Dataset Information

The role of Cancer-Testis antigens as predictive and prognostic markers in non-small cell lung cancer.

ABSTRACT:

Background

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.

Methods

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.

Results

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.

Conclusions

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.

SUBMITTER: John T

PROVIDER: S-EPMC3720740 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

The role of Cancer-Testis antigens as predictive and prognostic markers in non-small cell lung cancer.

John Thomas T Starmans Maud H W MH Chen Yao-Tseng YT Russell Prudence A PA Barnett Stephen A SA White Shane C SC Mitchell Paul L PL Walkiewicz Marzena M Azad Arun A Lambin Philippe P Tsao Ming-Sound MS Deb Siddhartha S Altorki Nasser N Wright Gavin G Knight Simon S Boutros Paul C PC Cebon Jonathan S JS

PloS one 20130723 7

<h4>Background</h4>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.<h4>Methods</h4>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). Immunohistochemist ...[more]

PMID: 23935846

Similar Datasets

Project description:BackgroundThe 5-year survival rate of non-small cell lung cancer (NSCLC) patients has not significantly improved despite advancements in the currently applied treatments. Thus, efforts are put forth in developing novel immunotherapeutic agents targeting cancer-testis antigens (CTA) in NSCLC. This work utilized reverse vaccinology approach in designing a novel multi-epitope vaccine targeting melanoma-associated antigen 3 (MAGEA3), MAGEA4, New York esophageal squamous cell carcinoma-1 (NY-ESO-1), and Kita-Kyushu lung cancer antigen 1 (KK-LC1), being the most frequently expressed CTAs in NSCLC.MethodsEpitopes were mapped from the sequences of CTAs. The population coverage (PC) of identified CD4+ and CD8+ epitopes were estimated. Candidate linear B cell (BL), CD4+, and CD8+ epitopes were adjoined in a multi-epitope construct (Mvax) with flagellin domain as an adjuvant. Antigenicity, and cross-reactivity of Mvax were examined. The tertiary structure of Mvax was modelled, and validated. All epitopes included in the vaccine were docked with their human leukocyte antigen (HLA) binders. The immunogenicity of epitopes in Mvax was validated through molecular dynamics analysis.ResultsMvax contains 22 epitopes from MAGEA3, MAGEA4, NY-ESO-1, and KK-LC1. It is classified as antigenic, non-allergen, non-toxic, and possesses physicochemical stability. Epitopes have no significant hits with other human proteins, except for 2 other CTAs frequently expressed in NSCLC. The stretch of BL epitopes in Mvax confers flexibility, and accessibility emphasizing its antigenicity. The tertiary structure analysis showed that Mvax model has good structural quality. All epitopes included in the vaccine are highly immunogenic as indicated by favorable binding affinity, low binding energy, and acceptable root-mean-square deviation (RMSD). CD4+ and CD8+ epitopes have global PC of 81.81%, and 84.15%, respectively.ConclusionOverall, in silico evaluations show that Mvax is a potential immunotherapeutic agent against NSCLC.

Dataset Information

The role of Cancer-Testis antigens as predictive and prognostic markers in non-small cell lung cancer.

Background

Methods

Results

Conclusions

Publications

The role of Cancer-Testis antigens as predictive and prognostic markers in non-small cell lung cancer.

Similar Datasets

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