HER-3 Expression and MEK Activation in Non-small Cell Lung Cancer
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Authors
Manickavasagar, T
Yuan, W
Carreira, S
Gurel, B
Miranda, S
Ferreira, A
Crespo, M
Riisnaes, R
Baker, C
O’Brien, M
Bhosle, J
Popat, S
Banerji, U
Lopez, J
Bono, JD
Minchom, A
Yuan, W
Carreira, S
Gurel, B
Miranda, S
Ferreira, A
Crespo, M
Riisnaes, R
Baker, C
O’Brien, M
Bhosle, J
Popat, S
Banerji, U
Lopez, J
Bono, JD
Minchom, A
Document Type
Journal Article
Date
2020-08-26
Date Accepted
2021-02-22
Abstract
<title>Abstract</title> <p>BackgroundHER-3 has a role in pathogenesis and development of resistance to targeted therapies in non-small cell lung cancer (NSCLC). MethodsWe analysed tumour samples from 45 patients with adenocarcinoma of the lung. HER-3 and HER-2 expression was identified using immunohistochemistry as well as bioinformatic interrogation of The Cancer Genome Atlas (TGCA). ResultsHER-3 was highly expressed in 42.2% of cases and observed more frequently than HER-2 overexpression. <italic>ERBB3</italic> copy number alone did not account for HER-3 overexpression. Bioinformatic analysis of TCGA demonstrated that MEK activity score (a score of downstream pathway activity and surrogate of functional HER-3 signalling) did not correlate with HER-3 ligands. EGFR pathway signalling was predominant with a significantly positive correlation of <italic>EGFR</italic> and <italic>AREG</italic> expression with MEK activity score. In the ERBB3 expressed group, <italic>ERBB3</italic> RNA expression levels were significantly correlated with MEK activity score. <italic>ERBB3</italic> expression level remained highly positively correlated with MEK activity after adjusting for <italic>EGFR</italic> expression. ConclusionHER-3 expression is common and it is not associated with gene amplification nor is it ligand dependent. HER-3 is an alternative pathway to EGFR activating MEK. HER-3 is a potential therapeutic target in NSCLC by virtue of frequent overexpression and functional downstream signalling.</p>
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Cancer Biomarkers
Cancer Biomarkers
Cancer Biomarkers