BACKGROUND: Oropharyngeal squamous cell carcinomas (OpSCCs) are commonly associated with high rates of treatment failure. OBJECTIVES: To evaluate methylation-based markers in plasma from OpSCC patients as emerging tools for accurate/noninvasive follow-up. METHODS: Pretreatment formalin-fixed paraffin-embedded (FFPE) biopsies (n = 52) and paired plasma (n = 15) were tested for the methylation of CCNA1, DAPK, CDH8, and TIMP3 by droplet digital PCR (ddPCR). RESULTS: Seventy-one percent (37/52) of the biopsies showed methylation of at least one of the evaluated genes and tumor CCNA1 methylation was associated with recurrence-free survival. Methylated circulating tumor DNA (meth-ctDNA) was detected in 11/15 (73.3%) plasma samples; conversely, plasma samples from healthy controls were all negative for DNA methylation (area under the curve = 0.867; 95% confidence interval = 0.720-1.000). Additionally, preliminary results on the detection of meth-ctDNA in plasma collected during follow-up closely matched patient outcome. CONCLUSIONS: The results suggest the feasibility of detecting meth-ctDNA in plasma using ddPCR and a possible application on routine setting after further validation.
BACKGROUND: Oropharyngeal squamous cell carcinomas (OpSCCs) are commonly associated with high rates of treatment failure. OBJECTIVES: To evaluate methylation-based markers in plasma from OpSCC patients as emerging tools for accurate/noninvasive follow-up. METHODS: Pretreatment formalin-fixed paraffin-embedded (FFPE) biopsies (n = 52) and paired plasma (n = 15) were tested for the methylation of CCNA1, DAPK, CDH8, and TIMP3 by droplet digital PCR (ddPCR). RESULTS: Seventy-one percent (37/52) of the biopsies showed methylation of at least one of the evaluated genes and tumor CCNA1 methylation was associated with recurrence-free survival. Methylated circulating tumor DNA (meth-ctDNA) was detected in 11/15 (73.3%) plasma samples; conversely, plasma samples from healthy controls were all negative for DNA methylation (area under the curve = 0.867; 95% confidence interval = 0.720-1.000). Additionally, preliminary results on the detection of meth-ctDNA in plasma collected during follow-up closely matched patient outcome. CONCLUSIONS: The results suggest the feasibility of detecting meth-ctDNA in plasma using ddPCR and a possible application on routine setting after further validation.
Authors: Vasudha Mishra; Alka Singh; Xiangying Chen; Ari J Rosenberg; Alexander T Pearson; Alex Zhavoronkov; Peter A Savage; Mark W Lingen; Nishant Agrawal; Evgeny Izumchenko Journal: Br J Cancer Date: 2021-12-07 Impact factor: 7.640
Authors: Araceli Diez-Fraile; Joke De Ceulaer; Charlotte Derpoorter; Christophe Spaas; Tom De Backer; Philippe Lamoral; Johan Abeloos; Tim Lammens Journal: Int J Mol Sci Date: 2022-02-22 Impact factor: 5.923