Novel Transcriptional and DNA Methylation Abnormalities of SORT1 Gene in Non-Small Cell Lung Cancer.

Acha-Sagredo, Amelia, Wilson, Cornelia M, Garcia Bediaga, Naiara, Kalirai, Helen ORCID: 0000-0002-4440-2576, Davies, Michael PA ORCID: 0000-0002-7609-4977, Coupland, Sarah E ORCID: 0000-0002-1464-2069, Field, John K ORCID: 0000-0003-3951-6365 and Liloglou, Triantafillos ORCID: 0000-0003-0460-1404 (2024) Novel Transcriptional and DNA Methylation Abnormalities of SORT1 Gene in Non-Small Cell Lung Cancer. Cancers, 16 (11). p. 2154. ISSN 2072-6694, 2072-6694

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Abstract

Sortilin is an important regulator with potential tumour-suppressor function by limiting EGFR signalling. In this study, we undertook a comprehensive expression analysis of sortilin transcript variants and the DNA methylation status of their corresponding promoters in human non-small cell carcinomas (NSCLCs). RNA/DNA was extracted from 81 NSCLC samples and paired normal tissue. mRNA expression was measured by qPCR and DNA methylation determined by pyrosequencing. BigDye-terminator sequencing was used to confirm exon-8 alternative splicing. Results demonstrated that both SORT1A and SORT1B variants were downregulated in lung tumours. The SORT1A/SORT1B expression ratio was higher in tumours compared to normal tissue. SORT1B promoter hypermethylation was detected in lung tumours compared to normal lung (median difference 14%, Mann-Whitney test p = 10^-6). Interestingly, SORT1B is hypermethylated in white blood cells, but a small and very consistent drop in methylation (6%, p = 10^-15) was observed in the lung cancer cases compared to control subjects. We demonstrate that the SORT1B exon-8 splice variation, reported in sequence databases, is also a feature of SORT1A. The significantly altered quantitative and qualitative characteristics of sortilin mRNA in NSCLC indicate a significant involvement in tumour pathogenesis and may have significant impact for its utility as a predictive marker in lung cancer management.

Item Type:	Article
Uncontrolled Keywords:	sortilin, non-small cell lung cancer, DNA methylation, splicing
Divisions:	Faculty of Health & Life Sciences Faculty of Health & Life Sciences > Inst. Life Courses & Medical Sciences Faculty of Health & Life Sciences > Inst. Systems, Molec & Integrative Biology > Inst. Systems, Molec & Integrative Biology
Depositing User:	Symplectic Admin
Date Deposited:	14 Oct 2024 09:41
Last Modified:	28 Feb 2026 01:05
DOI:	10.3390/cancers16112154
Related Websites:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3185064
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