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اولین کنگره بین المللی رویکردهای نوین سبک زندگی، پیشگیری و درمان سرطان
Liquid Biopsy Of Circulating Cell-Free DNA For Cancer Early Detection
نویسندگان :
Hedyeh Anbiaie (دانشگاه آزاد اسلامی واحد مشهد) , Fatemeh Abiat (دانشگاه آزاد اسلامی واحد مشهد) , Fatemeh Aboutorabzadeh (دانشگاه آزاد اسلامی واحد مشهد)
کلمات کلیدی :
Cancer،cfDNA،Liquid Biopsy
چکیده :
Background: Effective screening modalities are currently available for only a small subset of cancers, and they generally have suboptimal performance with complicated procedures. Therefore, there is an urgent need to develop simple, accurate, and non-invasive methods for early detection of cancers. As a noninvasive approach, liquid biopsy has great potential to be the biomarkers for the early detection, recurrence monitoring, and prognosis of cancer. Circulating tumor DNA (ctDNA) is a promising biomarker that carries cancer-specific genetic and epigenetic aberrations, which therefore can be used as a surrogate source of tumor DNA in cancer diagnosis and prognosis prediction. Methods: This study was a review study that conducted by using PubMed and Science Direct databases by using keywords of Cancer; cfDNA. Finally 14 out of 9688 results up to 2023 were examined in detail. Results: Liquid biopsy is capable of detecting cancers through detecting circulating tumor cells, exosomes, proteins, or metabolites, mRNA, microRNAs (miRNAs), cfDNA, etc. Mutation, methylation, and fragment patterns are the main sequenced biomarkers of cfDNA for the early detection of cancers. Whole-genome sequencing (WGS) has revealed that tumor-derived cfDNA (circulating tumor DNA [ctDNA]) is in general shorter than non-tumor DNA. The clinical test performance of blood-based ctDNAs as a diagnostic tool has shown 75% sensitivity and 89% specificity, indicating blood-based ctDNA analysis of cancer mutations is a specific, minimally invasive test for the diagnosis of cancer. The detection of tumor-derived cell-free DNA in plasma is one of the most promising directions in cancer diagnosis. The major challenge in such an approach is how to identify the tiny amount of tumor DNAs out of total cell-free DNAs in blood. An ultrasensitive cancer detection method is proposed, termed ‘CancerDetector’, using the DNA methylation profiles of cell-free DNAs. The key of this method is to probabilistically model the joint methylation states of multiple adjacent CpG sites on an individual sequencing read, in order to exploit the pervasive nature of DNA methylation for signal amplification. Therefore, CancerDetector can sensitively identify a trace amount of tumor cfDNAs in plasma, at the level of individual reads. 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. Among genomic and epigenomic alterations, the methylation of CpG sites provides not only tissue-specific information, but also cancer-specific information, making it a promising approach for early detection of multi-cancers. Conclusions: Clinical applications of liquid biopsy for early cancer detection still remains a substantial challenge. Even a minor lack in assay specificity would lead to numerous false-positive results, causing avoidable concern of patients and enormous subsequent diagnosis costs, while false-negative results would retard important therapeutic interventions. Although numerous studies have demonstrated the potential of ctDNA as biomarkers for early detection and diagnosis of cancer, there still remain some crucial challenges that need to be addressed. For early-stage cancer, very little ctDNA is present and the genomic profiles in the original tumor are unknown, so the detection assays should be extremely sensitive.
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