OBJECTIVES The purpose of this study is to discover novel tumor-associated antigens (TAAs) to improve the diagnosis of lung cancer (LC). MATERIALS AND METHODS Oncomine database was used to discover potential TAAs from LC tissues, enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of autoantibodies against TAAs in two independent sets (identification set, n = 368; validation set, n = 1011). RESULTS Analyses of sera from identification set showed that the sensitivity of autoantibodies against five TAAs (HMGB3, ZWINT, GREM1, NUSAP1 and MMP12) reached 57.1%, 42.4%, 38.0%, 36.4% and 20.7%, with area under ROC curve (AUC) of 0.85, 0.75, 0.71, 0.73 and 0.70, respectively. It also validated the diagnostic performances of these autoantibodies with AUC of 0.72, 0.65, 0.61, 0.64 and 0.64, respectively. Autoantibody against HMGB3 exhibited significantly increased frequency in early LC (53.3%) compared to advanced LC (29.3%) (P < .05). The positive rates of autoantibody against HMGB3 and NUSAP1 in serum of LC patients without distant metastasis were significantly higher than that of distant metastatic LC (P < .05). When each of the three protein biomarkers (CEA, CA125 and CYFRA21-1) was combined with anti-HMGB3 autoantibody, the sensitivity of early LC increased to 72.7%, 63.3% and 75.9% from 36.4%, 13.3% and 27.6%, respectively. CONCLUSION Autoantibodies against 5 TAAs (HMGB3, ZWINT, GREM1, NUSAP1 and MMP12) might have favorable diagnostic values in LC detection, and autoantibody against HMGB3 has the potential to serve as a serological biomarker in early-stage LC. The combination of protein biomarkers and anti-HMGB3 might contribute to detection of early-stage LC.

中文翻译：

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基于Oncomine数据库的肿瘤相关抗原的筛选以及自身抗体在肺癌中的诊断价值。

目的本研究的目的是发现新型肿瘤相关抗原（TAA）以改善肺癌（LC）的诊断。材料和方法使用Oncomine数据库从LC组织中发现潜在的TAA，使用酶联免疫吸附测定（ELISA）检测两组独立的针对TAA的自身抗体水平（鉴定组，n = 368；验证组，n = 1011）。结果通过鉴定集进行的血清分析表明，针对五个TAA（HMGB3，ZWINT，GREM1，NUSAP1和MMP12）的自身抗体的敏感性分别达到57.1％，42.4％，38.0％，36.4％和20.7％，ROC曲线下的面积（AUC） ）分别为0.85、0.75、0.71、0.73和0.70。它还验证了这些自身抗体的诊断性能，AUC分别为0.72、0.65、0.61、0.64和0.64。与晚期LC（29.3％）相比，针对HMGB3的自身抗体在早期LC（53.3％）中表现出明显增加的频率（P <.05）。无远处转移的LC患者血清中针对HMGB3和NUSAP1的自身抗体阳性率显着高于远处转移LC（P <.05）。当将三种蛋白质生物标志物（CEA，CA125和CYFRA21-1）分别与抗HMGB3自身抗体结合使用时，早期LC的敏感性分别从36.4％，13.3％和27.6％提高到72.7％，63.3％和75.9％。 。结论针对5种TAA的自身抗体（HMGB3，ZWINT，GREM1，NUSAP1和MMP12）在LC检测中可能具有良好的诊断价值，而针对HMGB3的自身抗体具有在早期LC中作为血清生物标志物的潜力。