Comprehensive circulating microRNA profile as a supersensitive biomarker for early-stage lung cancer screening

J Cancer Res Clin Oncol. 2023 Sep;149(11):8297-8305. doi: 10.1007/s00432-023-04728-9. Epub 2023 Apr 19.

Abstract

Purpose: Less-invasive early diagnosis of lung cancer is essential for improving patient survival rates. The purpose of this study is to demonstrate that serum comprehensive miRNA profile is high sensitive biomarker to early-stage lung cancer in direct comparison to the conventional blood biomarker using next-generation sequencing (NGS) technology combined with automated machine learning (AutoML).

Methods: We first evaluated the reproducibility of our measurement system using Pearson's correlation coefficients between samples derived from a single pooled RNA sample. To generate comprehensive miRNA profile, we performed NGS analysis of miRNAs in 262 serum samples. Among the discovery set (57 patients with lung cancer and 57 healthy controls), 1123 miRNA-based diagnostic models for lung cancer detection were constructed and screened using AutoML technology. The diagnostic faculty of the best performance model was evaluated by inspecting the validation samples (74 patients with lung cancer and 74 healthy controls).

Results: The Pearson's correlation coefficients between samples derived from the pooled RNA sample ≥ 0.98. In the validation analysis, the best model showed a high AUC score (0.98) and a high sensitivity for early stage lung cancer (85.7%, n = 28). Furthermore, in comparison to carcinoembryonic antigen (CEA), a conventional blood biomarker for adenocarcinoma, the miRNA-based model showed higher sensitivity for early-stage lung adenocarcinoma (CEA, 27.8%, n = 18; miRNA-based model, 77.8%, n = 18).

Conclusion: The miRNA-based diagnostic model showed a high sensitivity for lung cancer, including early-stage disease. Our study provides the experimental evidence that serum comprehensive miRNA profile can be a highly sensitive blood biomarker for early-stage lung cancer.

Keywords: Automated machine learning; Lung cancer; Next-generation sequencing; Serum; microRNA.

MeSH terms

  • Biomarkers, Tumor / genetics
  • Carcinoembryonic Antigen
  • Case-Control Studies
  • Circulating MicroRNA*
  • Early Detection of Cancer
  • Humans
  • Lung Neoplasms* / diagnosis
  • Lung Neoplasms* / genetics
  • MicroRNAs* / genetics
  • Reproducibility of Results

Substances

  • Circulating MicroRNA
  • Carcinoembryonic Antigen
  • Biomarkers, Tumor
  • MicroRNAs