Functional and clinical significance of ROR1 in lung adenocarcinoma

Giovanna Schiavone,Vittoria Martin,Milo Frattini,Francesca Molinari,Luciano Wannesson,Samantha Epistolio,Jessica Barizzi,Luca Mazzucchelli

doi:10.1186/s12885-020-07587-6

Giovanna Schiavone, Vittoria Martin + Show 6 more

Open Access

https://doi.org/10.1186/s12885-020-07587-6

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Abstract

BackgroundReceptor tyrosine kinase-like orphan receptor 1 (ROR1) is normally detectable in embryonic tissues and absent in adult tissues. ROR1 was shown to inhibit apoptosis, potentiate EGFR signaling and reported to be overexpressed and associated with poor prognosis in several tumor models. This study aimed to assess the expression of ROR1 in lung adenocarcinoma (AC) patients.MethodsWe analyzed ROR1 expression by quantitative real-time PCR (qRT-PCR) in 56 histologically confirmed lung AC, stage I to IV, in addition we evaluated its association with TTF-1 (thyroid transcription factor-1) expression and the main molecular alterations involved in lung cancerogenesis.ResultsROR1 overexpression was observed in 28.6% of the entire cohort, using a cut-off of 1, or in 51.8% of the cases using the median value as threshold. Among patients without any genetic alteration, ROR1 overexpression was observed in 34.8% considering a cut-off of 1 and 52.2% considering the median value. The distribution of ROR1 was homogeneous among the different molecular categories: we found no association of ROR1 expression and the presence of gene mutations/rearrangements or the expression of TTF-1.ConclusionsROR1 overexpression could constitute a potential therapeutic target because altered in a consistent number of lung AC, especially in cases without druggable genetic alterations. ROR1 expression is independent of classical lung cancer molecular alterations and not correlated, in a Caucasian cohort, to TTF-1 expression.

Highlights

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is normally detectable in embryonic tissues and absent in adult tissues
The level of ROR1 overexpression, assessed both by the cut-off value (r > 1 vs r ≤ 1) (Fig. 1a, b and c) and the median one (Fig. 2a, b and c) was not associated with overall survival (OS) and this observation was independent of the tumor stage
Among our patients without a genetic alteration, we found ROR1 overexpression in 34.8 and 52.2%, defined by r = 1 and a value over the median level of expression, respectively

Summary

Introduction

Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is normally detectable in embryonic tissues and absent in adult tissues. This study aimed to assess the expression of ROR1 in lung adenocarcinoma (AC) patients. Lung AC has been extensively characterized, but the enormous body of studies has led to the identification of only a subgroup of patients The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofoetal glycoprotein involved in differentiation, proliferation, migration and survival during the intrauterine development. ROR1 is normally expressed at high levels during development, becoming repressed in adult tissues. A low level of ROR1 expression is seen in adipose tissue and, to a lesser degree, in pancreas, lung and a subset of B cell leukemia [6, 7]

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