Circulating Exosomal miRNAs as Biomarkers for the Diagnosis and Prognosis of Colorectal Cancer

Santos, Katiusse Alves dos; Santos, Ivanaldo; Silva, Carollyne Santos; Ribeiro, Hériks Gomes; Domingos, Igor de Farias; Silbiger, Vivian Nogueira

doi:10.3390/ijms22010346

Cited by 29 publications

(22 citation statements)

References 54 publications

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“…In total, more than 20 miRNA clusters have been correlated with CRC recurrence in small-scale studies involving less than 100 patients by means of RNA sequencing (RNA-Seq) and/or qRT-PCR. However, the gold standard miRNA detection method and the sensitivity and specificity profile of the technique are yet to be determined [ 127 ].…”

Section: Discussionmentioning

confidence: 99%

Resectable Colorectal Cancer: Current Perceptions on the Correlation of Recurrence Risk, Microbiota and Detection of Genetic Mutations in Liquid Biopsies

Koulouris

Tsagkaris

Messaritakis

et al. 2021

Cancers

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Metastatic colorectal cancer (mCRC) remains a highly lethal malignancy, although considerable progress has resulted from molecular alterations in guiding optimal use of available treatments. CRC recurrence remains a great barrier in the disease management. Hence, the spotlight turns to newly mapped fields concerning recurrence risk factors in patients with resectable CRC with a focus on genetic mutations, microbiota remodeling and liquid biopsies. There is an urgent need for novel biomarkers to address disease recurrence since specific genetic signatures can identify a higher or lower recurrence risk (RR) and, thus, be used both as biomarkers and treatment targets. To a large extent, CRC is mediated by the immune and inflammatory interplay of microbiota, through intestinal dysbiosis. Clarification of these mechanisms will yield new opportunities, leading not only to the appropriate stratification policies, but also to more precise, personalized monitoring and treatment navigation. Under this perspective, early detection of post-operative CRC recurrence is of utmost importance. Ongoing trials, focusing on circulating tumor cells (CTCs) and, even more, circulating tumor DNA (ctDNA), seem to pave the way to a promising, minimally invasive but accurate and life-saving monitoring, not only supporting personalized treatment but favoring patients’ quality of life, as well.

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Section: Discussionmentioning

confidence: 99%

Resectable Colorectal Cancer: Current Perceptions on the Correlation of Recurrence Risk, Microbiota and Detection of Genetic Mutations in Liquid Biopsies

Koulouris

Tsagkaris

Messaritakis

et al. 2021

Cancers

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“…Accordingly, there are several CEx-miRNAs related to specific CRC staging with a dual biomarker property whereby they can function as diagnosis and prognosis biomarkers (see Table 3 ). It is pivotal to mention that the best performance results for CRC diagnosis and prognosis are based on CEx-miRNAs panels (e.g., [ 137 , 138 ]), highlighting the importance of multitargeted-based detections to enhance early diagnoses and prognoses for CRC and other cancers.…”

Section: Cex-mirnas For Crc Diagnosismentioning

confidence: 99%

“…When 3p/5p were not mentioned, the annotation with higher reads was used when possible. A focused review on circulating exosomal miRNA and their role in the diagnosis, prognosis, surveillance, and monitoring of CRC can be found in [ 138 ].…”

Section: Figurementioning

confidence: 99%

CRISPR/Cas13-Based Platforms for a Potential Next-Generation Diagnosis of Colorectal Cancer through Exosomes Micro-RNA Detection: A Review

Durán-Vinet

Araya‐Castro

Calderón

et al. 2021

Cancers

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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.

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“…The miR-21 was reported to be highly expressed in various CRC cell exosomes, plasma exosomes and tissues, and correlated with disease staging, liver metastasis and prognosis, which could be used as a reference marker for gastrointestinal cancers ( 12 ). Nearly a hundred exosome miRNAs, such as miR-23a, miR-92a, miR-1246, and miR-486, have been identified as promising biomarkers for CRC ( 13 – 17 ). However, the correlation of exosome miRNAs with CRC staging and how it affects CRC progression is less understood.…”

Section: Introductionmentioning

confidence: 99%

Identification of stage-associated exosome miRNAs in colorectal cancer by improved robust and corroborative approach embedded miRNA-target network

Long

Tian²,

Chai³

et al. 2022

Front. Med.

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BackgroundColorectal cancer (CRC) is a common gastrointestinal tumor with high morbidity and mortality. At the molecular level, patients at different stages present considerable heterogeneity. Although the miRNA in exosome is an effective biomarker to reveal tumor progression, studies based on stage-associated exosome miRNA regulatory network analysis still lacking. This study aims to identify CRC stage-associated exosome miRNAs and reveal their potential function in tumor progression.MethodsIn this study, serum and cellular exosome miRNA expression microarrays associated with CRC were downloaded from GEO database. Stage-common (SC) and stage-specific (SS) differentially expressed miRNAs were extracted and their targets were identified based on 11 databases. Furthermore, miRNA SC and SS regulatory function networks were built based on the CRC phenotypic relevance of miRNA targets, and the corresponding transcription factors were identified. Concurrently, the potential stage-associated miRNAs were identified by receiver-operating characteristic (ROC) curve analysis, survival analysis, drug response analysis, ceRNA analysis, pathway analysis and a comprehensive investigation of 159 publications.ResultsTen candidate stage-associated miRNAs were identified, with three SC (miR-146a-5p, miR-22-3p, miR-23b-3p) and seven SS (I: miR-301a-3p, miR-548i; IIIA: miR-23a-3p; IV: miR-194-3p, miR-33a-3p, miR-485-3p, miR-194-5p) miRNAs. Additionally, their targets were enriched in several vital cancer-associated pathways such as TGF-beta, p53, and hippo signaling pathways. Moreover, five key hotspot target genes (CCNA2, MAPK1, PTPRD, MET, and CDKN1A) were demonstrated to associated with better overall survival in CRC patients. Finally, miR-23b-3p, miR-301a-3p and miR-194-3p were validated being the most stably expressed stage-associated miRNAs in CRC serum exosomes, cell exosomes and tissues.ConclusionsThese CRC stage-associated exosome miRNAs aid to further mechanism research of tumor progression and provide support for better clinical management in patients with different stages.

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Circulating Exosomal miRNAs as Biomarkers for the Diagnosis and Prognosis of Colorectal Cancer

Cited by 29 publications

References 54 publications

Resectable Colorectal Cancer: Current Perceptions on the Correlation of Recurrence Risk, Microbiota and Detection of Genetic Mutations in Liquid Biopsies

Resectable Colorectal Cancer: Current Perceptions on the Correlation of Recurrence Risk, Microbiota and Detection of Genetic Mutations in Liquid Biopsies

CRISPR/Cas13-Based Platforms for a Potential Next-Generation Diagnosis of Colorectal Cancer through Exosomes Micro-RNA Detection: A Review

Identification of stage-associated exosome miRNAs in colorectal cancer by improved robust and corroborative approach embedded miRNA-target network

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