Abstract
ObjectiveWe performed a comprehensive review and meta-analysis to evaluate the diagnostic values of serum single and multiplex tumor-associated autoantibodies (TAAbs) in patients with lung cancer (LC).MethodsWe searched the MEDLINE and EMBASE databases for relevant studies investigating serum TAAbs for the diagnosis of LC. The primary outcomes included sensitivity, specificity and accuracy of the test.ResultsThe systematic review and meta-analysis included 31 articles with single autoantibody and 39 with multiplex autoantibodies. Enzyme-linked immunosorbent assay (ELISA) was the most common detection method. For the diagnosis of patients with all stages and early-stage LC, different single or combinations of TAAbs demonstrated different diagnostic values. Although individual TAAbs showed low diagnostic sensitivity, the combination of multiplex autoantibodies offered relatively high sensitivity. For the meta-analysis of a same panel of autoantibodies in patients at all stages of LC, the pooled results of the panel of 6 TAAbs (p53, NY-ESO-1, CAGE, GBU4-5, Annexin 1 and SOX2) were: sensitivity 38% (95% CI 0.35–0.40), specificity 89% (95% CI 0.86–0.91), diagnostic accuracy 65.9% (range 62.5–81.8%), AUC 0.52 (0.48–0.57), while the summary estimates of 7 TAAbs (p53, CAGE, NY-ESO-1, GBU4-5, SOX2, MAGE A4 and Hu-D) were: sensitivity 47% (95% CI 0.34–0.60), specificity 90% (95% CI 0.89–0.92), diagnostic accuracy 78.4% (range 67.5–88.8%), AUC 0.90 (0.87–0.93). For the meta-analysis of the same panel of autoantibodies in patients at early-stage of LC, the sensitivities of both panels of 7 TAAbs and 6 TAAbs were 40% and 29.7%, while their specificities were 91% and 87%, respectively.ConclusionsSerum single or combinations of multiplex autoantibodies can be used as a tool for the diagnosis of LC patients at all stages or early-stage, but the combination of multiplex autoantibodies shows a higher detection capacity; the diagnostic value of the panel of 7 TAAbs is higher than the panel of 6 TAAbs, which may be used as potential biomarkers for the early detection of LC.
Highlights
lung cancer (LC) is the most common malignant tumor and the leading cause of cancer death for both sexes worldwide [1,2]
For the meta-analysis of a same panel of autoantibodies in patients at all stages of LC, the pooled results of the panel of 6 tumor-associated autoantibodies (TAAbs) (p53, NY-ESO-1, CAGE, GBU4-5, Annexin 1 and SOX2) were: sensitivity 38%, specificity 89%, diagnostic accuracy 65.9%, area under the curve (AUC) 0.52 (0.48–0.57), while the summary estimates of 7 TAAbs (p53, CAGE, NYESO-1, GBU4-5, SOX2, MAGE A4 and Hu-D) were: sensitivity 47%, specificity 90%, diagnostic accuracy 78.4%, AUC 0.90 (0.87–0.93)
Serum single or combinations of multiplex autoantibodies can be used as a tool for the diagnosis of LC patients at all stages or early-stage, but the combination of multiplex autoantibodies shows a higher detection capacity; the diagnostic value of the panel of 7 TAAbs is higher than the panel of 6 TAAbs, which may be used as potential biomarkers for the early detection of LC
Summary
LC is the most common malignant tumor and the leading cause of cancer death for both sexes worldwide [1,2]. The average 5-year survival of LC patients is only 17%; in most patients, LC is usually advanced at the time of diagnosis, with 5-year survival rates as low as only 4% [3]. Few early detection tests or acceptable screening methods for this disease are available. Low-dose spiral computed tomography (LDCT) has been shown to be highly sensitive for the early detection of small lung nodules and has led to a 20% reduction in LC mortality [7]. LDCT presents several limitations, including a high false-positive rate (as high as 50% in prevalence), repeated radiation exposure and substantial costs, which limit its widespread application as a screening procedure [8,9,10]. It is necessary to develop more effective, non-invasive methods for the screening and early diagnosis of LC
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