{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:09:49Z","timestamp":1760144989167,"version":"build-2065373602"},"reference-count":30,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T00:00:00Z","timestamp":1717632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"North West Cancer Research","award":["1065\/2018","2017\/02\/Liloglou"],"award-info":[{"award-number":["1065\/2018","2017\/02\/Liloglou"]}]},{"name":"Roy Castle Lung Cancer Foundation","award":["1065\/2018","2017\/02\/Liloglou"],"award-info":[{"award-number":["1065\/2018","2017\/02\/Liloglou"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>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\u2013Whitney test p = 10\u22126). Interestingly, SORT1B is hypermethylated in white blood cells, but a small and very consistent drop in methylation (6%, p = 10\u221215) 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.<\/jats:p>","DOI":"10.3390\/cancers16112154","type":"journal-article","created":{"date-parts":[[2024,6,6]],"date-time":"2024-06-06T03:44:35Z","timestamp":1717645475000},"page":"2154","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Novel Transcriptional and DNA Methylation Abnormalities of SORT1 Gene in Non-Small Cell Lung Cancer"],"prefix":"10.3390","volume":"16","author":[{"given":"Amelia","family":"Acha-Sagredo","sequence":"first","affiliation":[{"name":"Institute of Systems, Molecular & Integrative Biology, University of Liverpool, Liverpool L69 3BX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6584-6179","authenticated-orcid":false,"given":"Cornelia M.","family":"Wilson","sequence":"additional","affiliation":[{"name":"Life Sciences Industry Liaison Lab, School of Psychology and Life Sciences, Canterbury Christ Church University, Canterbury CT1 1QU, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naiara","family":"Garcia Bediaga","sequence":"additional","affiliation":[{"name":"Adelaide Centre for Epigenetics, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Helen","family":"Kalirai","sequence":"additional","affiliation":[{"name":"Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7609-4977","authenticated-orcid":false,"given":"Michael P. 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