Liquid biopsies based on DNA methylation as biomarkers for the detection and prognosis of lung cancer

Abstract

Lung cancer (LC) is the main cause of cancer-related mortality. Most LC patients are diagnosed in an advanced stage when the symptoms are obvious, and the prognosis is quite poor. Although low-dose computed tomography (LDCT) is a routine clinical examination for early detection of LC, the false-positive rate is over 90%. As one of the intensely studied epigenetic modifications, DNA methylation plays a key role in various diseases, including cancer and other diseases. Hypermethylation in tumor suppressor genes or hypomethylation in oncogenes is an important event in tumorigenesis. Remarkably, DNA methylation usually occurs in the very early stage of malignant tumors. Thus, DNA methylation analysis may provide some useful information about the early detection of LC. In recent years, liquid biopsy has developed rapidly. Liquid biopsy can detect and monitor both primary and metastatic malignant tumors and can reflect tumor heterogeneity. Moreover, it is a minimally invasive procedure, and it causes less pain for patients. This review summarized various liquid biopsies based on DNA methylation for LC. At first, we briefly discussed some emerging technologies for DNA methylation analysis. Subsequently, we outlined cell-free DNA (cfDNA), sputum, bronchoalveolar lavage fluid, bronchial aspirates, and bronchial washings DNA methylation-based liquid biopsy for the early detection of LC. Finally, the prognostic value of DNA methylation in cfDNA and sputum and the diagnostic value of other DNA methylation-based liquid biopsies for LC were also analyzed.

The Biological Characteristics and Differential Expression Patterns of TSSK1B Gene in Yak and Its Infertile Hybrid Offspring

“…A study on the promoter region of yak HIF found that demethylation may be related to the higher expression of HIF in yak tissues than in general cattle [39]. Abnormal DNA methylation has always served as the biomarker of many diseases [40][41][42], such as cancers [43]. As for the genome, the upstream 2000 bp from the transcription start site is generally considered as the promoter region of the gene [25].…”

Sequence-Based Platforms for Discovering Biomarkers in Liquid Biopsy of Non-Small-Cell Lung Cancer

“…Sputum samples have proven to be highly effective in detecting lung cancer progression early [ 143 , 144 ], specifically in active and former smokers. While relatively few studies have investigated DNAm changes occurring in lung cancer using urine, saliva and pleural effusion, they have still demonstrated the utility of using these liquid biopsy samples for early detection, as well as their success in separating lung cancer subtypes [ 145 ]. The majority of DNAm studies use bulk tissue; however, the methylomes of individual cell types differ, as demonstrated by cell-specific gene expression profiles [ 146 ].…”

Liquid Biopsy in Lung Cancer: Biomarkers for the Management of Recurrence and Metastasis

“…These profiles show remarkable differences even in early cancer stages, with certain methylation markers specific to particular cancers, whereas some are detectable pan-cancer [139,140]. Some markers have notable specificity to lung cancer metastasis [141]; however, the detection of these metastasis markers, and furthermore of recurrence, is a relatively novel and ongoing area of research [141][142][143].…”