Abstract
Simple SummaryColorectal cancer is one of the most prevalent cancers, whereas a significant number of cases are diagnosed in late cancer stages, and survival rates drop dramatically. Micro-RNAs (miRNAs) from cancer-derived exosomes have shown promising diagnosis potential. Our review aims to present CRISPR/Cas-based molecular platforms as an inexpensive, swift, and robust detection tool of cancer-derived exosome micro-RNAs to streamline future applications based on the novel CRISPR/Cas-based platforms to achieve early CRC diagnosis.Colorectal cancer (CRC) is the third most prevalent cancer with the second highest mortality rate worldwide. CRC is a heterogenous disease with multiple risk factors associated, including obesity, smoking, and use of alcohol. Of total CRC cases, 60% are diagnosed in late stages, where survival can drop to about 10%. CRC screening programs are based primarily on colonoscopy, yet this approach is invasive and has low patient adherence. Therefore, there is a strong incentive for developing molecular-based methods that are minimally invasive and have higher patient adherence. Recent reports have highlighted the importance of extracellular vesicles (EVs), specifically exosomes, as intercellular communication vehicles with a broad cargo, including micro-RNAs (miRNAs). These have been syndicated as robust candidates for diagnosis, primarily for their known activities in cancer cells, including immunoevasion, tumor progression, and angiogenesis, whereas miRNAs are dysregulated by cancer cells and delivered by cancer-derived exosomes (CEx). Quantitative polymerase chain reaction (qPCR) has shown good results detecting specific cancer-derived exosome micro-RNAs (CEx-miRNAs) associated with CRC, but qPCR also has several challenges, including portability and sensitivity/specificity issues regarding experiment design and sample quality. CRISPR/Cas-based platforms have been presented as cost-effective, ultrasensitive, specific, and robust clinical detection tools in the presence of potential inhibitors and capable of delivering quantitative and qualitative real-time data for enhanced decision-making to healthcare teams. Thereby, CRISPR/Cas13-based technologies have become a potential strategy for early CRC diagnosis detecting CEx-miRNAs. Moreover, CRISPR/Cas13-based platforms’ ease of use, scalability, and portability also showcase them as a potential point-of-care (POC) technology for CRC early diagnosis. This study presents two potential CRISPR/Cas13-based methodologies with a proposed panel consisting of four CEx-miRNAs, including miR-126, miR-1290, miR-23a, and miR-940, to streamline novel applications which may deliver a potential early diagnosis and prognosis of CRC.
Highlights
Colorectal cancer (CRC) has gained significant relevance during the last five years due to its increasing incidence and mortality
This review presents the potential of CRISPR/Cas-based platforms that represent a significant opportunity for next-generation, early point-of-care (POC) detection of CRC via detecting its cancer-derived exosomes (CEx)-miRNAs
To halt its advance and provide quality healthcare, there is a need to strengthen and reinforce current traditional medical surveillance programs mainly based on invasive methods such as colonoscopies or molecular methods primarily based on RT-Quantitative polymerase chain reaction (qPCR), where both have challenges and limitations
Summary
Colorectal cancer (CRC) has gained significant relevance during the last five years due to its increasing incidence and mortality. This review presents the potential of CRISPR/Cas-based platforms that represent a significant opportunity for next-generation, early point-of-care (POC) detection of CRC via detecting its CEx-miRNAs. To achieve this, we briefly summarize CRC relevance, current CRC diagnosis tools, their challenges, and current clinical CRC biomarkers. CRC staging is based on three criteria: (1) cancer level of expansion in the intestine wall, (2) affection of other nearby structures, and (3) lymph nodes or distant organs being reached. These are described by the American Joint Committee on Cancer (AJCC) [41]. Thereby, molecular diagnosis has risen as a swift and affordable route to obtain an early CRC diagnosis [53], to be followed by suitable treatments, including chemotherapy [54], radiotherapy [55], immunotherapy [56], targeted therapy [57], and other therapies (further reading can be found in [9,58,59]), preventing, to some extent, patients’ deaths and life-quality deterioration
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