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MicroRNA Based Liquid Biopsy: The Experience of the Plasma miRNA Signature Classifier MSC for Lung Cancer Screening
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Smoking-dependent circulating non-coding biomarkers in lung cancer.

Abdullah Farasani1

  • 1Department of Medical Laboratory Technology, Faculty of Nursing and Health Sciences, Jazan University, Jazan 45142, Saudi Arabia; Health Research Centre, Jazan University, Jazan, Saudi Arabia.

Clinica Chimica Acta; International Journal of Clinical Chemistry
|February 20, 2026
PubMed
Summary

Smoking impacts lung cancer progression and circulating nucleic acids. This review explores how smoking dependence affects circulating non-coding RNAs (ncRNAs) for better liquid biopsy interpretation in lung cancer detection and monitoring.

Keywords:
Biomarker validationCirculating non-coding RNAsExtracellular vesicles (exosomes)LncRNAsSmoking-related lung cancercircRNAsmiRNAs

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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.