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

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

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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
  • non-small-cell lung
  • 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

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.

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

Research output: Contribution to journalArticle

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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, non-small-cell lung, 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",
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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

KW - neoplasm

KW - antineoplastic combined chemotherapy protocols

KW - carcinoma

KW - large cell

KW - non-small-cell lung

KW - 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

KW - biological

U2 - 10.1097/JTO.0000000000000016

DO - 10.1097/JTO.0000000000000016

M3 - Article

C2 - 24389432

VL - 8

SP - 1502

EP - 1509

JO - Journal of Thoracic Oncology

JF - Journal of Thoracic Oncology

SN - 1556-0864

IS - 12

ER -