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Title: The role of Cancer-Testis antigens as predictive and prognostic markers in non-small cell lung cancer.
Austin Authors: John, Thomas ;Starmans, Maud H W;Chen, Yao-Tseng;Russell, Prudence A;Barnett, Stephen A ;White, Shane C;Mitchell, Paul L R ;Walkiewicz, Marzena;Azad, Arun A;Lambin, Philippe;Tsao, Ming-Sound;Deb, Siddhartha;Altorki, Nasser;Wright, Gavin;Knight, Simon R ;Boutros, Paul C;Cebon, Jonathan S 
Affiliation: Ludwig Institute for Cancer Research, Austin Health, Melbourne, Australia
Issue Date: 23-Jul-2013
Publication information: PLoS One 2013; 8(7): e67876
Abstract: Cancer-Testis Antigens (CTAs) are immunogenic proteins that are poor prognostic markers in non-small cell lung cancer (NSCLC). We investigated expression of CTAs in NSCLC and their association with response to chemotherapy, genetic mutations and survival.We studied 199 patients with pathological N2 NSCLC treated with neoadjuvant chemotherapy (NAC; n = 94), post-operative observation (n = 49), adjuvant chemotherapy (n = 47) or unknown (n = 9). Immunohistochemistry for NY-ESO-1, MAGE-A and MAGE-C1 was performed. Clinicopathological features, response to neoadjuvant treatment and overall survival were correlated. DNA mutations were characterized using the Sequenom Oncocarta panel v1.0. Affymetrix data from the JBR.10 adjuvant chemotherapy study were obtained from a public repository, normalised and mapped for CTAs.NY-ESO-1 was expressed in 50/199 (25%) samples. Expression of NY-ESO-1 in the NAC cohort was associated with significantly increased response rates (P = 0.03), but not overall survival. In the post-operative cohort, multivariate analyses identified NY-ESO-1 as an independent poor prognostic marker for those not treated with chemotherapy (HR 2.61, 95% CI 1.28-5.33; P = 0.008), whereas treatment with chemotherapy and expression of NY-ESO-1 was an independent predictor of improved survival (HR 0.267, 95% CI 0.07-0.980; P = 0.046). Similar findings for MAGE-A were seen, but did not meet statistical significance. Independent gene expression data from the JBR.10 dataset support these findings but were underpowered to demonstrate significant differences. There was no association between oncogenic mutations and CTA expression.NY-ESO-1 was predictive of increased response to neoadjuvant chemotherapy and benefit from adjuvant chemotherapy. Further studies investigating the relationship between these findings and immune mechanisms are warranted.
Gov't Doc #: 23935846
DOI: 10.1371/journal.pone.0067876
Journal: PLoS One
Type: Journal Article
Subjects: Adult
Aged, 80 and over
Antigens, Neoplasm.genetics.metabolism
Carcinoma, Non-Small-Cell Lung.drug therapy.genetics.metabolism.pathology
Cohort Studies
Gene Expression Regulation, Neoplastic
Lung Neoplasms.drug therapy.genetics.metabolism.pathology
Membrane Proteins.genetics.metabolism
Middle Aged
Multivariate Analysis
Neoadjuvant Therapy
Survival Analysis
Treatment Outcome
Tumor Markers, Biological.metabolism
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