Analysis of GAGE, NY-ESO-1 and SP17 cancer/testis antigen expression in early stage non-small cell lung carcinoma

Abstract

BackgroundThe unique expression pattern and immunogenic properties of cancer/testis antigens make them ideal targets for immunotherapy of cancer. The MAGE-A3 cancer/testis antigen is frequently expressed in non-small cell lung cancer (NSCLC) and vaccination with MAGE-A3 in patients with MAGE-A3-positive NSCLC has shown promising results. However, little is known about the expression of other cancer/testis antigens in NSCLC. In the present study the expression of cancer/testis antigens GAGE, NY-ESO-1 and SP17 was investigated in patients with completely resected, early stage, primary NSCLC.MethodsTumor biopsies from normal lung tissue and from a large cohort (n = 169) of NSCLC patients were examined for GAGE, NY-ESO-1 and SP17 protein expression by immunohistochemical analysis. The expression of these antigens was further matched to clinical and pathological features using univariate cox regression analysis.ResultsGAGE and NY-ESO-1 cancer/testis antigens were not expressed in normal lung tissue, while SP17 was expressed in ciliated lung epithelia. The frequency of GAGE, NY-ESO-1 and SP17 expression in NSCLC tumors were 26.0% (44/169), 11.8% (20/169) and 4.7% (8/169), respectively, and 33.1% (56/169) of the tumors expressed at least one of these antigens. In general, the expression of GAGE, NY-ESO-1 and SP17 was not significantly associated with a specific histotype (adenocarcinoma vs. squamous cell carcinoma), but high-level GAGE expression (>50%) was more frequent in squamous cell carcinoma (p = 0.02). Furthermore, the frequency of GAGE expression was demonstrated to be significantly higher in stage II-IIIa than stage I NSCLC (17.0% vs. 35.8%; p = 0.02). Analysis of the relation between tumor expression of GAGE and NY-ESO-1 and survival endpoints revealed no significant associations.ConclusionOur study demonstrates that GAGE, NY-ESO-1 and SP17 cancer/testis antigens are candidate targets for immunotherapy of NSCLC and further suggest that multi-antigen vaccines may be beneficial.

Exosomal proteins as prognostic biomarkers in non‐small cell lung cancer

“…Studies have evaluated the gene expression of NY-ESO-1 in NSCLC and found that it is present in 15e30% of lung cancer samples. However, our results were conflicting when NY-ESO-1 was correlated with OS (Gjerstorff et al, 2013;Grah et al, 2014;Konishi et al, 2004). In the present study, we found exosomal NY-ESO-1 in 50% of the patients.…”

SSX2‐4 expression in early‐stage non‐small cell lung cancer

“…However, in a previous study of NSCLC tumors from the same patient material, we found relatively high expression frequencies of other cancer/testis antigens, i.e. GAGE (26%), NY‐ESO‐1 (11%), and SP17 (5%) using only two cores per patient .…”

New York Esophageal Squamous Cell Carcinoma-1 and Cancer Immunotherapy

“…Higher frequency of gene expression detected in a specific tumor type by RT-PCR than IHC is due to higher sensitivity of RT-PCR. An unexpected discrepancy between the mRNA and protein expressions has been observed in medulloblastoma, which has been attributed to possible posttranscriptional control of CTAs in this kind of cancer or sample bias due to the heterogeneous expression of CTAs at both the mRNA and protein level [43]. More recent studies have used quantitative real-time PCR (qRT-PCR) which has the advantage of providing quantification for levels of gene expression.…”

“…Analysis of protein expression by IHC provides invaluable data about the intratumoral distribution of NY-ESO-1, revealing its intratumoral heterogeneity [44]. However, it is anticipated that antigens with relative homo geneity of expression in a certain tumor are more suitable targets for immunotherapy compared with those with scattered expression [43]. The variations observed between different protein studies in the frequency of NY-ESO-1 expression in a specific tumor type may be at least partly due to different detection methods and different antibodies used for NY-ESO-1 detection.…”

“…Early stage, primary 11.8%(20/169)/IHC/E978 [43] 1/42 (2%)/RT-PCR [129] 7/33 (21%)/RT-PCR [137] 139/523 (27%)/RT-PCR [138] 20/63 (32%)/RT-PCR [139] 25/239 (10%)/RT-PCR [140] Primary operable tumor…”