Li Pei, Shi Jian-Xiang, Xing Meng-Tao, Dai Li-Ping, Li Ji-Tian, Zhang Jian-Ying
1 The Academy of Medical Sciences, Zhengzhou University, Zhengzhou, China.
2 Department of Biological Sciences, The University of Texas at El Paso, El Paso, TX, USA.
Tumour Biol. 2017 Oct;39(10):1010428317711662. doi: 10.1177/1010428317711662.
We evaluated autoantibodies against nine tumor-associated antigens, including p62, p16, Koc, p53, Cyclin B1, Cyclin E, Survivin, HCC1, and RalA as serological markers in lung cancer. Enzyme-linked immunosorbent assay (ELISA) was used to detect autoantibodies in sera from 50 lung cancer patients and 42 normal controls. Then, four tumor-associated antigens of higher values were selected and validated in sera from validation group. Western blot and serum absorption test were used to confirm positive findings from ELISA. When cutoff values were set as mean optical density values plus 3 standard deviation of normal controls, the positive rate of autoantibodies against four tumor-associated antigens (Survivin, Cyclin B1, HCC1, and p53) reached 32%, 20%, 22%, and 18%, with area under the curve values of 0.653, 0.767, 0.622, and 0.623 in sera from 50 lung cancer, respectively (all p < 0.05). Results from the validation group confirmed the results. When lung cancer patients were divided by their clinicopathological characteristics into different subgroups, we have found that serum anti-Cyclin B1 and anti-HCC1 autoantibodies increased in stages 1, 2, and 3 lung cancer; anti-Survivin autoantibodies increased in stages 2 and 3 lung cancer; and anti-p53 autoantibody only increased in stage 1 when compared with their corresponding levels in controls (all p < 0.05). Serum anti-Cyclin B1 and anti-Survivin autoantibodies increased with disease histological grade 2 and 3 (both p < 0.05). And higher serum level of anti-p53 autoantibodies is positively associated with tumor size. Parallel utilization of these four anti-tumor-associated antigens (any positive) can increase sensitivity to 65.0% at 100% specificity with area under the curve of 0.908 ( p < 0.001) in lung cancer detection in validation group. Our results suggest that autoantibodies against these four tumor-associated antigens have higher values in lung cancer detection, and serum anti-Cyclin-B1 has the potential to serve as novel non-invasive biomarkers in early-stage lung cancer.
我们评估了针对九种肿瘤相关抗原（包括p62、p16、Koc、p53、细胞周期蛋白B1、细胞周期蛋白E、生存素、HCC1和RalA）的自身抗体，将其作为肺癌的血清学标志物。采用酶联免疫吸附测定（ELISA）法检测50例肺癌患者和42例正常对照者血清中的自身抗体。然后，选择四种自身抗体值较高的肿瘤相关抗原在验证组血清中进行验证。采用蛋白质印迹法和血清吸收试验来确认ELISA的阳性结果。当将临界值设定为正常对照者的平均光密度值加3个标准差时，针对四种肿瘤相关抗原（生存素、细胞周期蛋白B1、HCC1和p53）的自身抗体阳性率分别达到32%、20%、22%和18%，在50例肺癌患者血清中的曲线下面积值分别为0.653、0.767、0.622和0.623（均p<0.05）。验证组的结果证实了上述结果。当根据临床病理特征将肺癌患者分为不同亚组时，我们发现血清抗细胞周期蛋白B1和抗HCC1自身抗体在肺癌1、2和3期升高；抗生存素自身抗体在肺癌2和3期升高；与相应对照水平相比，抗p53自身抗体仅在1期升高（均p<0.05）。血清抗细胞周期蛋白B1和抗生存素自身抗体随疾病组织学分级2和3级升高（均p<0.05）。并且抗p53自身抗体的血清水平升高与肿瘤大小呈正相关。在验证组肺癌检测中，平行使用这四种抗肿瘤相关抗原（任何一项阳性）可在100%特异性时将敏感性提高到65.0%，曲线下面积为0.908（p<0.001）。我们的结果表明，针对这四种肿瘤相关抗原的自身抗体在肺癌检测中具有较高价值，血清抗细胞周期蛋白B1有潜力作为早期肺癌新型非侵入性生物标志物。
