The Role of Cancer-Testis Antigens as Predictive and Prognostic Markers in Non-Small Cell Lung Cancer

Thomas John, Maud H W Starmans, Yao-Tseng Chen, Prudence A Russell, Stephen A Barnett, Shane C White, Paul Mitchell, Marzena Walkiewicz, Arun Azad, Phillipe Lambin, Ming-Sound Tsao, Siddhartha Deb, Nasser K Altorki, Gavin Michael Wright, Simon Knight, Paul C Boutros, Jonathan Cebon

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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.
Original languageEnglish
Pages (from-to)1 - 8
Number of pages8
JournalPLoS ONE
Volume8
Issue number7
DOIs
Publication statusPublished - 2013
Externally publishedYes

Cite this

John, T., Starmans, M. H. W., Chen, Y-T., Russell, P. A., Barnett, S. A., White, S. C., ... Cebon, J. (2013). The Role of Cancer-Testis Antigens as Predictive and Prognostic Markers in Non-Small Cell Lung Cancer. PLoS ONE, 8(7), 1 - 8. https://doi.org/10.1371/journal.pone.0067876
John, Thomas ; Starmans, Maud H W ; Chen, Yao-Tseng ; Russell, Prudence A ; Barnett, Stephen A ; White, Shane C ; Mitchell, Paul ; Walkiewicz, Marzena ; Azad, Arun ; Lambin, Phillipe ; Tsao, Ming-Sound ; Deb, Siddhartha ; Altorki, Nasser K ; Wright, Gavin Michael ; Knight, Simon ; Boutros, Paul C ; Cebon, Jonathan. / The Role of Cancer-Testis Antigens as Predictive and Prognostic Markers in Non-Small Cell Lung Cancer. In: PLoS ONE. 2013 ; Vol. 8, No. 7. pp. 1 - 8.
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title = "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.",
author = "Thomas John and Starmans, {Maud H W} and Yao-Tseng Chen and Russell, {Prudence A} and Barnett, {Stephen A} and White, {Shane C} and Paul Mitchell and Marzena Walkiewicz and Arun Azad and Phillipe Lambin and Ming-Sound Tsao and Siddhartha Deb and Altorki, {Nasser K} and Wright, {Gavin Michael} and Simon Knight and Boutros, {Paul C} and Jonathan Cebon",
year = "2013",
doi = "10.1371/journal.pone.0067876",
language = "English",
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John, T, Starmans, MHW, Chen, Y-T, Russell, PA, Barnett, SA, White, SC, Mitchell, P, Walkiewicz, M, Azad, A, Lambin, P, Tsao, M-S, Deb, S, Altorki, NK, Wright, GM, Knight, S, Boutros, PC & Cebon, J 2013, 'The Role of Cancer-Testis Antigens as Predictive and Prognostic Markers in Non-Small Cell Lung Cancer', PLoS ONE, vol. 8, no. 7, pp. 1 - 8. https://doi.org/10.1371/journal.pone.0067876

The Role of Cancer-Testis Antigens as Predictive and Prognostic Markers in Non-Small Cell Lung Cancer. / John, Thomas; Starmans, Maud H W; Chen, Yao-Tseng; Russell, Prudence A; Barnett, Stephen A; White, Shane C; Mitchell, Paul; Walkiewicz, Marzena; Azad, Arun; Lambin, Phillipe; Tsao, Ming-Sound; Deb, Siddhartha; Altorki, Nasser K; Wright, Gavin Michael; Knight, Simon; Boutros, Paul C; Cebon, Jonathan.

In: PLoS ONE, Vol. 8, No. 7, 2013, p. 1 - 8.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - The Role of Cancer-Testis Antigens as Predictive and Prognostic Markers in Non-Small Cell Lung Cancer

AU - John, Thomas

AU - Starmans, Maud H W

AU - Chen, Yao-Tseng

AU - Russell, Prudence A

AU - Barnett, Stephen A

AU - White, Shane C

AU - Mitchell, Paul

AU - Walkiewicz, Marzena

AU - Azad, Arun

AU - Lambin, Phillipe

AU - Tsao, Ming-Sound

AU - Deb, Siddhartha

AU - Altorki, Nasser K

AU - Wright, Gavin Michael

AU - Knight, Simon

AU - Boutros, Paul C

AU - Cebon, Jonathan

PY - 2013

Y1 - 2013

N2 - 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.

AB - 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.

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DO - 10.1371/journal.pone.0067876

M3 - Article

VL - 8

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EP - 8

JO - PLoS ONE

JF - PLoS ONE

SN - 1932-6203

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