Objective:

To investigate whether plasma HERV-K env mRNA could serve as a minimally invasive biomarker for subtype-specific diagnosis and prognostic assessment in lung cancer.

Approach:

• Study Design: A retrospective single-center study enrolling 379 subjects, including patients with non-small cell lung cancer, malignant and benign pulmonary nodules, and healthy controls.
• Biomarker Quantification: HERV-K env mRNA was quantified in tumor tissues, paired adjacent tissues, and plasma using qRT-PCR.
• Statistical Analysis: Associations with clinicopathological variables, tissue-plasma concordance, correlations with serum tumor markers, ROC analysis, Kaplan-Meier survival, and multivariable Cox regression were analyzed.

Key Findings:

• HERV-K env mRNA was significantly upregulated in NSCLC tissues compared to paired adjacent tissues (P < 0.0001).
• Plasma HERV-K env mRNA levels were significantly elevated in lung cancer compared to benign nodules and healthy controls (P < 0.0001).
• Strong correlation between plasma and tissue expression of HERV-K env mRNA 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).
• High plasma HERV-K env mRNA was associated with poorer overall survival in LUAD (P = 0.035).

Interpretation:

Plasma HERV-K env mRNA captures a biologically plausible signal in LUAD.

Limitations:

• The study is retrospective and conducted at a single center.
• Broader clinical application and comparison with multi-marker panels require further validation.

Conclusion:

Plasma HERV-K env mRNA may serve as a novel biomarker for diagnosing LUAD and evaluating prognosis.