A five-gene and corresponding protein signature for stage-I lung adenocarcinoma prognosis

Humam Kadara, Carmen Behrens, Ping Yuan, Luisa Solis, Diane Liu, Xuemin Gu, John D. Minna, J. Jack Lee, Edward Kim, Waun Ki Hong, Ignacio I. Wistuba, Reuben Lotan

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Abstract

Purpose: Identification of effective markers for outcome is expected to improve the clinical management of non-small cell lung cancer (NSCLC). Here, we assessed in NSCLC the prognostic efficacy of genes, which we had previously found to be differentially expressed in an in vitro model of human lung carcinogenesis. Experimental Design: Prediction algorithms and risk-score models were applied to the expression of the genes in publicly available NSCLC expression data sets. The prognostic capacity of the immunohistochemical expression of proteins encoded by these genes was also tested using formalin-fixed paraffinembedded (FFPE) tissue specimens from 156 lung adenocarcinomas and 79 squamous cell carcinomas (SCCs). Results: The survival of all-stages (P < 0.001, HR = 2.0) or stage-I (P < 0.001, HR = 2.84) adenocarcinoma patients that expressed the five-gene in vitro lung carcinogenesis model (FILM) signature was significantly poorer than that of patients who did not. No survival differences were observed between SCCs predicted to express or lack FILM signature. Moreover, all stages (P < 0.001, HR = 1.95) or stage-I (P = 0.001, HR = 2.6) adenocarcinoma patients predicted to be at high risk by FILM transcript exhibited significantly worse survival than patients at low risk. Furthermore, the corresponding protein signature was associated with poor survival (all stages, P < 0.001, HR = 3.6; stage-I, P < 0.001, HR = 3.5; stage-IB, P < 0.001, HR = 4.6) and mortality risk (all stages, P = 0.001, HR = 4.0; stage-I, P = 0.01, HR = 3.4; stage-IB, P < 0.001, HR = 7.2) in lung adenocarcinoma patients. Conclusions: Our findings highlight a gene and corresponding protein signature with effective capacity for identification of stage-I lung adenocarcinoma patients with poor prognosis that are likely to benefit from adjuvant therapy.

Original languageEnglish (US)
Pages (from-to)1490-1501
Number of pages12
JournalClinical Cancer Research
Volume17
Issue number6
DOIs
StatePublished - Mar 15 2011

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Non-Small Cell Lung Carcinoma
Proteins
Survival
Squamous Cell Carcinoma
Carcinogenesis
Adenocarcinoma
Lung
Formaldehyde
Genes
Adenocarcinoma of lung
Research Design
Gene Expression
Mortality
In Vitro Techniques
Therapeutics
Datasets

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Kadara, H., Behrens, C., Yuan, P., Solis, L., Liu, D., Gu, X., ... Lotan, R. (2011). A five-gene and corresponding protein signature for stage-I lung adenocarcinoma prognosis. Clinical Cancer Research, 17(6), 1490-1501. https://doi.org/10.1158/1078-0432.CCR-10-2703

A five-gene and corresponding protein signature for stage-I lung adenocarcinoma prognosis. / Kadara, Humam; Behrens, Carmen; Yuan, Ping; Solis, Luisa; Liu, Diane; Gu, Xuemin; Minna, John D.; Lee, J. Jack; Kim, Edward; Hong, Waun Ki; Wistuba, Ignacio I.; Lotan, Reuben.

In: Clinical Cancer Research, Vol. 17, No. 6, 15.03.2011, p. 1490-1501.

Research output: Contribution to journalArticle

Kadara, H, Behrens, C, Yuan, P, Solis, L, Liu, D, Gu, X, Minna, JD, Lee, JJ, Kim, E, Hong, WK, Wistuba, II & Lotan, R 2011, 'A five-gene and corresponding protein signature for stage-I lung adenocarcinoma prognosis', Clinical Cancer Research, vol. 17, no. 6, pp. 1490-1501. https://doi.org/10.1158/1078-0432.CCR-10-2703
Kadara, Humam ; Behrens, Carmen ; Yuan, Ping ; Solis, Luisa ; Liu, Diane ; Gu, Xuemin ; Minna, John D. ; Lee, J. Jack ; Kim, Edward ; Hong, Waun Ki ; Wistuba, Ignacio I. ; Lotan, Reuben. / A five-gene and corresponding protein signature for stage-I lung adenocarcinoma prognosis. In: Clinical Cancer Research. 2011 ; Vol. 17, No. 6. pp. 1490-1501.
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abstract = "Purpose: Identification of effective markers for outcome is expected to improve the clinical management of non-small cell lung cancer (NSCLC). Here, we assessed in NSCLC the prognostic efficacy of genes, which we had previously found to be differentially expressed in an in vitro model of human lung carcinogenesis. Experimental Design: Prediction algorithms and risk-score models were applied to the expression of the genes in publicly available NSCLC expression data sets. The prognostic capacity of the immunohistochemical expression of proteins encoded by these genes was also tested using formalin-fixed paraffinembedded (FFPE) tissue specimens from 156 lung adenocarcinomas and 79 squamous cell carcinomas (SCCs). Results: The survival of all-stages (P < 0.001, HR = 2.0) or stage-I (P < 0.001, HR = 2.84) adenocarcinoma patients that expressed the five-gene in vitro lung carcinogenesis model (FILM) signature was significantly poorer than that of patients who did not. No survival differences were observed between SCCs predicted to express or lack FILM signature. Moreover, all stages (P < 0.001, HR = 1.95) or stage-I (P = 0.001, HR = 2.6) adenocarcinoma patients predicted to be at high risk by FILM transcript exhibited significantly worse survival than patients at low risk. Furthermore, the corresponding protein signature was associated with poor survival (all stages, P < 0.001, HR = 3.6; stage-I, P < 0.001, HR = 3.5; stage-IB, P < 0.001, HR = 4.6) and mortality risk (all stages, P = 0.001, HR = 4.0; stage-I, P = 0.01, HR = 3.4; stage-IB, P < 0.001, HR = 7.2) in lung adenocarcinoma patients. Conclusions: Our findings highlight a gene and corresponding protein signature with effective capacity for identification of stage-I lung adenocarcinoma patients with poor prognosis that are likely to benefit from adjuvant therapy.",
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AU - Kadara, Humam

AU - Behrens, Carmen

AU - Yuan, Ping

AU - Solis, Luisa

AU - Liu, Diane

AU - Gu, Xuemin

AU - Minna, John D.

AU - Lee, J. Jack

AU - Kim, Edward

AU - Hong, Waun Ki

AU - Wistuba, Ignacio I.

AU - Lotan, Reuben

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N2 - Purpose: Identification of effective markers for outcome is expected to improve the clinical management of non-small cell lung cancer (NSCLC). Here, we assessed in NSCLC the prognostic efficacy of genes, which we had previously found to be differentially expressed in an in vitro model of human lung carcinogenesis. Experimental Design: Prediction algorithms and risk-score models were applied to the expression of the genes in publicly available NSCLC expression data sets. The prognostic capacity of the immunohistochemical expression of proteins encoded by these genes was also tested using formalin-fixed paraffinembedded (FFPE) tissue specimens from 156 lung adenocarcinomas and 79 squamous cell carcinomas (SCCs). Results: The survival of all-stages (P < 0.001, HR = 2.0) or stage-I (P < 0.001, HR = 2.84) adenocarcinoma patients that expressed the five-gene in vitro lung carcinogenesis model (FILM) signature was significantly poorer than that of patients who did not. No survival differences were observed between SCCs predicted to express or lack FILM signature. Moreover, all stages (P < 0.001, HR = 1.95) or stage-I (P = 0.001, HR = 2.6) adenocarcinoma patients predicted to be at high risk by FILM transcript exhibited significantly worse survival than patients at low risk. Furthermore, the corresponding protein signature was associated with poor survival (all stages, P < 0.001, HR = 3.6; stage-I, P < 0.001, HR = 3.5; stage-IB, P < 0.001, HR = 4.6) and mortality risk (all stages, P = 0.001, HR = 4.0; stage-I, P = 0.01, HR = 3.4; stage-IB, P < 0.001, HR = 7.2) in lung adenocarcinoma patients. Conclusions: Our findings highlight a gene and corresponding protein signature with effective capacity for identification of stage-I lung adenocarcinoma patients with poor prognosis that are likely to benefit from adjuvant therapy.

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