Interestingly, ROR1 may be re-induced during adult carcinogenesis. However, 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. ROR1 is normally expressed at high levels during development, becoming repressed in adult tissues. The structure of human ROR1 comprises one FZ (frizzled) domain, one Ig-like (immunoglobulin-like) C2-type domain, one kringle domain and one protein kinase domain. ROR1 belongs to the ROR receptor tyrosine kinase family, the only other known member of which is ROR2, with a 58% amino acid sequence coincidence. The receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an oncofoetal glycoprotein involved in differentiation, proliferation, migration and survival during the intrauterine development. 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. 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 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). ROR1 expression is independent of classical lung cancer molecular alterations and not correlated, in a Caucasian cohort, to TTF-1 expression.ĭespite 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. ROR1 overexpression could constitute a potential therapeutic target because altered in a consistent number of lung AC, especially in cases without druggable genetic alterations. 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. 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. 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.
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. This study aimed to assess the expression of ROR1 in lung adenocarcinoma (AC) patients. ROR1 was shown to inhibit apoptosis, potentiate EGFR signaling and reported to be overexpressed and associated with poor prognosis in several tumor models. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is normally detectable in embryonic tissues and absent in adult tissues.
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