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Background <p>Lung cancer remains a leading cause of cancer-related mortality worldwide, in part because reliable, minimally invasive tools for timely diagnosis are still limited. Serum biomarkers have emerged as promising candidates for non-invasive diagnostic assessment, but their clinical value remains incompletely defined.</p> Methods <p>We conducted a systematic review of PubMed, Scopus, and Web of Science on June 22, 2024, without language restrictions, to identify studies published between 2019 and 2023. Eligible studies evaluated serum biomarkers for lung cancer diagnosis using laboratory-based assays. We excluded non-original articles, studies based on non-serum specimens, purely machine-learning–driven analyses, and non-English reports. Study quality was appraised using QUADAS-2. Diagnostic performance metrics, including sensitivity, specificity, and area under the receiver operating characteristic curve (AUC), were extracted for key biomarkers.</p> Results <p>Fifty-six studies met the inclusion criteria. In non-small cell lung cancer (NSCLC), multi-marker microRNA (miRNA) panels—particularly those incorporating miR-21-5p, miR-141-3p, miR-222-3p, and miR-486-5p—demonstrated strong diagnostic performance (AUC = 0.96). Alpha-1B tubulin showed exceptional discriminative ability for lung adenocarcinoma (LUAD) (AUC = 0.99). In small cell lung cancer (SCLC), neuron-specific enolase (NSE) remained a clinically relevant biomarker with appreciable diagnostic potential. In addition, miR-1268b and miR-6075 exhibited excellent performance across lung cancer subtypes (AUC = 0.99).</p> Conclusions <p>Serum biomarkers show substantial promise for the diagnostic assessment of lung cancer, particularly within subtype-specific contexts. However, methodological heterogeneity, variability in study populations, and limited standardization of assay protocols continue to constrain clinical translation. Well-designed prospective studies with standardized methodologies are needed to validate these biomarkers and clarify their role in routine diagnostic practice.</p>

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Diagnostic Performance of Serum Biomarkers in Lung Cancer: A Systematic Review

  • 期刊论文

  • 发表日期：

    2026年6月30日

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  • Mahdieh Jafari Nodoushan,
  • Safiyehsadat Heydari,
  • Marzieh Lotfi,
  • Seyedeh Mahdieh Namayandeh,
  • Mohammadali Didehban,
  • Seyed Hossein Shahcheraghi

摘要

Background

Lung cancer remains a leading cause of cancer-related mortality worldwide, in part because reliable, minimally invasive tools for timely diagnosis are still limited. Serum biomarkers have emerged as promising candidates for non-invasive diagnostic assessment, but their clinical value remains incompletely defined.

Methods

We conducted a systematic review of PubMed, Scopus, and Web of Science on June 22, 2024, without language restrictions, to identify studies published between 2019 and 2023. Eligible studies evaluated serum biomarkers for lung cancer diagnosis using laboratory-based assays. We excluded non-original articles, studies based on non-serum specimens, purely machine-learning–driven analyses, and non-English reports. Study quality was appraised using QUADAS-2. Diagnostic performance metrics, including sensitivity, specificity, and area under the receiver operating characteristic curve (AUC), were extracted for key biomarkers.

Results

Fifty-six studies met the inclusion criteria. In non-small cell lung cancer (NSCLC), multi-marker microRNA (miRNA) panels—particularly those incorporating miR-21-5p, miR-141-3p, miR-222-3p, and miR-486-5p—demonstrated strong diagnostic performance (AUC = 0.96). Alpha-1B tubulin showed exceptional discriminative ability for lung adenocarcinoma (LUAD) (AUC = 0.99). In small cell lung cancer (SCLC), neuron-specific enolase (NSE) remained a clinically relevant biomarker with appreciable diagnostic potential. In addition, miR-1268b and miR-6075 exhibited excellent performance across lung cancer subtypes (AUC = 0.99).

Conclusions

Serum biomarkers show substantial promise for the diagnostic assessment of lung cancer, particularly within subtype-specific contexts. However, methodological heterogeneity, variability in study populations, and limited standardization of assay protocols continue to constrain clinical translation. Well-designed prospective studies with standardized methodologies are needed to validate these biomarkers and clarify their role in routine diagnostic practice.