DNA methylation biomarkers in peripheral blood of patients with head and neck squamous cell carcinomas. A systematic review

Abstract

Background Head and neck squamous cell carcinomas (HNSCC) are often diagnosed in advanced stages. In search of new diagnostic tools, focus has shifted towards the biological properties of the HNSCC, and the number of different biomarkers under investigation is rapidly growing. Objectives The objective was to review the current literature regarding aberrantly methylated DNA found in peripheral blood plasma or serum in patients with HNSCC and to evaluate the diagnostic accuracy of these changes. Methods The inclusion criteria were clinical studies involving patients with verified HNSCC that reported findings of aberrantly methylated DNA in peripheral blood serum or plasma. We systematically searched PubMed, OVID Embase and Cochrane Library. In addition to the search, we performed forward and backward chaining in references and Web of Science. The protocol was registered in PROSPERO: CRD42019135406. Two authors independently extracted data. The quality and the risk of bias of the included studies were assessed by the QUADAS-2 tool. Results A total of 1,743 studies were found eligible for screening, while ultimately seven studies were included. All studies were found to have methodological weaknesses, mainly concerning patient selection bias. The best individual marker of HNSCC was Septin 9 in plasma with a sensitivity of 57% and a specificity of 95%. Conclusions None of the aberrantly methylated genes found in the retrieved studies are applicable as single diagnostic markers for HNSCC and the best gene-panels still lack diagnostic accuracy. Future studies may benefit from newer sequencing techniques but validation studies with well-designed cohorts are also needed in the process of developing epigenetic based diagnostic tests for HNSCC.

Plasma cell‐free DNA methylome profiling in pre‐ and post‐surgery oral cavity squamous cell carcinoma

“…HNSCC is a heterogenous disease and thus focusing on cfDNA DNAme may be advantageous to increase specificity. Previous studies have focused on targeted panels of methylation in either serum/plasma of HNSCC patients 22–28 . Recently, a study by Burgener et al 29 did demonstrate tumor‐naïve detection of ctDNA by simultaneously profiling mutations and methylation.…”

recountmethylationenables flexible analysis of public blood DNA methylation array data

“…We address these outstanding issues in this article using novel cross-study and cross-platform analyses, confining attention to normal human blood samples. Blood DNAm is often probed in epigenome-wide association studies (EWAS) to discover, test and validate biomarkers ( Li et al , 2012 ; Locke et al , 2019 ; Mikeska and Craig, 2014 ) for diseases, such as type II diabetes ( Bacos et al , 2016 ; Dayeh et al , 2016 ; Willmer et al , 2018 ), obesity ( Samblas et al , 2019 ), non-alcoholic fatty liver disease ( Hyun and Jung, 2020 ), asthma ( Thibeault and Laprise, 2019 ) and dementia ( Fransquet et al , 2020 ), as well as colorectal ( Alizadeh-Sedigh et al , 2021 ; Dong and Ren, 2018 ; Jensen et al , 2019 ; Lin et al , 2021 ), esophageal ( Yu et al , 2018 ), breast ( Guan et al , 2019 ), pancreatic ( Henriksen and Thorlacius-Ussing, 2021 ) and head-and-neck ( Danstrup et al , 2020 ) cancers. It is widely used to study biological aging ( Haftorn et al , 2021 ; Hannum et al , 2013 ; Horvath, 2013 ; Merid et al , 2020 ) and normal tissue epigenetics ( Åsenius et al , 2020 ; Huang et al , 2016 ), including development and function of the immune system ( Parveen and Dhawan, 2021 ).…”

recountmethylation enables flexible analysis of public blood DNA methylation array data

“…We address these outstanding issues in the present paper using novel cross-study and cross-platform analyses, confining attention to normal human blood samples. Blood DNAm is often probed in epigenome-wide association studies (EWAS) to discover, test, and validate biomarkers [8][9][10] for diseases such as type II diabetes [11][12][13], obesity [14], non-alcoholic fatty liver disease [15], asthma [16], and dementia [17], as well as colorectal [18][19][20][21], esophageal [22], breast [23], pancreatic [24], and head-and-neck [25] cancers. It is widely used to study biological aging [26][27][28][29] and normal tissue epigenetics [30,31], including development and function of the immune system [32].…”