Serpin B3 is associated with poor survival after chemotherapy and is a potential novel predictive biomarker in advanced non-small-cell lung cancer

Gordon Urquhart, Keith M. Kerr, Marianne Nicolson, Peh Sun Loo, Ravi Sharma, Raj Shrimali, Russell D. Petty (Lead / Corresponding author)

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    INTRODUCTION: In a previous biomarker discovery project using gene-expression profiling we identified Serpin B3 (SB3) as a predictor of resistance to platinum doublet chemotherapy (PtC) in non-small-cell lung cancer (NSCLC). This independent prospective study was designed to confirm the predictive utility of SB3.

    METHODS: SB3 immunohistochemistry was scored by previously validated criteria (score 0 = negative, score 1 = 1%-10% tumor cells positive, score 2 = 11%-50% tumor cells positive, and score 3 = >50% tumor cell positive) in 197 patients with stage IV NSCLC treated with PtC. This provided 80% power to detect a median survival increase from 150 days in patients with an SB3 immunohistochemistry score of 2 or more to 300 days in those with an SB3 score of 0 or 1.

    RESULTS: Thirty-six percent of NSCLCs stained positive for SB3. Median survival for SB3 negative/score 0 was 332 days, SB3 positive/score 1 was 268 days, and SB3 positive/score 2 or 3 was 120 days (p = 0.004). Cox proportional hazards analysis demonstrated that SB3 positivity is an independent predictor of survival (hazard ratio = 1.87; 95% confidence interval, 1.29-2.71; p = 0.001).The disease control rate in SB3 score 0, 1 = 65%, and score of 2 or more = 20 % (p = 0.002), with median survival 306 days (score 0, 1) versus 120 days (score ≥ 2, hazard ratio= 1.71; 95% confidence interval. 1.14-3.10; p = 0.002).

    CONCLUSIONS: SB3-positive immunohistochemistry score of 2 or more (>10% tumor cells positive) identifies a subgroup of patients with stage IV NSCLC who have a poor survival (median 120 days) when treated with PtC, similar to that estimated for untreated or chemo-refractory stage IV NSCLC. Further prospective qualification using biospecimens from randomized studies is needed, but SB3 seems to be a useful biomarker that identifies a highly resistant subgroup in whom PtC should be avoided.

    Original languageEnglish
    Pages (from-to)1502-1509
    Number of pages8
    JournalJournal of Thoracic Oncology
    Volume8
    Issue number12
    DOIs
    Publication statusPublished - Dec 2013

    Fingerprint

    Serpins
    Non-Small Cell Lung Carcinoma
    Biomarkers
    Drug Therapy
    Survival
    Platinum
    Immunohistochemistry
    Neoplasms
    Confidence Intervals
    Gene Expression Profiling

    Keywords

    • Adenocarcinoma
    • Adult
    • Aged
    • Antigens, Neoplasm
    • Antineoplastic Combined Chemotherapy Protocols
    • Carcinoma, Large Cell
    • Carcinoma, Non-Small-Cell Lung
    • Carcinoma, Squamous Cell
    • Female
    • Follow-Up Studies
    • Humans
    • Immunoenzyme Techniques
    • Lung Neoplasms
    • Male
    • Middle Aged
    • Neoplasm Staging
    • Prognosis
    • Prospective Studies
    • Serpins
    • Survival Rate
    • Tumor Markers, Biological

    Cite this

    Urquhart, Gordon ; Kerr, Keith M. ; Nicolson, Marianne ; Loo, Peh Sun ; Sharma, Ravi ; Shrimali, Raj ; Petty, Russell D. / Serpin B3 is associated with poor survival after chemotherapy and is a potential novel predictive biomarker in advanced non-small-cell lung cancer. In: Journal of Thoracic Oncology. 2013 ; Vol. 8, No. 12. pp. 1502-1509.
    @article{afec974088be4126a8c47753043fc465,
    title = "Serpin B3 is associated with poor survival after chemotherapy and is a potential novel predictive biomarker in advanced non-small-cell lung cancer",
    abstract = "INTRODUCTION: In a previous biomarker discovery project using gene-expression profiling we identified Serpin B3 (SB3) as a predictor of resistance to platinum doublet chemotherapy (PtC) in non-small-cell lung cancer (NSCLC). This independent prospective study was designed to confirm the predictive utility of SB3.METHODS: SB3 immunohistochemistry was scored by previously validated criteria (score 0 = negative, score 1 = 1{\%}-10{\%} tumor cells positive, score 2 = 11{\%}-50{\%} tumor cells positive, and score 3 = >50{\%} tumor cell positive) in 197 patients with stage IV NSCLC treated with PtC. This provided 80{\%} power to detect a median survival increase from 150 days in patients with an SB3 immunohistochemistry score of 2 or more to 300 days in those with an SB3 score of 0 or 1.RESULTS: Thirty-six percent of NSCLCs stained positive for SB3. Median survival for SB3 negative/score 0 was 332 days, SB3 positive/score 1 was 268 days, and SB3 positive/score 2 or 3 was 120 days (p = 0.004). Cox proportional hazards analysis demonstrated that SB3 positivity is an independent predictor of survival (hazard ratio = 1.87; 95{\%} confidence interval, 1.29-2.71; p = 0.001).The disease control rate in SB3 score 0, 1 = 65{\%}, and score of 2 or more = 20 {\%} (p = 0.002), with median survival 306 days (score 0, 1) versus 120 days (score ≥ 2, hazard ratio= 1.71; 95{\%} confidence interval. 1.14-3.10; p = 0.002).CONCLUSIONS: SB3-positive immunohistochemistry score of 2 or more (>10{\%} tumor cells positive) identifies a subgroup of patients with stage IV NSCLC who have a poor survival (median 120 days) when treated with PtC, similar to that estimated for untreated or chemo-refractory stage IV NSCLC. Further prospective qualification using biospecimens from randomized studies is needed, but SB3 seems to be a useful biomarker that identifies a highly resistant subgroup in whom PtC should be avoided.",
    keywords = "Adenocarcinoma, Adult, Aged, Antigens, Neoplasm, Antineoplastic Combined Chemotherapy Protocols, Carcinoma, Large Cell, Carcinoma, Non-Small-Cell Lung, Carcinoma, Squamous Cell, Female, Follow-Up Studies, Humans, Immunoenzyme Techniques, Lung Neoplasms, Male, Middle Aged, Neoplasm Staging, Prognosis, Prospective Studies, Serpins, Survival Rate, Tumor Markers, Biological",
    author = "Gordon Urquhart and Kerr, {Keith M.} and Marianne Nicolson and Loo, {Peh Sun} and Ravi Sharma and Raj Shrimali and Petty, {Russell D.}",
    year = "2013",
    month = "12",
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    language = "English",
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    pages = "1502--1509",
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    number = "12",

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    Serpin B3 is associated with poor survival after chemotherapy and is a potential novel predictive biomarker in advanced non-small-cell lung cancer. / Urquhart, Gordon; Kerr, Keith M.; Nicolson, Marianne; Loo, Peh Sun; Sharma, Ravi; Shrimali, Raj; Petty, Russell D. (Lead / Corresponding author).

    In: Journal of Thoracic Oncology, Vol. 8, No. 12, 12.2013, p. 1502-1509.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Serpin B3 is associated with poor survival after chemotherapy and is a potential novel predictive biomarker in advanced non-small-cell lung cancer

    AU - Urquhart, Gordon

    AU - Kerr, Keith M.

    AU - Nicolson, Marianne

    AU - Loo, Peh Sun

    AU - Sharma, Ravi

    AU - Shrimali, Raj

    AU - Petty, Russell D.

    PY - 2013/12

    Y1 - 2013/12

    N2 - INTRODUCTION: In a previous biomarker discovery project using gene-expression profiling we identified Serpin B3 (SB3) as a predictor of resistance to platinum doublet chemotherapy (PtC) in non-small-cell lung cancer (NSCLC). This independent prospective study was designed to confirm the predictive utility of SB3.METHODS: SB3 immunohistochemistry was scored by previously validated criteria (score 0 = negative, score 1 = 1%-10% tumor cells positive, score 2 = 11%-50% tumor cells positive, and score 3 = >50% tumor cell positive) in 197 patients with stage IV NSCLC treated with PtC. This provided 80% power to detect a median survival increase from 150 days in patients with an SB3 immunohistochemistry score of 2 or more to 300 days in those with an SB3 score of 0 or 1.RESULTS: Thirty-six percent of NSCLCs stained positive for SB3. Median survival for SB3 negative/score 0 was 332 days, SB3 positive/score 1 was 268 days, and SB3 positive/score 2 or 3 was 120 days (p = 0.004). Cox proportional hazards analysis demonstrated that SB3 positivity is an independent predictor of survival (hazard ratio = 1.87; 95% confidence interval, 1.29-2.71; p = 0.001).The disease control rate in SB3 score 0, 1 = 65%, and score of 2 or more = 20 % (p = 0.002), with median survival 306 days (score 0, 1) versus 120 days (score ≥ 2, hazard ratio= 1.71; 95% confidence interval. 1.14-3.10; p = 0.002).CONCLUSIONS: SB3-positive immunohistochemistry score of 2 or more (>10% tumor cells positive) identifies a subgroup of patients with stage IV NSCLC who have a poor survival (median 120 days) when treated with PtC, similar to that estimated for untreated or chemo-refractory stage IV NSCLC. Further prospective qualification using biospecimens from randomized studies is needed, but SB3 seems to be a useful biomarker that identifies a highly resistant subgroup in whom PtC should be avoided.

    AB - INTRODUCTION: In a previous biomarker discovery project using gene-expression profiling we identified Serpin B3 (SB3) as a predictor of resistance to platinum doublet chemotherapy (PtC) in non-small-cell lung cancer (NSCLC). This independent prospective study was designed to confirm the predictive utility of SB3.METHODS: SB3 immunohistochemistry was scored by previously validated criteria (score 0 = negative, score 1 = 1%-10% tumor cells positive, score 2 = 11%-50% tumor cells positive, and score 3 = >50% tumor cell positive) in 197 patients with stage IV NSCLC treated with PtC. This provided 80% power to detect a median survival increase from 150 days in patients with an SB3 immunohistochemistry score of 2 or more to 300 days in those with an SB3 score of 0 or 1.RESULTS: Thirty-six percent of NSCLCs stained positive for SB3. Median survival for SB3 negative/score 0 was 332 days, SB3 positive/score 1 was 268 days, and SB3 positive/score 2 or 3 was 120 days (p = 0.004). Cox proportional hazards analysis demonstrated that SB3 positivity is an independent predictor of survival (hazard ratio = 1.87; 95% confidence interval, 1.29-2.71; p = 0.001).The disease control rate in SB3 score 0, 1 = 65%, and score of 2 or more = 20 % (p = 0.002), with median survival 306 days (score 0, 1) versus 120 days (score ≥ 2, hazard ratio= 1.71; 95% confidence interval. 1.14-3.10; p = 0.002).CONCLUSIONS: SB3-positive immunohistochemistry score of 2 or more (>10% tumor cells positive) identifies a subgroup of patients with stage IV NSCLC who have a poor survival (median 120 days) when treated with PtC, similar to that estimated for untreated or chemo-refractory stage IV NSCLC. Further prospective qualification using biospecimens from randomized studies is needed, but SB3 seems to be a useful biomarker that identifies a highly resistant subgroup in whom PtC should be avoided.

    KW - Adenocarcinoma

    KW - Adult

    KW - Aged

    KW - Antigens, Neoplasm

    KW - Antineoplastic Combined Chemotherapy Protocols

    KW - Carcinoma, Large Cell

    KW - Carcinoma, Non-Small-Cell Lung

    KW - Carcinoma, Squamous Cell

    KW - Female

    KW - Follow-Up Studies

    KW - Humans

    KW - Immunoenzyme Techniques

    KW - Lung Neoplasms

    KW - Male

    KW - Middle Aged

    KW - Neoplasm Staging

    KW - Prognosis

    KW - Prospective Studies

    KW - Serpins

    KW - Survival Rate

    KW - Tumor Markers, Biological

    U2 - 10.1097/JTO.0000000000000016

    DO - 10.1097/JTO.0000000000000016

    M3 - Article

    VL - 8

    SP - 1502

    EP - 1509

    JO - Journal of Thoracic Oncology

    JF - Journal of Thoracic Oncology

    SN - 1556-0864

    IS - 12

    ER -