İnvaziv duktal meme karsinomunda dolaşımdaki miR-6838-5p/miR-195-5p imzasının tanımlanması

Makaleler > Tam Makale · 2026

Yazarlar: Burçin KAYMAZ

MOLECULAR BIOLOGY REPORTS, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2026, cilt 53, ss 1-14

DOI: 10.1007/s11033-026-12762-2

Özet

<p>Background&nbsp;Circulating&nbsp;miRNAs&nbsp;(c-miRNAs)&nbsp;are&nbsp;promising&nbsp;non-invasive&nbsp;biomarkers&nbsp;for&nbsp;breast&nbsp;cancer&nbsp;detection,&nbsp;but&nbsp;</p><p>reproducible&nbsp;signatures&nbsp;remain&nbsp;limited.&nbsp;This&nbsp;study&nbsp;aimed&nbsp;to&nbsp;identify&nbsp;a&nbsp;circulating&nbsp;miRNA&nbsp;signature&nbsp;for&nbsp;invasive&nbsp;ductal&nbsp;breast&nbsp;</p><p>carcinoma,&nbsp;evaluate&nbsp;its&nbsp;discriminatory&nbsp;performance&nbsp;in&nbsp;an&nbsp;independent&nbsp;serum&nbsp;cohort,&nbsp;and&nbsp;explore&nbsp;the&nbsp;biological&nbsp;context&nbsp;of&nbsp;</p><p>the&nbsp;selected&nbsp;c-miRNAs.</p><p>Methods&nbsp;and&nbsp;Results&nbsp;Serum&nbsp;expression&nbsp;of&nbsp;21&nbsp;candidate&nbsp;c-miRNAs&nbsp;was&nbsp;analyzed&nbsp;by&nbsp;RT-qPCR&nbsp;in&nbsp;46&nbsp;treatment-naive&nbsp;inva-</p><p>sive&nbsp;ductal&nbsp;breast&nbsp;carcinoma&nbsp;patients&nbsp;and&nbsp;46&nbsp;healthy&nbsp;controls.&nbsp;Whole-blood&nbsp;expression&nbsp;of&nbsp;immune&nbsp;checkpoint-related&nbsp;genes&nbsp;</p><p>(PDCD1,&nbsp;CD274,&nbsp;CTLA4,&nbsp;and&nbsp;LAG3)&nbsp;was&nbsp;also&nbsp;assessed&nbsp;in&nbsp;50&nbsp;patients&nbsp;and&nbsp;46&nbsp;controls.&nbsp;Among&nbsp;the&nbsp;21&nbsp;candidates,&nbsp;12&nbsp;</p><p>c-miRNAs&nbsp;were&nbsp;significantly&nbsp;dysregulated&nbsp;after&nbsp;FDR&nbsp;correction.&nbsp;miR-6838-5p&nbsp;and&nbsp;miR-195-5p&nbsp;showed&nbsp;the&nbsp;strongest&nbsp;dis-</p><p>criminatory&nbsp;performance&nbsp;and&nbsp;were&nbsp;combined&nbsp;into&nbsp;a&nbsp;two-miRNA&nbsp;logistic&nbsp;regression&nbsp;model.&nbsp;This&nbsp;model&nbsp;achieved&nbsp;an&nbsp;AUC&nbsp;of&nbsp;</p><p>0.923&nbsp;(95%&nbsp;CI:&nbsp;0.873–0.974)&nbsp;in&nbsp;the&nbsp;discovery&nbsp;cohort&nbsp;and&nbsp;an&nbsp;optimism-corrected&nbsp;AUC&nbsp;of&nbsp;0.917&nbsp;after&nbsp;1,000&nbsp;bootstrap&nbsp;itera-</p><p>tions.&nbsp;In&nbsp;the&nbsp;independent&nbsp;GSE73002&nbsp;serum&nbsp;cohort,&nbsp;including&nbsp;1,280&nbsp;breast&nbsp;cancer&nbsp;patients&nbsp;and&nbsp;2,684&nbsp;non-cancer&nbsp;controls,&nbsp;the&nbsp;</p><p>same&nbsp;two-miRNA&nbsp;combination&nbsp;retained&nbsp;strong&nbsp;ROC-derived&nbsp;discriminatory&nbsp;performance&nbsp;with&nbsp;an&nbsp;AUC&nbsp;of&nbsp;0.939&nbsp;(95%&nbsp;CI:&nbsp;</p><p>0.930–0.948).&nbsp;Exploratory&nbsp;downstream&nbsp;analyses&nbsp;provided&nbsp;additional&nbsp;biological&nbsp;context.</p><p>Conclusions&nbsp;The&nbsp;miR-6838-5p/miR-195-5p&nbsp;combination&nbsp;represents&nbsp;a&nbsp;promising&nbsp;circulating&nbsp;miRNA&nbsp;signature&nbsp;for&nbsp;invasive&nbsp;</p><p>ductal&nbsp;breast&nbsp;carcinoma.&nbsp;Its&nbsp;consistent&nbsp;discriminatory&nbsp;performance&nbsp;in&nbsp;the&nbsp;discovery&nbsp;cohort&nbsp;and&nbsp;an&nbsp;independent&nbsp;serum&nbsp;cohort&nbsp;</p><p>supports&nbsp;further&nbsp;evaluation&nbsp;in&nbsp;larger&nbsp;prospective&nbsp;studies.&nbsp;Additional&nbsp;work&nbsp;in&nbsp;clinically&nbsp;diverse&nbsp;cohorts,&nbsp;including&nbsp;benign&nbsp;</p><p>breast&nbsp;disease&nbsp;and&nbsp;early-stage&nbsp;populations,&nbsp;as&nbsp;well&nbsp;as&nbsp;paired&nbsp;serum–tissue&nbsp;and&nbsp;functional&nbsp;validation&nbsp;studies,&nbsp;is&nbsp;needed&nbsp;to&nbsp;</p><p>define&nbsp;its&nbsp;clinical&nbsp;applicability&nbsp;and&nbsp;biological&nbsp;origin.</p><p>Keywords&nbsp;Breast&nbsp;cancer&nbsp;·&nbsp;Invasive&nbsp;ductal&nbsp;carcinoma&nbsp;·&nbsp;Circulating&nbsp;microRNAs&nbsp;·&nbsp;miR-6838-5p&nbsp;·&nbsp;miR-195-5p&nbsp;·&nbsp;Two-</p><p>miRNA&nbsp;signature&nbsp;·&nbsp;Liquid&nbsp;biopsy</p>

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