MicroRNAs (miRNAs): Novel potential therapeutic targets in colorectal cancer

Ying, Yang; Meng, Wenjian; Wang, Ziqiang

doi:10.3389/fonc.2022.1054846

Cited by 9 publications

(3 citation statements)

References 129 publications

(120 reference statements)

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“…Furthermore, we identified the common exosomal and tissue miRNAs for CRC, which could be considered predictive biomarkers for mCRC [ 7 , 40 ]. Additionally, we focused on the CRC circulating miRNAs associated with tumor progression and also with treatment prediction [ 41 , 42 , 43 ]. Our analysis revealed five miRNAs, miR-92a-3p, miR-146a-5p, miR-221-3p, miR-484, miR-486-5p, and miR-143-3p, as suitable to be investigated for treatment predictions for mCRC.…”

Section: Methodsmentioning

confidence: 99%

Baseline Expression of Exosomal miR-92a-3p and miR-221-3p Could Predict the Response to First-Line Chemotherapy and Survival in Metastatic Colorectal Cancer

Gherman

Bălăcescu

Popa

et al. 2023

IJMS

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The status of predictive biomarkers in metastatic colorectal cancer is currently underdeveloped. Our study aimed to investigate the predictive value of six circulating exosomal miRNAs derived from plasma (miR-92a-3p, miR-143-3p, miR-146a-5p, miR-221-3p, miR-484, and miR-486-5p) for chemosensitivity, resistance patterns, and survival. Thirty-one metastatic colorectal cancer patients were selected before receiving first-line irinotecan- or oxaliplatin-based chemotherapy. Blood samples were harvested at baseline and 4–6 months after the initiation of chemotherapy. The levels of exosomal expression for each miRNA were analyzed by qPCR. Our results for patients receiving first-line FOLFOX showed significantly higher baseline levels of miR-92a-3p (p = 0.007 **), miR-146a-5p (p = 0.036 *), miR-221-3p (p = 0.047 *), and miR-484 (p = 0.009 **) in non-responders (NR) vs. responders (R). Of these, miR-92a-3p (AUC = 0.735), miR-221-3p (AUC = 0.774), and miR-484 (AUC = 0.725) demonstrated a predictive ability to discriminate responses from non-responses, regardless of the therapy used. Moreover, Cox regression analysis indicated that higher expression levels of miR-92a-3p (p = 0.008 **), miR-143-3p (p = 0.009 **), miR-221-3p (p = 0.016 *), and miR-486-5p (p = 0.019 *) at baseline were associated with worse overall survival, while patients expressing higher baseline miR-92a-3p (p = 0.003 **) and miR-486-5p (p = 0.003 **) had lower rates of progression-free survival. No predictive values for candidate microRNAs were found for the post-chemotherapy period. In line with these findings, we conclude that the increased baseline exosomal expression of miR-92a-3p and miR-221-3p seems to predict a lack of response to chemotherapy and lower OS. However, further prospective studies on more patients are needed before drawing practice-changing conclusions.

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Section: Methodsmentioning

confidence: 99%

Baseline Expression of Exosomal miR-92a-3p and miR-221-3p Could Predict the Response to First-Line Chemotherapy and Survival in Metastatic Colorectal Cancer

Gherman

Bălăcescu

Popa

et al. 2023

IJMS

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“…Overall, comprehending the involvement of DPYD and its interplay with miRNAs promises valuable insights for advancing targeted therapeutic modalities in rectal neoplasms management. (56),(62),(63)…”

Section: Introductionmentioning

confidence: 99%

“…Overall, MSH2 emerges as a promising target for rectal neoplasms, holding potential for therapeutic intervention. (54), (55),(56),(57)…”

Section: Introductionmentioning

confidence: 99%

AI-Enhanced RAIN Protocol: A Systematic Approach to Optimize Drug Combinations for Rectal Neoplasm Treatment

Dashti,

Kiaei,

Boush

et al. 2024

Preprint

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BackgroundRectal cancers, or rectal neoplasms, are tumors that develop from the lining of the rectum, the concluding part of the large intestine ending at the anus. These tumors often start as benign polyps and may evolve into malignancies over several years. The causes of rectal cancer are diverse, with genetic mutations being a key factor. These mutations lead to uncontrolled cell growth, resulting in tumors that can spread and damage healthy tissue. Age, genetic predisposition, diet, and hereditary conditions are among the risk factors. Treating rectal cancer is critical to prevent severe health issues and death. Untreated, it can cause intestinal blockage, metastasis, and deteriorate the patient’s quality of life. Effective treatment hinges on finding the right drug combinations to improve therapeutic outcomes. Given the intricacies of cancer biology, treatments often combine surgery, chemotherapy, and radiation, with drugs chosen to target different tumor growth mechanisms, aiming to reduce the tumor and limit side effects. The continuous advancement in cancer treatments highlights the need for ongoing research to discover new drug combinations, offering patients improved recovery prospects and a better quality of life. This background encapsulates a detailed yet succinct understanding of rectal neoplasms, their origins, the urgency of treatment, and the quest for effective drug therapies, paving the way for discussions on treatment advancements and patient care impacts.MethodThis study employed the RAIN protocol, comprising three steps: firstly, utilizing the GraphSAGE model to propose drug combinations for rectal neoplasm treatment Each node in the graph model is a drug or a human gene/protein that acts as potential target for the disease, and the edges are P-values between them; secondly, conducting a systematic review across various databases including Web of Science, Google Scholar, Scopus, Science Direct, PubMed, and Embase, with NLP investigation; and thirdly, employing a meta-analysis network to assess the efficacy of drugs and genes in relation to each other. All implementations was conducted using Python software.ResultThe study evaluated the efficacy of Oxaliplatin, Leucovorin, and Capecitabine in treating Rectal Neoplasms, confirming their effectiveness through a review of 30 studies. The p-values for individual drugs were 0.019, 0.019, and 0.016 respectively, while the combined use of all three yielded a p-value of 0.016.ConclusionGiven the significance of rectal neoplasms, policymakers are urged to prioritize the healthcare needs of affected individuals. Utilizing artificial intelligence within the RAIN protocol can offer valuable insights for tailoring effective drug combinations to better address the treatment and management of rectal neoplasms patients.Abstract FigureHighlightsRectal cancers, evolving from benign polyps to malignancies, underscore the critical need for timely and effective treatment to prevent severe health complications.Genetic mutations, a pivotal factor in rectal cancer, trigger uncontrolled cell growth and necessitate targeted drug therapies to combat tumor spread.The RAIN protocol, leveraging the GraphSAGE model and systematic reviews, offers a novel approach to identify potent drug combinations for rectal neoplasm treatment.The study’s findings advocate for policy intervention to ensure that healthcare systems adequately support individuals battling rectal neoplasms, with AI-driven protocols enhancing patient care.

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