开发一组血清 IgG 和 IgA 自身抗体用于结肠癌的早期诊断。
Development of a panel of serum IgG and IgA autoantibodies for early diagnosis of colon cancer.
机构信息
Provincial Clinical College, Fujian Medical University, Fuzhou 350001, China.
Department of Clinical Laboratory, Fujian Provincial Hospital Jinshan Branch, Fuzhou 350001, China.
出版信息
Int J Med Sci. 2020 Sep 25;17(17):2744-2750. doi: 10.7150/ijms.50169. eCollection 2020.
Our pilot study in a small cohort by ELISA showed that the levels and positive rates of serum IgG autoantibodies against p53, HRAS and NSG1, and IgA autoantibody against TIF1γ in early colon cancer (CC) group were significantly higher than that of colon benign lesion (CBL) group / healthy control (HC) group ( <0.01), which suggested that four autoantibodies might be valuable for the diagnosis of patients with CC at early stage. On the basis of pilot study, we intend to comprehensively elucidate the performance of four autoantibodies for the early diagnosis of CC in a large sample cohort, and explore the optimal panel of autoantibodies in the diagnosis of patients with CC at early stage. Western blot was used to define the ELISA results of serum anti-p53, HRAS, NSG1-IgG and anti-TIF1γ-IgA. The performances of anti-p53, HRAS, NSG1-IgG and anti-TIF1γ-IgA were evaluated by ELISA for the early diagnosis of CC with 601 serum samples of 157 patients with CC at early stage, 144 patients with CC at advanced stage, 130 patients with CBL, and 170 HC, and then the performances of different combinations of four autoantibodies were analyzed for the development of an optimal panel for the early diagnosis of CC. The results of anti-p53, HRAS, NSG1-IgG and anti-TIF1γ-IgA in western blotting were consistent with that in ELISA. The levels and positive rates of anti-p53, HRAS, NSG1-IgG and anti-TIF1γ-IgA in early CC group were significantly higher than that in CBL group/HC group ( <0.01), while had no significant difference from that in advanced CC group ( >0.05), of which anti-TIF1γ-IgA showed the highest area under the receiver operating characteristic curve (AUC) of 0.716 for the patients with CC at early stage, with 25.5% sensitivity and specificity at 96.7%. Additionally, a panel of anti-p53, HRAS-IgG and anti-TIF1γ-IgA showed the highest AUC among all possible combinations of four autoantibodies, up to 0.737, with 47.1% sensitivity at 92.0% specificity. Serum IgG autoantibodies against p53, HRAS and NSG1, and IgA autoantibody against TIF1γ show the diagnostic value for the patients with CC at early stage, of which anti-TIF1γ-IgA is demonstrated to be a preferable biomarker, and an optimal panel comprised of anti-p53, HRAS-IgG and anti-TIF1γ-IgA might contribute to the further improvement of early diagnosis for CC.
我们的初步研究通过 ELISA 显示，在早期结肠癌（CC）组中，血清 IgG 自身抗体针对 p53、HRAS 和 NSG1 以及针对 TIF1γ 的 IgA 自身抗体的水平和阳性率明显高于结肠良性病变（CBL）组/健康对照组（HC）（<0.01），这表明这四种自身抗体可能对早期 CC 患者的诊断有价值。在此初步研究的基础上，我们拟在大样本队列中全面阐明四种自身抗体对 CC 早期诊断的性能，并探讨早期诊断 CC 患者的最佳自身抗体组合。Western blot 用于定义血清抗 p53、HRAS、NSG1-IgG 和抗 TIF1γ-IgA 的 ELISA 结果。使用 157 例早期 CC 患者、144 例晚期 CC 患者、130 例 CBL 患者和 170 例 HC 的 601 份血清样本，通过 ELISA 评估抗 p53、HRAS、NSG1-IgG 和抗 TIF1γ-IgA 对 CC 的早期诊断性能，然后分析四种自身抗体不同组合的性能，以开发早期诊断 CC 的最佳组合。Western blot 中抗 p53、HRAS、NSG1-IgG 和抗 TIF1γ-IgA 的结果与 ELISA 一致。早期 CC 组的抗 p53、HRAS、NSG1-IgG 和抗 TIF1γ-IgA 水平和阳性率明显高于 CBL 组/HC 组（<0.01），但与晚期 CC 组无显著差异（>0.05），其中抗 TIF1γ-IgA 对早期 CC 患者的受试者工作特征曲线（ROC）下面积（AUC）最高，为 0.716，敏感性和特异性分别为 25.5%和 96.7%。此外，四种自身抗体的所有可能组合中，抗 p53、HRAS-IgG 和抗 TIF1γ-IgA 组成的面板的 AUC 最高，达 0.737，特异性为 92.0%时敏感性为 47.1%。血清 IgG 自身抗体针对 p53、HRAS 和 NSG1，以及针对 TIF1γ 的 IgA 自身抗体对早期 CC 患者具有诊断价值，其中抗 TIF1γ-IgA 被证明是一种较好的生物标志物，由抗 p53、HRAS-IgG 和抗 TIF1γ-IgA 组成的最佳组合可能有助于进一步提高 CC 的早期诊断。
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