Circulating cell-free DNA sequencing for early detection of lung cancer

ABSTRACT

Introduction

Lung cancer is a leading cause of death in patients with cancer. Early diagnosis is crucial to improve the prognosis of patients with lung cancer. Plasma circulating cell-free DNA (cfDNA) contains comprehensive genetic and epigenetic information from tissues throughout the body, suggesting that early detection of lung cancer can be done non-invasively, conveniently, and cost-effectively using high-sensitivity techniques such as sequencing.

Areas covered

In this review, we summarize the latest technological innovations, coupled with next-generation sequencing (NGS), regarding genomic alterations, methylation, and fragmentomic features of cfDNA for the early detection of lung cancer, as well as their clinical advances. Additionally, we discuss the suitability of study designs for diagnostic accuracy evaluation for different target populations and clinical questions.

Expert opinion

Currently, cfDNA-based early screening and diagnosis of lung cancer faces many challenges, such as unsatisfactory performance, lack of quality control standards, and poor repeatability. However, the progress of several large prospective studies employing epigenetic features has shown promising predictive performance, which has inspired cfDNA sequencing for future clinical applications. Furthermore, the development of multi-omics markers for lung cancer, including genome-wide methylation and fragmentomics, is expected to play an increasingly important role in the future.

KEYWORDS:

• Circulating cell-free DNA
• fragmentomics
• lung cancer
• methylation
• screening and diagnosis

Article highlights

• Early diagnosis is crucial to improve the prognosis of patients with lung cancer. However, early diagnosis using conventional approaches is hampered by low accuracy and invasive procedures.

• Liquid biopsy is a promising direction, and current clinical advances regarding the genomic alteration, methylation, and fragmentomic features of cfDNA for the early detection of lung cancer are summarized.

• A framework of study design for evaluating the diagnostic accuracy of lung cancer biomarker development was proposed to answer different clinical questions.

• Challenges and opportunities for the early detection of lung cancer based on cfDNA are explored, and emerging technologies with early detection potential are introduced.

Acknowledgments

We would like to thank Dr. Linlin Yan for expression check-up and Editage (www.editage.cn) for English language editing.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Declaration of interest

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Author contribution statement

Jie Zhao and Yu Qi conceived of the work; Ruyue Xue and Lu Yang drafted the article; Meijia Yang and Fangfang Xue collected the data; Lifeng Li and Manjiao Liu analyzed data and prepared the tables and figures; Yong Ren revised the article.

Availability of supporting data

All data needed to evaluate the conclusions in the paper are presented in the paper.

Additional information

Funding

This manuscript was funded by grants from the Collaborative Innovation Major Project of Zhengzhou (Grant No. 20XTZX08017); The National Natural Science Foundation of China (Grant No. 82002433, 82203028)