Smoking-dependent circulating non-coding biomarkers in lung cancer

Area of Science:

• Oncology
• Molecular Biology
• Biomarkers

Background:

• Smoking is a primary cause of lung cancer, affecting tumor development and circulating nucleic acids.
• Interpreting liquid biopsy signals in smokers requires specialized approaches due to altered nucleic acid profiles.
• Circulating non-coding RNAs (ncRNAs) show promise as biomarkers for lung cancer detection, prognosis, and treatment monitoring.

Purpose of the Study:

• To review and integrate evidence on smoking dependence patterns across lung cancer subtypes.
• To correlate smoking exposure and comorbidities with circulating RNA profiles for biomarker informativeness.
• To examine the laboratory implementation and analytical/clinical trade-offs of cell-free vs. extracellular vesicle (EV)-associated ncRNAs.

Main Methods:

• Comprehensive literature search of PubMed and Scopus databases (2010-2025).
• Integration of existing evidence with current review findings.
• Correlation of smoking exposure measures and comorbidities with circulating RNA profiles.
• Discussion of laboratory pre-analytics, normalization, platform selection, and risk score reporting.

Main Results:

• Circulating ncRNAs (miRNAs, lncRNAs) are associated with early detection, histologic differentiation, survival outcomes, and treatment response in lung cancer.
• Smoking dependence influences circulating RNA profiles, impacting biomarker utility.
• Cell-free and EV-associated ncRNAs have distinct analytical and clinical characteristics, with EVs offering potential incremental value.

Conclusions:

• Understanding smoking's impact on circulating RNA profiles is crucial for effective liquid biopsy interpretation in lung cancer.
• Standardized laboratory practices and multicenter validation are essential for clinical application of ncRNA biomarkers.
• ncRNAs hold potential for various clinical applications, including indeterminate nodule triage and treatment monitoring.