{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T14:44:36Z","timestamp":1782917076026,"version":"3.54.5"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Early detection of lung adenocarcinoma (LUAD) remains challenging because low-dose computed tomography produces many false-positive pulmonary nodules and conventional serum tumor markers show histology-dependent diagnostic performance. We investigated whether plasma HERV-K env mRNA could serve as a minimally invasive biomarker for subtype-specific diagnosis and prognostic assessment in lung cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective single-center study enrolled 379 subjects, including 249 patients with non-small cell lung cancer (162 LUAD and 87 lung squamous cell carcinoma [LUSC]), 30 patients with malignant pulmonary nodules, 50 patients with benign pulmonary nodules, and 50 healthy controls. HERV-K env mRNA was quantified in tumor tissues, paired adjacent tissues, and EDTA-anticoagulated plasma by qRT-PCR. Associations with clinicopathological variables, tissue-plasma concordance, correlations with conventional serum tumor markers, ROC diagnostic performance, Kaplan-Meier survival, and multivariable Cox regression were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>HERV-K env mRNA was significantly upregulated in NSCLC tissues versus paired adjacent tissues (P &amp;lt; 0.0001) and was higher in LUAD than in LUSC (P &amp;lt; 0.0001). Tissue expression increased with advanced T stage, lymph node metastasis, and higher TNM stage (all P &amp;lt; 0.0001). Plasma HERV-K env mRNA levels were significantly elevated in lung cancer compared with benign pulmonary nodules and healthy controls (P &amp;lt; 0.0001) and correlated strongly with tissue expression in both LUSC (r = 0.9025) and LUAD (r = 0.7305). ROC analysis showed excellent performance for stage I\/II LUAD versus healthy controls (AUC = 0.914), moderate performance for malignant pulmonary nodules versus healthy controls (AUC = 0.758), but limited performance for early-stage LUSC (AUC = 0.505). Plasma HERV-K env mRNA showed no significant correlations with conventional serum tumor markers. High plasma HERV-K env mRNA was associated with poorer overall survival in LUAD (P = 0.035), and multivariable Cox regression supported independent prognostic value in the overall cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Plasma HERV-K env mRNA captures a biologically plausible and analytically non-redundant signal with the strongest current clinical promise in LUAD rather than LUSC. Its LUAD performance appears competitive with published single-marker serum assays, but broader clinical application and comparison with optimized conventional multi-marker panels require prospective multicenter and same-cohort validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1782414","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T13:52:15Z","timestamp":1782913935000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Plasma HERV-K envelopE RNA: a minimally invasive biomarker for lung adenocarcinoma detection and prognostic assessment in the context of conventional serum tumor markers"],"prefix":"10.3389","volume":"17","author":[{"given":"Fan","family":"Bu","sequence":"first","affiliation":[{"name":"Zhejiang Cancer Institute, Zhejiang Cancer Hospital","place":["Hangzhou, Zhejiang, China"]},{"name":"The Second Clinical Medical College of Zhejiang 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