Lung cancer (LC) accounts for the largest number of tumor-related deaths worldwide. As the overall 5-year survival rate of LC is associated with its stages at detection, development of a cost-effective and noninvasive cancer screening method is necessary. We conducted a systematic review to evaluate the diagnostic values of single and panel tumor-associated autoantibodies (TAAbs) in patients with LC. This review included 52 articles with 64 single TAAbs and 19 with 20 panels of TAAbs. Enzyme-linked immunosorbent assays (ELISA) were the most common detection method. The sensitivities of single TAAbs for all stages of LC ranged from 3.1% to 92.9% (mean: 45.2%, median: 37.1%), specificities from 60.6% to 100% (mean: 88.1%, median: 94.9%), and AUCs from 0.416 to 0.990 (mean: 0.764, median: 0.785). The single TAAb with the most significant diagnostic value was the autoantibody against human epididymis secretory protein (HE4) with the maximum sensitivity 91% for NSCLC. The sensitivities of the panel of TAAbs ranged from 30% to 94.8% (mean: 76.7%, median: 82%), specificities from 73% to 100% (mean: 86.8%, median: 89.0%), and AUCs from 0.630 to 0.982 (mean: 0.821, median: 0.820), and the most significant AUC value in a panel (M13 Phage 908, 3148, 1011, 3052, 1000) was 0.982. The single TAAb with the most significant diagnostic calue for early stage LC, was the autoantibody against Wilms tumor protein 1 (WT1) with the maximum sensitivity of 90.3% for NSCLC and its sensitivity and specificity in a panel (T7 Phage 72, 91, 96, 252, 286, 290) were both above 90.0%. Single or TAAbs panels may be useful biomarkers for detecting LC patients at all stages or an early-stage in high-risk populations or health people, but the TAAbs panels showed higher detection performance than single TAAbs. The diagnostic value of the panel of six TAAbs, which is higher than the panel of seven TAAbs, may be used as potential biomarkers for the early detection of LC and can probably be used in combination with low-dose CT in the clinic.
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