合物抗原19-9（CA19-9）在胰腺癌（PC）的临床诊断中被认为是有用且信息丰富的，但假阳性和假阴性结果限制了其临床应用。特别是CA19-9值为阴性的PC患者的漏诊或延迟诊断限制了其效用。为了改善PC患者的预后，需要发现可靠的生物标志物来辅助CA19-9。根据我们之前的报告，与健康对照相比，PC患者血清IgG半乳糖基化发生了改变。本研究的目的是以综合方式探讨IgG半乳糖基化在辅助CA19-9诊断PC中的意义。在队列1（n = 252）和队列2（所有CA19-9水平均为阴性，n = 133）中，通过基质辅助激光解吸电离质谱（MALDI-MS）分析血清IgG半乳糖基化谱。在每个队列中，不仅纳入了健康对照和PC患者，还纳入了良性胰腺疾病（BPD）患者。通过MALDI-MS样本采集软件获取峰，然后由Progenesis MALDI软件进行处理和分析。根据公式（G0/(G1+G2×2)）从峰G0、G1和G2的相对强度计算得出的IgG Gal-比值，用作指示IgG半乳糖基化分布的指标。与非癌症组（健康对照和BPD）相比，PC患者的Gal-比值升高。IgG Gal-比值的受试者工作特征曲线下面积（AUC）高于CA19-9（0.912对0.814）。当Gal-比值和CA19-9联合使用时，性能进一步提高（AUC：0.928）。同时，Gal-比值在早期PC检测中也具有很高的诊断价值，敏感性为92.31%（AUC：0.883）。值得注意的是，IgG Gal-比值在CA19-9阴性的PC患者中具有很高的敏感性（90.63%）和特异性（76.81%）。IgG Gal-比值在PC检测中表现出色，可用于辅助CA19-9通过早期检测、与BPD鉴别以及CA19-9阴性水平的PC诊断来提高诊断性能。
