Case-Control Study: Smoking History Affects the Production of Tumor Antigen–Specific Antibodies NY-ESO-1 in Patients with Lung Cancer in Comparison with Cancer Disease–Free Group

Myšíková, D.; Adkins, Irena; Hradilova, Nada; Palata, Ondřej; J, Simonek; Pozniak, J.; Kolařík, J; Fialová, Alena; Špíšek, Radek; Lischke, Robert

doi:10.1016/j.jtho.2016.09.136

Cited by 10 publications

(6 citation statements)

References 37 publications

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“…Given promoter hypermethylation leads to epigenetic silencing, it is therefore predicted that a larger proportion of SCC would be NY-ESO-1 positive when compared to ADC. In fact, this prediction held true based on the findings made in our prior study [ 15 ] and is in close agreement to what was previously reported in several independent lung cancer patient cohorts [ 8 , 9 , 18 – 20 ]. Interestingly, SCC is not only more likely to express NY-ESO-1 but also appears to respond better to immunotherapy, regardless of PD-L1 expression [ 21 , 22 ].…”

Section: Discussionsupporting

confidence: 92%

Promoter hypomethylation of NY-ESO-1, association with clinicopathological features and PD-L1 expression in non-small cell lung cancer

et al. 2017

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Cancer-Testis antigens (CTA) are immunogenic molecules with normal tissue expression restricted to testes but with aberrant expression in up to 30% of non-small cell lung cancers (NSCLCs). Regulation of CTA expression is mediated in part through promoter DNA methylation. Recently, immunotherapy has altered treatment paradigms in NSCLC. Given its immunogenicity and ability to be re-expressed through demethylation, NY-ESO-1 promoter methylation, protein expression and its association with programmed death receptor ligand-1 (PD-L1) expression and clinicopathological features were investigated. Lung cancer cell line demethylation resulting from 5-Aza-2′-deoxycytidine treatment was associated with both NY-ESO-1 and PD-L1 re-expression in vitro but not increased chemosensitivity. NY-ESO-1 hypomethylation was observed in 15/94 (16%) of patient samples and associated with positive protein expression (P < 0.0001). In contrast, PD-L1 expression was observed in 50/91 (55%) but strong expression in only 12/91 (13%) cases. There was no association between NY-ESO-1 and PD-L1 expression, despite resultant re-expression of both by 5-Aza-2′-deoxycytidine. Importantly, NY-ESO-1 hypomethylation was found to be an independent marker of poor prognosis in patients not treated with chemotherapy (HR 3.59, P = 0.003) in multivariate analysis. In patients treated with chemotherapy there were no differences in survival associated with NY-ESO-1 hypomethylation. Collectively, these results provided supporting evidence for the potential use of NY-ESO-1 hypomethylation as a prognostic biomarker in stage 3 NSCLCs. In addition, these data highlight the potential to incorporate demethylating agents to enhance immune activation, in tumours currently devoid of immune infiltrates and expression of immune checkpoint genes.

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Section: Discussionsupporting

confidence: 92%

Promoter hypomethylation of NY-ESO-1, association with clinicopathological features and PD-L1 expression in non-small cell lung cancer

et al. 2017

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“…In brief, autoantibodies to p53 tumor suppressor gene, which is often mutated in a variety of malignancies (including in lung, colorectal and breast cancer), can be detected before the diagnosis of cancer in smokers with chronic obstructive pulmonary disease [ 97 ]. Besides expressed in prostate, breast, colorectal cancer and melanoma patients, the presence of antibodies to NY-ESO-1 were significantly elevated in NSCLC patients with an active smoking history and was more expressed in early NSCLC stages than in late stage [ 66 , 98 ]. CAGE has been reported in a variety of cancers, but not in normal tissues [ 99 ].…”

Section: Discussionmentioning

confidence: 99%

“…It is possible that adding melanoma-associated antigen A4 (MAGE-A4) and HuD to the panel, which are known to have particular associations with lung cancer, may improve the sensitivity and optimize the test accuracy. MAGE A4 has been demonstrated to be expressed in melanomas and NSCLC patients (male gender, with a smoking history), especially in squamous cell carcinoma patients [ 98 , 100 , 101 ]. Approximately half of squamous cell carcinoma (SCC) expressed MAGE-A4 [ 102 ], and MAGE A4 has been proposed as a potential therapeutic target for immunotherapy [ 103 ].…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2017

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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.

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“…Twelve articles reported on the autoantibody against p53 9,10,51,54–62 , and found sensitivities ranging from 12.6% to 40.3% and specificities ranging from 94.9% to 100%. Three articles reported on the autoantibody against New York esophageal squamous cell carcinoma-1 (NY-ESO-1), and reported sensitivities from 26.3% to 47%, and specificities from 80.0% to 96.5% 63–65 . Two articles reported on the autoantibody against cyclin B1, with the sensitivities of 13.3% and 20%, and specificities of 96.6% and 97.6% 9,10 .…”

Section: Diagnostic Value Of Single Taab At All Stages Of Lcmentioning

confidence: 99%

Autoantibodies as diagnostic biomarkers for lung cancer: A systematic review

Yang

Ren

et al. 2019

Cell Death Discov.

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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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Case-Control Study: Smoking History Affects the Production of Tumor Antigen–Specific Antibodies NY-ESO-1 in Patients with Lung Cancer in Comparison with Cancer Disease–Free Group

Cited by 10 publications

References 37 publications

Promoter hypomethylation of NY-ESO-1, association with clinicopathological features and PD-L1 expression in non-small cell lung cancer

Promoter hypomethylation of NY-ESO-1, association with clinicopathological features and PD-L1 expression in non-small cell lung cancer

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

Autoantibodies as diagnostic biomarkers for lung cancer: A systematic review

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