Finding new cancer epigenetic and genetic biomarkers from cell-free DNA by combining SALP-seq and machine learning: esophageal cancer as an example

Abstract

Background: Cancer is an important public health problem worldwide and its early diagnosis and effective prognosis are critical for its treatment. In recent years, as a good material for cancer liquid biopsy, plasma cell-free DNA (cfDNA) has been widely analyzed by next generation sequencing (NGS) for finding new molecular markers for cancer diagnosis such as size, methylation and end coordinate. However, the current studies did not still involve esophageal cancer (ESCA), a main cancer that seriously threatens human health and life in China. Here we therefore tried to find new biomarkers for this cancer from cfDNA. Materials & methods: Thirty cfDNA samples from 26 ESCA patients and 4 healthy people were used to construct the NGS libraries and sequenced by using SALP-seq. The sequencing data were analyzed with variant bioinformatics methods for finding ESCA molecular biomarkers. Results & conclusion: We identified 103 epigenetic markers (including 54 genome-wide and 49 promoter markers) and 37 genetic markers for ESCA. These markers provide new molecular biomarkers for ESCA diagnosis, prognosis and therapy. Importantly, this study provides a new pipeline for finding new molecular markers for cancers from cfDNA by combining SALP-seq and machine learning. Finally, by finding new molecular markers for ESCA from cfDNA, this study sheds important new insights on the clinical worth of cfDNA. 2 the incidence of cancer has not changed significantly before, cancer mortality has continued to decline, not only because of the development of medical standards, but also for preventive screening.Tissue biopsy is still the gold standard for diagnosing tumors, but due to the traumatic nature of patients, it brings a lot of interference to the dynamic treatment of patients. There are also many risks and ethical issues in tissue biopsy, which makes it have certain limitations. Liquid biopsy is a kind of cutting-edge technology to analyze a range of tumor material in the blood or other body fluids in a minimally invasive or noninvasive manner. The tumor material includes circulating tumor cells (CTCs), cell-free tumor DNA (ctDNA), messenger RNA (mRNA), microRNA (miRNA), and exosomes. Of these tumor biomarkers, ctDNA are most widely recognized in clinical application 4 . Comparing to ctDNA, cell-free DNA (cfDNA) is a broader term which describes DNA that is freely circulating, but is not necessarily of tumor origin. CtDNA refers to the cfDNA from tumor.CfDNA in human body fluids, such as plasma, was discovered in 1948 5 . Most of the plasma cfDNA originated from the hematopoietic system in healthy subjects, but in clinical patients (e.g. pregnancy and cancer), the related cells/tissues would release additional DNA into the plasma 6,7 . The detection of this perturbation would allow us to diagnose the abnormality for people in a noninvasive way. In recent years, methods based on the analysis of plasma cfDNA which is as an emerging technology have been largely explored for noninvasive prenatal testing (NIPT) and cancer liquid biopsy 8,9...

Computational challenges in detection of cancer using cell-free DNA methylation

“…One such liquid biopsy-derived method uses cancer traces obtained from cell-free DNA (cfDNA). These fragments are called circulating tumor DNA (ctDNA) and have shown the potential to help in the field of cancer diagnosis, and prognosis [2] .…”