{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T14:09:16Z","timestamp":1768918156755,"version":"3.49.0"},"reference-count":64,"publisher":"PeerJ","license":[{"start":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T00:00:00Z","timestamp":1702339200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Gene mutations can contribute to lung adenocarcinoma (LUAD) development, metastasis, and therapy. This study aims to identify mutations in the endothelial nitric oxide synthase (<jats:italic>eNOS<\/jats:italic> or <jats:italic>NOS3<\/jats:italic>) and cystathionine <jats:italic>\u03b3<\/jats:italic>-lyase (<jats:italic>CSE<\/jats:italic> or <jats:italic>CTH<\/jats:italic>) genes that are connected to LUAD symptoms. Two gene polymorphisms were identified using Sanger sequencing in 31 LUAD patients\u2019 formalin-fixed paraffin-embedded (FFPE) tissues. Epidermal growth factor receptor (EGFR) mutation and programmed death-ligand 1 (PD-L1) expression were examined in 110 LUAD patients using real-time polymerase chain reaction and immunohistochemistry. Mutations in the selected genes were retrieved from the gnomAD database for all cancer types and the Mutagene and COSMIC databases for LUAD patients. The GeneMANIA prediction server was used to predict the interaction between the studied genes. Poorly and moderately differentiated tumours predominated, with pT3 N2 Mx being the most prevalent stage. Polymorphism data showed 189 <jats:italic>NOS3<\/jats:italic> gene mutations and 34 <jats:italic>CTH<\/jats:italic> gene mutations. In 110 LUAD patients, 14 (12.73%) were PD-L1 positive and expressed 50% or more protein. Eight (7.27%) samples included EGFR mutations, including two deletions and two point mutations in exon 19, four point mutations in exon 21. In gnomAD, 4012 <jats:italic>NOS3<\/jats:italic> mutations and 1214 <jats:italic>CTH<\/jats:italic> mutations are present. In the Mutagene and COSMIC databases, the <jats:italic>NOS3<\/jats:italic> gene had 295 and 93 mutations, whereas the <jats:italic>CTH<\/jats:italic> gene had 61 and 36. According to the GeneMANIA prediction server, 10 genes are related to <jats:italic>NOS3<\/jats:italic>, eight with <jats:italic>CTH<\/jats:italic>, 15 with <jats:italic>EGFR<\/jats:italic>, and 5 with <jats:italic>PD<\/jats:italic>-L1. This study is the first to identify several previously unknown mutations in LUAD patients\u2019 <jats:italic>NOS3<\/jats:italic> and <jats:italic>CTH<\/jats:italic> genes, with potential therapeutic implications.<\/jats:p>","DOI":"10.7717\/peerj.16209","type":"journal-article","created":{"date-parts":[[2023,12,12]],"date-time":"2023-12-12T08:43:39Z","timestamp":1702370619000},"page":"e16209","source":"Crossref","is-referenced-by-count":6,"title":["NOS3 and CTH gene mutations as new molecular markers for detection of lung adenocarcinoma"],"prefix":"10.7717","volume":"11","author":[{"given":"Iman","family":"Abdullah Ramadhan","sequence":"first","affiliation":[{"name":"Department of Biology, College of Science, Salahaddin University-Erbil, Erbil, Kurdistan Region, Iraq"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luqman","family":"Rahman Sulaiman","sequence":"additional","affiliation":[{"name":"Department of Medicine, College of Medicine, Hawler Medical University, 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