Functional and clinical significance of ROR1 in lung adenocarcinoma
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RESEARCH ARTICLE
Open Access
Functional and clinical significance of ROR1 in lung adenocarcinoma Schiavone Giovanna1*†, Epistolio Samantha2†, Martin Vittoria2, Molinari Francesca2, Barizzi Jessica2, Mazzucchelli Luca2, Frattini Milo2† and Wannesson Luciano1†
Abstract Background: Receptor 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. Methods: We 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. Results: ROR1 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. Conclusions: ROR1 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. Keywords: Non-small cell lung cancer, ROR1, Targeted therapies, Overall survival, EGFR
Background Despite several major achievements in the field of targeted and immune treatments for advanced non-small cell lung cancer (NSCLC), especially for the adenocarcinoma (AC) subgroup, this disease still represents a leading cause of death in Europe and worldwide [1]. At a molecular level, lung AC has been extensively characterized, but the enormous body of studies has led to the identification of only a subgroup of patients (cumulatively encompassing no more * Correspondence: [email protected] † Schiavone Giovanna and Epistolio Samantha are co-first authors † Frattini Milo and are Wannesson, Luciano are co-senior authors 1 Istituto Oncologico della Svizzera Italiana, Via Ospedale, 6500 Bellinzona, Switzerland Full list of author information is available at the end of the article
than 25% of cases) who have a molecular profile favorable to the efficacy of targeted therapies (i.e.: those carrying either EGFR mutations, or ALK, ROS1 or RET gene rearrangements) [2, 3]. Therefore, the identification of new molecular alterations and the development and application of related targeted strategies is essential to improve the prognosis of this disease. The
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