The rational application of liquid biopsy based on next-generation sequencing in advanced non-small cell lung cancer

Cancer Med. 2023 Mar;12(5):5603-5614. doi: 10.1002/cam4.5410. Epub 2022 Nov 7.

Abstract

Background: Plasma and tissue biopsy have both used for targeting actionable driver gene mutations in lung cancer, whose concordance is imperfect. A reliable method to predict the concordance is urgently needed to ease clinical application.

Methods: A total of 1012 plasma samples, including 519 with paired-tissue biopsy samples, derived from lung adenocarcinoma patients were retrospectively enrolled. We assessed the associations of several clinicopathological characteristics and serum tumor markers with the concordance between plasma and tissue biopsies.

Results: When carcinoembryonic antigen (CEA) levels were higher than thresholds of 15.01 ng/ml and 51.15 ng/ml, the positive predictive value of concordance reached 90% and 95%, respectively. When CEA levels were lower than thresholds of 5.19 ng/ml and 3.26 ng/mL, the negative predictive value of concordance reached 45% and 50%. The performance of CYFRA21-1 in predicting concordance was similar but inferior to CEA (AUC: 0.727 vs. 0.741, p = 0.633). The performance of CEA combined with CYFRA21-1 in predicting the concordance was similar to that of the combination of independent factors derived from the LASSO regression model (AUC: 0.796 vs. 0.818, p = 0.067). CEA (r = 0.47, p < 0.01) and CYFRA21-1 levels (r = 0.45, p < 0.05) were significantly correlated with the maximum variant allele frequency, respectively.

Conclusions: CEA combined with CYFRA21-1 could effectively predict the concordance between plasma and tissue biopsies, which could be used for evaluating the priority of plasma and tissue biopsies for gene testing to timely guide clinical applications in advanced lung adenocarcinoma patients.

Keywords: circulating tumor DNA; liquid biopsy; next generation sequencing; non-small cell lung cancer; serum tumor marker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung* / genetics
  • Antigens, Neoplasm
  • Biomarkers, Tumor / genetics
  • Carcinoembryonic Antigen
  • Carcinoma, Non-Small-Cell Lung* / diagnosis
  • Carcinoma, Non-Small-Cell Lung* / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Keratin-19
  • Liquid Biopsy
  • Lung Neoplasms* / diagnosis
  • Lung Neoplasms* / genetics
  • Retrospective Studies

Substances

  • antigen CYFRA21.1
  • Carcinoembryonic Antigen
  • Antigens, Neoplasm
  • Keratin-19
  • Biomarkers, Tumor