Immunohistochemical validation study of 15-gene biomarker panel predictive of benefit from adjuvant chemotherapy in resected non-small-cell lung cancer: analysis of JBR.10

ESMO Open

article

Stacy Grieve¹  Keyue Ding²  Jonathan Moore³  Mathew Finniss³  Ayush Ray¹  Miranda Lees¹  Faisal Hossain¹  Alli Murugesan¹  Jane Agar⁴  Cenk Acar⁴  James Taylor²  Frances A. Shepherd⁵  Tony Reiman¹ 

[1] Department of Biology, University of New Brunswick Saint John;Canadian Cancer Trials Group;Department of Medicine, Dalhousie University;Department of Pathology, Saint John Regional Hospital;Department of Medical Oncology and Hematology, Princess Margaret Hospital Cancer Centre, University of Toronto

关键词: non-small-cell lung cancer;    immunohistochemistry;    gene expression profile;    biomarker;    predictive;    adjuvant chemotherapy;   

DOI  :  10.1136/esmoopen-2020-000679

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Objective There are no validated approaches to predictbenefit from adjuvant chemotherapy for resected patientswith non-small-cell lung cancer (NSCLC). The aim ofthis study was to translate a 15-gene mRNA expressionprofile published by Zhu et al, shown to be prognosticand predictive of benefit, into a readily applicableimmunohistochemistry (IHC) panel.Methods For seven of the genes in the gene expressionprofile (GEP) for which suitable commercial antibodieswere available, we semiquantitatively assessed the IHCexpression and prognostic significance for 173 patientstreated at the Saint John Regional Hospital (SJRH). Cutoffs for high and low expression were defined for eachmarker and applied to IHC scores from 291 of the 482patients in JBR.10, including patients on both the adjuvantchemotherapy and observation arms. The prognostic andpredictive value of these markers on overall survival (OS)or recurrence-free survival (RFS) was assessed by Coxregression models.Results In the SJRH cohort, in 62 patients with resectedstage II–III NSCLC, the prognostic significance of IHCassays for four proteins were concordant with Zhu’sGEP results. Low FOSL2 (OS, HR=0.15; p=0.0001; RFS,HR=0.14; p<0.0001) and high STMN2 (RFS, HR=2.501;p=0.0197) were adverse prognostic factors. Low ATP1B1and low TRIM14 expression trended toward worse OS andRFS. Validation of these markers with JBR.10 patientsfailed to show prognostic significance either individuallyor in combined risk classifications. Additionally, theinteraction between these markers and chemotherapytreatment in predicting OS (FOSL2, p=0.52; STMN2p=0.14; ATP1B1, p=0.33; TRIM14, p=0.81) or RFS (FOSL2,p=0.63; STMN2, p=0.12; ATP1B1, p=0.66; TRIM14,p=0.57) did not reach significance, individually or incombination panels.Conclusions Zhu’s GEP could not be translatedinto an IHC panel predictive of benefit from adjuvantchemotherapy. Future predictive biomarker analysis inthe adjuvant NSCLC setting may need to focus on noveltherapies.

【 授权许可】

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