{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:55:06Z","timestamp":1791370506394,"version":"4.3.1"},"reference-count":141,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100019286","name":"Ajman University","doi-asserted-by":"publisher","award":["AU\u2010DRG 501\/2025"],"award-info":[{"award-number":["AU\u2010DRG 501\/2025"]}],"id":[{"id":"10.13039\/501100019286","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"abstract":"<jats:p>\n                    Hereditary nonpolyposis colorectal cancer (HNPCC), usually termed Lynch syndrome (LS), is the most prevalent hereditary colorectal cancer syndrome, yet molecular biomarkers to differentiate nonmalignant from malignant LS cases remain limited. We performed a secondary analysis of the circulating miRNAome in 155 individuals, including healthy controls (CTRL), nonmalignant LS (H\u2010LS), cancer\u2010associated LS (C\u2010LS), and sporadic colorectal cancer (CRC). We observed that LS variant heterozygotes, especially those without overt cancer, exhibit a transitional miRNAomic architecture distinct from both healthy controls and CRC patients in different age groups. Age\u2010stratified differential expression and miRNA\u2010mRNA network analyses revealed distinct regulatory hubs across groups. Group\u2010specific miRNAs targeted oncogenic, immune, and DNA repair pathways. The analysis suggested that nonmalignant LS variant heterozygotes occupy a circulating miRNAome state distinct from both healthy controls and overt CRC, whereas C\u2010LS and sporadic CRC shared selected malignant\u2010associated miRNA features. To assess external concordance, we performed orthogonal validation of a prespecified six\u2010miRNA panel in the independent\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.ncbi.nlm.nih.gov\/geo\/query\/acc.cgi?acc=GSE30454\">GSE30454<\/jats:ext-link>\n                    primary colorectal tissue cohort, comprising normal, LS, sporadic MSI, and MSS samples. The composite panel preserved disease\u2010axis structure across the external cohort, with strongest discrimination in biologically relevant mismatch repair\u2010related contrasts. These findings suggest candidate circulating miRNA molecular states across LS and sporadic colorectal cancer.\n                  <\/jats:p>","DOI":"10.1002\/1878-0261.70338","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T10:39:23Z","timestamp":1791369563000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unique circulating\n                    <scp>miRNAome<\/scp>\n                    signatures captured with distinct molecular states in Lynch syndrome and sporadic colorectal cancer"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8794-604X","authenticated-orcid":false,"given":"Ramadhani Salum","family":"Chambuso","sequence":"first","affiliation":[{"name":"Department of Pathological Sciences, College of Medicine Ajman University  UAE"},{"name":"Department of Global Health and Population Harvard T.H. 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