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

Abstract

Background/Aims: Recently, many studies have demonstrated that various tumor-associated autoantibodies have been detected in early stages of lung cancer. Therefore, we conducted a meta-analysis to comprehensively evaluate available evidence on the diagnostic value of autoantibodies against tumor-associated antigens in lung cancer. Methods: We systematically searched PubMed, Scopus, Web of Science and other databases through 23 March 2018. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. We used the bivariate mixed-effect models to calculate pooled values of sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, diagnostic odds ratios and associated 95% confidence intervals. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. Deek’s funnel plot was used to detect publication bias. Results: Review of 468 candidate articles identified fifty-three articles with a total of 11,515 patients for qualitative review and meta-analysis. Pooled sensitivity, specificity and area under the SROC curve were as follows for tumor-associated autoantibodies against the following proteins: p53, 0.19, 0.98, 0.82; NY-ESO-1, 0.17, 0.98, 0.90; Survivin, 0.19, 0.99, 0.96; c-myc, 0.14, 0.98, 0.45; Cyclin B1, 0.18, 0.98, 0.91; GBU4-5, 0.07, 0.98, 0.91; CAGE, 0.14, 0.98, 0.90; p16, 0.08, 0.97, 0.91; SOX2, 0.14, 0.99, 0.93; and HuD, 0.17, 0.99, 0.82. Conclusion: Each tumor-associated autoantibody on its own showed excellent diagnostic specificity for lung cancer but inadequate sensitivity. Our results suggest that combinations or panels of tumor-associated autoantibodies may provide better sensitivity for diagnosing lung cancer, and the diagnostic accuracy of tumor-associated autoantibodies should be validated in more studies.

Methylated PTGER4 is better than CA125, CEA, Cyfra211 and NSE as a therapeutic response assessment marker in stage IV lung cancer

“…Protein markers were first discovered to have a strong correlation with the occurrence of tumors, but later studies revealed that the majority of protein markers are unable to detect early-stage tumors (17)(18)(19). Protein markers are particularly elevated during tumor recurrence and are generally associated with tumors in more advanced stages (17).…”

“…Hence, protein tumor markers are predominantly used for recurrence monitoring. An increased level of certain blood protein markers is associated with tumor progression, while a decreased level is an indication of tumor remission (17)(18)(19). However, significant changes in blood protein level may not be observed in a group of patients due to variation between individuals.…”

“…However, protein markers also have certain advantages. For instance, their specificity for cancer is generally better with a low false-positive rate in healthy subjects, suggesting that the potential of measuring levels of protein markers in the blood requires further investigation (17)(18)(19). By contrast, the positive detection rate of methylation markers is generally higher in older patients, with an increased false positive rate in healthy elderly subjects (26,27).…”

“…Therefore, response monitoring with blood markers may be an ideal method, but it requires high sensitivity markers that exhibit a good correlation with changes in tumor burden. Previous studies have revealed that both methylation and protein markers can be used for response monitoring, but not all changes in blood marker levels were correlated with tumor burden, and there is a large variation between individuals (17)(18)(19). These issues warrant further investigation to characterize the performance of individual markers.…”

“…Conversely, protein markers are not as potent as methylation markers, due to their unsatisfactory PDR even in advanced cancer, thus limiting their use in monitoring techniques (8)(9)(10)17). However, the specificity of protein markers is generally satisfactory (18,19), therefore, they are often better indicators of recurrence instead.…”