Circulating cell-free nucleic acids as biomarkers in colorectal cancer screening and diagnosis - an update.
Béla MolnárOrsolya GalambAlexandra KalmárBarbara Kinga BartákZsófia Brigitta NagyKinga TóthZsolt TulassayPéter IgazMagdolna DankPublished in: Expert review of molecular diagnostics (2019)
Introduction: Screening methods for one of the most frequently diagnosed malignancy, colorectal cancer (CRC), have limitations. Circulating cell-free nucleic acids (cfNA) hold clinical relevance as screening, prognostic and therapy monitoring markers. Area covered: In this review, we summarize potential CRC-specific cfNA biomarkers, the recently developed sample preparation techniques, their applications, and pitfalls. Expert opinion: Automated extraction of cfDNA is highly reproducible, however, cfDNA yield is less compared to manual isolation. Quantitative and highly sensitive detection techniques (e.g. digital PCR, NGS) can be applied to analyze genetic and epigenetic changes. Detection of DNA mutations or methylation in cfDNA and related altered levels of mRNA, miRNA, and lncRNA may improve early cancer recognition, based on specific, CRC-related patterns. Detection of cfDNA mutations (e.g. TP53, KRAS, APC) has limited diagnostic sensitivity (40-60%), however, methylated DNA including SEPT9, SFRP1, SDC2 can be applied with higher sensitivity (up to 90%) for CRC. Circulating miRNAs (e.g. miR-21, miR-92, miR-141) provide comparably high sensitivity for CRC as the circulating tumor cell mRNA markers (e.g. EGFR, CK19, CK20, CEA). Automation of cfNA isolation coupled with quantitative analysis of CRC-related, highly sensitive biomarkers may enhance CRC screening and early detection in the future.
Keyphrases
- cell free
- circulating tumor
- long non coding rna
- sensitive detection
- cell proliferation
- long noncoding rna
- loop mediated isothermal amplification
- circulating tumor cells
- dna methylation
- small cell lung cancer
- genome wide
- colorectal cancer screening
- high resolution
- machine learning
- label free
- squamous cell carcinoma
- real time pcr
- protein kinase
- quantum dots
- single molecule
- papillary thyroid
- high throughput
- risk assessment
- bone marrow
- molecularly imprinted
- deep learning
- living cells
- cell therapy
- wild type
- drug induced