Serum tumor-associated autoantibodies as diagnostic biomarkers for lung cancer: A systematic review and meta-analysis

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.

Diagnostic Value of Autoantibodies in Lung Cancer: a Systematic Review and Meta-Analysis

“…One recent review [109] indicated different single or combinations of multiple TAAbs have different diagnostic abilities for detecting patients at all stages of lung cancer, while the review did not report sensitivity, specificity and AUC for each TAAb. In our systematic review, each TAAb was analyzed using bivariate mixedeffect models, and larger numbers of references were included.…”

“…Other TAAbs were excluded from the review because relevant data were available from fewer than 3 articles . Five of the included studies examined only small-cell lung cancer (SCLC) [45,50,52,58,67], and eight included only non-small cell lung cancer (NSCLC) [28,47,54,55,57,59,64,109]. A total of 50 articles were based on serum specimens, while the remaining 3 were based on plasma samples.…”

Tumor‐associated autoantibodies as early detection markers for ovarian cancer? A prospective evaluation

“…The higher sensitivity and specificity of P53 AAb for high-grade serous tumors is likely related to the uniform occurrence of P53 mutations, with dysregulated P53 protein levels, in high-grade serous tumors. Like the P53 AAbs, elevated titers of AAbs to the cancer-testis antigens CTAG1A (NY-ESO-1) and CTAG2 (ESO2) have been observed in relation to a wide variety of cancer types 6–814, 15 , including ovarian cancer 20913 , and are likely related to the generally less differentiated nature of cancer cells, with aberrant expression of proteins that normally are expressed only in embryonic tissue types. AAbs to NUDT11 were first discovered as ovarian autoantigens through our own immuno-proteomic screening of ovarian cancer patients and controls 18 .…”

“…of AAbs to the cancer-testis antigens CTAG1A (NY-ESO-1) and CTAG2 (ESO2) have been observed in relation to a wide variety of cancer types, [6][7][8]14,15 including ovarian cancer, 9,13,20 and are likely related to the generally less differentiated nature of cancer cells, with aberrant expression of proteins that normally are expressed only in embryonic tissue types. AAbs to NUDT11 were first discovered as ovarian autoantigens through our own immuno-proteomic screening of ovarian cancer patients and controls.…”

“…Among these, antibodies against p53, the cancer/testis antigen CTAG-2 (also known as ESO2), and NUDT11 stood out as AAb markers with highest diagnostic sensitivity (up to 27.3 and 36.4%, respectively for serous tumors) at ≥97% specificity. A further AAb frequently reported to be associated with ovarian cancer 139 and other tumors types 14, 15 , is CTAG1A (also known as NY-ESO-01). However, with the exception of two recent studies on AAbs against MUC1 (Ca15.3) 16 and p53 17 , the early detection potential of tumor associated AAbs for ovarian cancer has been insufficiently evaluated in prospective cohort studies based on pre-diagnostic serum samples, and it is still unclear whether elevated AAb levels can be used to reliably detect ovarian cancer ahead of usual diagnosis.…”