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Nor WMFSBWM, Kwong SC, Fuzi AAM, Said NABM, Jamil AHA, Lee YY, Lee SC, Lim YAL, Chung I. Linking microRNA to metabolic reprogramming and gut microbiota in the pathogenesis of colorectal cancer (Review). Int J Mol Med 2025; 55:46. [PMID: 39820715 PMCID: PMC11759585 DOI: 10.3892/ijmm.2025.5487] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2024] [Accepted: 12/03/2024] [Indexed: 01/19/2025] Open
Abstract
Colorectal cancer (CRC), an emerging public health concern, is one of the leading causes of cancer morbidity and mortality worldwide. An increasing body of evidence shows that dysfunction in metabolic reprogramming is a crucial characteristic of CRC progression. Specifically, metabolic reprogramming abnormalities in glucose, glutamine and lipid metabolism provide the tumour with energy and nutrients to support its rapid cell proliferation and survival. More recently, microRNAs (miRNAs) appear to be involved in the pathogenesis of CRC, including regulatory roles in energy metabolism. In addition, it has been revealed that dysbiosis in CRC might play a key role in impairing the host metabolic reprogramming processes, and while the exact interactions remain unclear, the link may lie with miRNAs. Hence, the aims of the current review include first, to delineate the metabolic reprogramming abnormalities in CRC; second, to explain how miRNAs mediate the aberrant regulations of CRC metabolic pathways; third, linking miRNAs with metabolic abnormalities and dysbiosis in CRC and finally, to discuss the roles of miRNAs as potential biomarkers.
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Affiliation(s)
| | - Soke Chee Kwong
- Centre for Population Health (CePH), Department of Social and Preventive Medicine, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Afiqah Alyaa Md Fuzi
- Office of Deputy Vice Chancellor (Research and Innovation), Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Nur Akmarina Binti Mohd Said
- Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Amira Hajirah Abd Jamil
- Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, 16150 Kota Bharu, Malaysia
| | - Soo Ching Lee
- Department of Parasitology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Yvonne Ai-Lian Lim
- Department of Parasitology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
| | - Ivy Chung
- Department of Pharmacology, Faculty of Medicine, Universiti Malaya, 50603 Kuala Lumpur, Malaysia
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Kyrgiafini MA, Katsigianni M, Giannoulis T, Sarafidou T, Chatziparasidou A, Mamuris Z. Integrative Analysis of Whole-Genome and Transcriptomic Data Reveals Novel Variants in Differentially Expressed Long Noncoding RNAs Associated with Asthenozoospermia. Noncoding RNA 2025; 11:4. [PMID: 39846682 PMCID: PMC11755663 DOI: 10.3390/ncrna11010004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2024] [Revised: 01/05/2025] [Accepted: 01/08/2025] [Indexed: 01/24/2025] Open
Abstract
Background/Objectives: Asthenozoospermia, characterized by reduced sperm motility, is a common cause of male infertility. Emerging evidence suggests that noncoding RNAs, particularly long noncoding RNAs (lncRNAs), play a critical role in the regulation of spermatogenesis and sperm function. Coding regions have a well-characterized role and established predictive value in asthenozoospermia. However, this study was designed to complement previous findings and provide a more holistic understanding of asthenozoospermia, this time focusing on noncoding regions. This study aimed to identify and prioritize variants in differentially expressed (DE) lncRNAs found exclusively in asthenozoospermic men, focusing on their impact on lncRNA structure and lncRNA-miRNA-mRNA interactions. Methods: Whole-genome sequencing (WGS) was performed on samples from asthenozoospermic and normozoospermic men. Additionally, an RNA-seq dataset from normozoospermic and asthenozoospermic individuals was analyzed to identify DE lncRNAs. Bioinformatics analyses were conducted to map unique variants on DE lncRNAs, followed by prioritization based on predicted functional impact. The structural impact of the variants and their effects on lncRNA-miRNA interactions were assessed using computational tools. Gene ontology (GO) and KEGG pathway analyses were employed to investigate the affected biological processes and pathways. Results: We identified 4173 unique variants mapped to 258 DE lncRNAs. After prioritization, 5 unique variants in 5 lncRNAs were found to affect lncRNA structure, while 20 variants in 17 lncRNAs were predicted to disrupt miRNA-lncRNA interactions. Enriched pathways included Wnt signaling, phosphatase binding, and cell proliferation, all previously implicated in reproductive health. Conclusions: This study identifies specific variants in DE lncRNAs that may play a role in asthenozoospermia. Given the limited research utilizing WGS to explore the role of noncoding RNAs in male infertility, our findings provide valuable insights and a foundation for future studies.
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Affiliation(s)
- Maria-Anna Kyrgiafini
- Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, 41500 Larissa, Greece
| | - Maria Katsigianni
- Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, 41500 Larissa, Greece
| | - Themistoklis Giannoulis
- Laboratory of Biology, Genetics and Bioinformatics, Department of Animal Sciences, University of Thessaly, Gaiopolis, 41336 Larissa, Greece
| | - Theologia Sarafidou
- Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, 41500 Larissa, Greece
| | - Alexia Chatziparasidou
- Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, 41500 Larissa, Greece
- Embryolab IVF Unit, St. 173-175 Ethnikis Antistaseos, Kalamaria, 55134 Thessaloniki, Greece
| | - Zissis Mamuris
- Laboratory of Genetics, Comparative and Evolutionary Biology, Department of Biochemistry and Biotechnology, University of Thessaly, Viopolis, Mezourlo, 41500 Larissa, Greece
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Yi C, Lu L, Li Z, Guo Q, Ou L, Wang R, Tian X. Plant-derived exosome-like nanoparticles for microRNA delivery in cancer treatment. Drug Deliv Transl Res 2025; 15:84-101. [PMID: 38758499 DOI: 10.1007/s13346-024-01621-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/05/2024] [Indexed: 05/18/2024]
Abstract
Plant-derived exosome-like nanoparticles (PELNs) are natural nanocarriers and effective delivery systems for plant microRNAs (miRNAs). These PELN-carrying plant miRNAs can regulate mammalian genes across species, thereby increasing the diversity of miRNAs in mammals and exerting multi-target effects that play a crucial role in diseases, particularly cancer. PELNs demonstrate exceptional stability, biocompatibility, and targeting capabilities that protect and facilitate the up-take and cross-kingdom communication of plant miRNAs in mammals. Primarily ingested and absorbed within the gastrointestinal tract of mammals, PELNs preferentially act on the intestine to regulate intestinal homeostasis through functional miRNA activity. The oncogenesis and progression of cancer are closely associated with disruptions in intestinal barriers, ecological imbalances, as well as secondary changes, such as abnormal inflammatory reactions caused by them. Therefore, it is imperative to investigate whether PELNs exert their anticancer effects by regulating mammalian intestinal homeostasis and inflammation. This review aims to elucidate the intrinsic crosstalk relationships and mechanisms of PELNs-mediated miRNAs in maintaining intestinal homeostasis, regulating inflammation and cancer treatment. Furthermore, serving as exceptional drug delivery systems for miRNAs molecules, PELNs offer broad prospects for future applications, including new drug research and development along with drug carrier selection within targeted drug delivery approaches for cancer therapy.
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Affiliation(s)
- Chun Yi
- Department of Pathology, Faculty of Medicine, Hunan University of Chinese Medicine, 410208, Changsha, Hunan, China
| | - Linzhu Lu
- College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, 300 Xueshi Road, Yuelu District, 410208, Changsha, Hunan Province, China
| | - Zhaosheng Li
- College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, 300 Xueshi Road, Yuelu District, 410208, Changsha, Hunan Province, China
| | - Qianqian Guo
- College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, 300 Xueshi Road, Yuelu District, 410208, Changsha, Hunan Province, China
| | - Longyun Ou
- The First Hospital of Hunan University of Chinese Medicine, 410208, Changsha, Hunan, China
| | - Ruoyu Wang
- Department of Infectious Diseases, Department of Liver Diseases, The First Hospital of Hunan University of Chinese Medicine, 95 Shaoshan Rd, Hunan, 410208, Changsha, China.
| | - Xuefei Tian
- College of Integrated Chinese and Western Medicine, Hunan University of Chinese Medicine, 300 Xueshi Road, Yuelu District, 410208, Changsha, Hunan Province, China.
- Hunan Province University Key Laboratory of Oncology of Tradional Chinese Medicine, 410208, Changsha, Hunan, China.
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Douvris A, Viñas JL, Akbari S, Tailor K, Lalu MM, Burger D, Burns KD. Systematic review of microRNAs in human acute kidney injury. Ren Fail 2024; 46:2419960. [PMID: 39477814 PMCID: PMC11533245 DOI: 10.1080/0886022x.2024.2419960] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 09/25/2024] [Accepted: 10/17/2024] [Indexed: 11/06/2024] Open
Abstract
INTRODUCTION Early diagnosis of acute kidney injury (AKI) is limited with current tools. MicroRNAs (miRNAs) are implicated in AKI pathogenesis in preclinical models, but less is known about their role in humans. We conducted a systematic review to identify dysregulated miRNAs in humans with AKI. METHODS We searched Ovid MEDLINE, Embase, Web of Science, and CENTRAL (August 21, 2023) for studies of human subjects with AKI. We excluded reviews and pre-clinical studies without human data. The primary outcome was dysregulated miRNAs in AKI. Two reviewers screened abstracts, reviewed full texts, performed data extraction and quality assessment (Newcastle Ottawa Scale). RESULTS We screened 2,456 reports and included 92 for synthesis without meta-analysis. All studies except one were observational. Studies were grouped by etiology of AKI: cardiac surgery-associated (CS-AKI, n = 13 studies), sepsis (n = 25), nephrotoxic (n = 9), kidney transplant (n = 26), and other causes (n = 19). In total, 128 miRNAs were identified to be dysregulated across AKI studies (45 miRNAs upregulated, 55 downregulated, 28 both). miR-21 was the most frequently reported (n = 17 studies) and it was increased in all etiologies except CS-AKI where it was decreased (n = 3 studies). Study limitations included bias due to targeted approaches, absence of clinical data/controls, and miRNA normalization methods. Overall study quality was fair (median 5/9, range 2-8 points). CONCLUSION Dysregulated miRNAs, particularly miR-21, have potential as AKI biomarkers. These results should be interpreted cautiously due to methodological limitations. Standardized methods and unbiased approaches are needed to validate candidate miRNA biomarkers.Registration: International Prospective Register of Systematic Reviews (PROSPERO CRD42020201253).
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Affiliation(s)
- Adrianna Douvris
- Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada
- Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Jose L. Viñas
- Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada
| | - Shareef Akbari
- Division of Nephrology, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Karishma Tailor
- Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada
| | - Manoj M. Lalu
- Department of Anesthesiology and Pain Medicine, Clinical Epidemiology and Regenerative Medicine Program, Blueprint Translational Research Group, The Ottawa Hospital Research Institute, The University of Ottawa and The Ottawa Hospital, Ottawa, Ontario, Canada
| | - Dylan Burger
- Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada
- Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada
| | - Kevin D. Burns
- Division of Nephrology, Department of Medicine and Kidney Research Centre, Ottawa Hospital Research Institute, University of Ottawa, Ontario, Canada
- Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada
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Mannucci A, Goel A. Stool and blood biomarkers for colorectal cancer management: an update on screening and disease monitoring. Mol Cancer 2024; 23:259. [PMID: 39558327 PMCID: PMC11575410 DOI: 10.1186/s12943-024-02174-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2024] [Accepted: 11/07/2024] [Indexed: 11/20/2024] Open
Abstract
BACKGROUND Biomarkers have revolutionized the management of colorectal cancer (CRC), facilitating early detection, prevention, personalized treatment, and minimal residual disease (MRD) monitoring. This review explores current CRC screening strategies and emerging biomarker applications. MAIN BODY We summarize the landscape of non-invasive CRC screening and MRD detection strategies, discuss the limitations of the current approaches, and highlight the promising potential of novel biomarker solutions. The fecal immunochemical test remained the cornerstone of CRC screening, but its sensitivity has been improved by assays that combined its performance with other stool analytes. However, their sensitivity for advanced adenomas and the patient compliance both remain suboptimal. Blood-based tests promise to increase compliance but require further refinement to compete with stool-based biomarker tests. The ideal scenario involves leveraging blood tests to increase screening participation, and simultaneously promote stool- and endoscopy-based screening among those who are compliant. Once solely reliant on upfront surgery followed by stage and pathology-driven adjuvant chemotherapy, the treatment of stage II and III colon cancer has undergone a revolutionary transformation with the advent of MRD testing after surgery. A decade ago, the concept of using a post-surgical test instead of stage and pathology to determine the need for adjuvant chemotherapy was disruptive. Today, a blood test may be more informative of the need for chemotherapy than the stage at diagnosis. CONCLUSION Biomarker research is not just improving, but bringing a transformative change to CRC clinical management. Early detection is not just getting better, but improving thanks to a multi-modality approach, and personalized treatment plans are not just becoming a reality, but a promising future with MRD testing.
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Affiliation(s)
- Alessandro Mannucci
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute at City of Hope, Monrovia, CA, USA
- Gastroenterology and Gastrointestinal Endoscopy Unit, Vita-Salute San Raffaele University, IRCCS San Raffaele Hospital, Milan, Italy
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute at City of Hope, Monrovia, CA, USA.
- City of Hope Comprehensive Cancer Center, Duarte, CA, USA.
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Barbo M, Glavač D, Jezernik G, Ravnik-Glavač M. MicroRNAs as Biomarkers in Spinal Muscular Atrophy. Biomedicines 2024; 12:2428. [PMID: 39594995 PMCID: PMC11592373 DOI: 10.3390/biomedicines12112428] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2024] [Revised: 10/21/2024] [Accepted: 10/22/2024] [Indexed: 11/28/2024] Open
Abstract
Spinal muscular atrophy (SMA) is a severe neurodegenerative disease caused by the loss of the survival motor neuron (SMN) protein, leading to degeneration of anterior motor neurons and resulting in progressive muscle weakness and atrophy. Given that SMA has a single, well-defined genetic cause, gene-targeted therapies have been developed, aiming to increase SMN production in SMA patients. The SMN protein is likely involved in the synthesis of microRNAs (miRNAs), and dysregulated miRNA expression is increasingly associated with the pathophysiology of SMA. Currently, there is a lack of reliable biomarkers to monitor SMA; therefore, the search for novel SMA biomarkers, including miRNAs, is crucial as reliable tools are needed to track disease progression, predict the response to therapy and understand the different clinical outcomes of available treatments. In this review, we compile data on miRNAs associated with SMA pathogenesis and their potential use as biomarkers. Based on current knowledge, the most frequently deregulated miRNAs between SMA patients and controls, as well as pre- and post-treatment in SMA patients, include miR-1-3p, miR-133a-3p, miR-133b, and miR-206. These findings offer promising possibilities for improving patient classification and monitoring disease progression and response to treatment. Additionally, these findings provide insights into the broader molecular mechanisms and networks of SMA that could inform the development of future therapeutic strategies.
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Affiliation(s)
- Maruša Barbo
- Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia;
| | - Damjan Glavač
- Center for Human Genetics & Pharmacogenomics, Faculty of Medicine, University of Maribor, SI-2000 Maribor, Slovenia; (D.G.); (G.J.)
- Department of Molecular Genetics, Institute of Pathology, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia
| | - Gregor Jezernik
- Center for Human Genetics & Pharmacogenomics, Faculty of Medicine, University of Maribor, SI-2000 Maribor, Slovenia; (D.G.); (G.J.)
| | - Metka Ravnik-Glavač
- Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana, SI-1000 Ljubljana, Slovenia;
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Chao CT, Chiang CK, Hung KY. Extracellular MicroRNAs as Potential Biomarkers for Frail Kidney Phenotype: Progresses and Precautions. Aging Dis 2024; 15:1474-1481. [PMID: 37611904 PMCID: PMC11272190 DOI: 10.14336/ad.2023.0818] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Accepted: 08/18/2023] [Indexed: 08/25/2023] Open
Abstract
Frailty describes the cumulative subtle health deficits leading to an increased vulnerability to insults among older individuals or disease-laden ones. The prevalence of frailty increases substantially and relentlessly over declining renal function. Frailty in patients with chronic kidney disease (CKD) carries kidney-specific risk factors, clinical correlates and outcomes associations, hence alternatively termed frail kidney phenotype by researchers. Pathogenetically, miRNAs participate extensively in the development and aggravation of frailty, including the occurrence of frail kidney phenotype in CKD patients. These understandings spark profound interest in discovering biomarkers for identifying this detrimental phenotype, and extracellular miRNAs emerge as potentially useful ones. Pilot studies identify promising miRNA candidates for evaluating intermediates and surrogates of frail kidney phenotype, and more are underway. Several potential miRNA species in biologic fluids, such as circulating miR-29b and miR-223 (as inflammatory markers), exosomal miR-16-5p, miR-17/92 cluster members, and miR-106-5p (for uremic vasculopathy), serum exosomal miR-203a-3p (for uremic sarcopenia) have been examined and can be promising choices. Nonetheless, there remains research gap in affirming the direct connections between specific miRNAs and frail kidney phenotype. This stems partially from multiple limitations less well acknowledged before. From this perspective, we further outline the limitations and precautions prior to validating specific extracellular miRNA(s) for this purpose, from the definition of frailty definition, the functional and tissue specificity of miRNAs, the severity of CKD, and various technical considerations. It is expected that more affirmative studies can be produced for extending the utility of extracellular miRNAs in predicting frail kidney phenotype.
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Affiliation(s)
- Chia-Ter Chao
- Nephrology division, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
- Nephrology division, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
- Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei, Taiwan.
- Nephrology division, Department of Internal Medicine, National Taiwan University Hospital BeiHu branch, Taipei, Taiwan.
- Center of Faculty Development, National Taiwan University College of Medicine, Taipei, Taiwan.
| | - Chih-Kang Chiang
- Graduate Institute of Toxicology, National Taiwan University College of Medicine, Taipei, Taiwan.
- Blood purification division, Department of Integrative Diagnostics and Therapeutics, National Taiwan University Hospital, Taipei, Taiwan.
| | - Kuan-Yu Hung
- Nephrology division, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
- Nephrology division, Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
- Nephrology division, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
- Department of Internal Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan.
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Magowan D, Abdulshafea M, Thompson D, Rajamoorthy SI, Owen R, Harris D, Prosser S. Blood-based biomarkers and novel technologies for the diagnosis of colorectal cancer and adenomas: a narrative review. Biomark Med 2024; 18:493-506. [PMID: 38900496 DOI: 10.1080/17520363.2024.2345583] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2024] [Accepted: 03/12/2024] [Indexed: 06/21/2024] Open
Abstract
Aim: Blood-based biomarkers have shown promise for diagnosing colorectal cancer (CRC) and adenomas (CRA). This review summarizes recent studies in this area. Methods: A literature search was undertaken for 01/01/2017-01/03/2023. Criteria included CRC, CRA, liquid-biopsy, blood-based tests and diagnosis. Results: 12,378 studies were reduced to 178 for data extraction. Sixty focused on proteomics, 53 on RNA species, 30 on cfDNA methylation, seven on antigens and autoantibodies and 28 on novel techniques. 169 case control and nine cohort studies. Number of participants ranged 100-54,297, mean age 58.26. CRC sensitivity and specificity ranged 9.10-100% and 20.40-100%, respectively. CRA sensitivity and specificity ranged 8.00-95.70% and 4.00-97.00%, respectively. Conclusion: Sensitive and specific blood-based tests exist for CRC and CRA. However, studies demonstrate heterogenous techniques and reporting quality. Further work should concentrate on validation and meta-analyzes.
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Affiliation(s)
- Drew Magowan
- Swansea University, Singleton Park, SA2 8PP, Swansea, UK
- Swansea Bay University Health Board, Department of General Surgery, Morriston Hospital, SA6 6NL, Swansea, UK
| | - Mansour Abdulshafea
- Swansea Bay University Health Board, Department of General Surgery, Morriston Hospital, SA6 6NL, Swansea, UK
| | - Dominic Thompson
- Swansea Bay University Health Board, Department of General Surgery, Morriston Hospital, SA6 6NL, Swansea, UK
| | - Shri-Ishvarya Rajamoorthy
- Swansea Bay University Health Board, Department of General Surgery, Morriston Hospital, SA6 6NL, Swansea, UK
| | - Rhiannon Owen
- Swansea University, Singleton Park, SA2 8PP, Swansea, UK
| | - Dean Harris
- Swansea University, Singleton Park, SA2 8PP, Swansea, UK
- Swansea Bay University Health Board, Department of General Surgery, Morriston Hospital, SA6 6NL, Swansea, UK
| | - Susan Prosser
- Swansea Bay University Health Board, Department of General Surgery, Morriston Hospital, SA6 6NL, Swansea, UK
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Ng L, Wong SKM, Li HS, Sin RWY, Man JHW, Lo OSH, Pang RWC, Foo DCC, Law WL. A Four-Gene Panel in Rectal Swab Samples as a Biomarker for Colorectal Cancer Screening. Cells 2024; 13:930. [PMID: 38891062 PMCID: PMC11171518 DOI: 10.3390/cells13110930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2024] [Revised: 05/21/2024] [Accepted: 05/23/2024] [Indexed: 06/20/2024] Open
Abstract
BACKGROUND The dysregulation of gene expression is one of the key molecular features of colorectal cancer (CRC) development. This study aimed to investigate whether such dysregulation is reflected in rectal swab specimens of CRC patients and to evaluate its potential as a non-invasive approach for screening. METHODS We compared the expression level of 14 CRC-associated genes in tumor and adjacent non-tumor tissue of CRC patients and examined the correlation of their levels in tissue with paired rectal swab specimens. The level of these 14 genes in rectal swab specimens was compared among patients with CRC or polyp and control subjects, and the diagnostic potential of each dysregulated gene and the gene panel were evaluated. RESULTS The expression of CXCR2, SAA, COX1, PPARδ, PPARγ, Groγ, IL8, p21, c-myc, CD44 and CSF1 was significantly higher in CRC, and there was a significant correlation in the levels of most of them between the CRC and rectal swab specimens. In the training study, we showed that CD44, IL8, CXCR2 and c-myc levels were significantly higher in the rectal swab specimens of the CRC patients. Such result was confirmed in the validation study. A panel of these four genes was developed, and ROC analysis showed that this four-gene panel could identify CRC patients with an AUC value of 0.83 and identify overall polyp and precancerous adenoma patients with AUC values of 0.6522 and 0.7322, respectively. Finally, the predictive study showed that the four-gene panel demonstrated sensitivities of 63.6%, 76.9% and 88.9% in identifying overall polyp, precancerous adenoma and CRC patients, respectively, whereas the specificity for normal subjects was 72.2%. CONCLUSION The expression of CRC-associated genes in rectal swab specimens reflects the dysregulation status in colorectal tissue, and the four-gene panel is a potential non-invasive biomarker for early precancerous adenoma and CRC screening.
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Affiliation(s)
- Lui Ng
- Department of Surgery, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; (S.K.-M.W.); (H.-S.L.); (R.W.-Y.S.); (J.H.-W.M.); (O.S.-H.L.); (R.W.-C.P.); (D.C.-C.F.)
| | | | | | | | | | | | | | | | - Wai-Lun Law
- Department of Surgery, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China; (S.K.-M.W.); (H.-S.L.); (R.W.-Y.S.); (J.H.-W.M.); (O.S.-H.L.); (R.W.-C.P.); (D.C.-C.F.)
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10
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Huang L, Ding W, Wu H, Zheng J. miR-497/195 Cluster Affects the Development of Colorectal Cancer by Targeting FRA1. Mol Biotechnol 2024; 66:1019-1030. [PMID: 38147235 DOI: 10.1007/s12033-023-01000-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 11/16/2023] [Indexed: 12/27/2023]
Abstract
The miR-497-195 cluster facilitates the occurrence and development of cancer. This study aims to investigate whether the miR-195-497 cluster could regulate the progression of colorectal cancer by regulating the common target gene, FOS-related antigen 1 (FRA1). Overexpression of the miR-195/497 vector was used to evaluate the effect of overexpression of miR-195-497 clusters on the biological behavior of colon cancer cells. In animal experiments, tumor growth and metastasis were recorded by constructing a nude mouse model of a subcutaneously implanted tumor. miR-195 and miR-497 were expressed to varying degrees in Caco-2, LoVo, and HT-29 cells. Overexpression of miR-195/497 and inhibition of FRA1 decreased HT-29 cell proliferation, inhibited cell invasion and migration, and promoted Epithelial-mesenchymal transition (EMT). In vivo experiments showed that the overexpression of miR-195/497 or inhibition of FRA1 inhibited tumor growth, affected EMT in tumor cells, and inhibited the expression of FRA1. Additionally, the aforementioned conditions had the best effect when used together. The miR-195-497 cluster can regulate the proliferation, EMT, invasion, and migration of colorectal cancer cells by regulating the common target gene FRA1, thereby affecting the development of colorectal cancer.
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Affiliation(s)
- Li Huang
- Hospital of Guizhou Panjiang Coal Power Group Co. Ltd, Panzhou, China
| | - Wanjun Ding
- Department of Oncology, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China
| | - Hongxue Wu
- Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuhan, 430060, Hubei, China
| | - Jia Zheng
- Hospital of Guizhou Panjiang Coal Power Group Co. Ltd, Panzhou, China.
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Lopes SR, Martins C, Santos IC, Teixeira M, Gamito É, Alves AL. Colorectal cancer screening: A review of current knowledge and progress in research. World J Gastrointest Oncol 2024; 16:1119-1133. [PMID: 38660635 PMCID: PMC11037045 DOI: 10.4251/wjgo.v16.i4.1119] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/28/2023] [Revised: 01/16/2024] [Accepted: 02/18/2024] [Indexed: 04/10/2024] Open
Abstract
Colorectal cancer (CRC) is one of the most prevalent malignancies worldwide, being the third most commonly diagnosed malignancy and the second leading cause of cancer-related deaths globally. Despite the progress in screening, early diagnosis, and treatment, approximately 20%-25% of CRC patients still present with metastatic disease at the time of their initial diagnosis. Furthermore, the burden of disease is still expected to increase, especially in individuals younger than 50 years old, among whom early-onset CRC incidence has been increasing. Screening and early detection are pivotal to improve CRC-related outcomes. It is well established that CRC screening not only reduces incidence, but also decreases deaths from CRC. Diverse screening strategies have proven effective in decreasing both CRC incidence and mortality, though variations in efficacy have been reported across the literature. However, uncertainties persist regarding the optimal screening method, age intervals and periodicity. Moreover, adherence to CRC screening remains globally low. In recent years, emerging technologies, notably artificial intelligence, and non-invasive biomarkers, have been developed to overcome these barriers. However, controversy exists over the actual impact of some of the new discoveries on CRC-related outcomes and how to effectively integrate them into daily practice. In this review, we aim to cover the current evidence surrounding CRC screening. We will further critically assess novel approaches under investigation, in an effort to differentiate promising innovations from mere novelties.
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Affiliation(s)
- Sara Ramos Lopes
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
| | - Claudio Martins
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
| | - Inês Costa Santos
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
| | - Madalena Teixeira
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
| | - Élia Gamito
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
| | - Ana Luisa Alves
- Department of Gastroenterology, Centro Hospitalar de Setúbal, Setúbal 2910-446, Portugal
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12
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Oh CK, Cho YS. Pathogenesis and biomarkers of colorectal cancer by epigenetic alteration. Intest Res 2024; 22:131-151. [PMID: 38295766 PMCID: PMC11079515 DOI: 10.5217/ir.2023.00115] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2023] [Revised: 11/16/2023] [Accepted: 12/29/2023] [Indexed: 05/12/2024] Open
Abstract
Colorectal cancer (CRC) ranks third in cancer incidence and stands as the second leading cause of cancer-related deaths globally. CRC tumorigenesis results from a cumulative set of genetic and epigenetic alterations, disrupting cancer-regulatory processes like cell proliferation, metabolism, angiogenesis, cell death, invasion, and metastasis. Key epigenetic modifications observed in cancers encompass abnormal DNA methylation, atypical histone modifications, and irregularities in noncoding RNAs, such as microRNAs and long noncoding RNAs. The advancement in genomic technologies has positioned these genetic and epigenetic shifts as potential clinical biomarkers for CRC patients. This review concisely covers the fundamental principles of CRC-associated epigenetic changes, and examines in detail their emerging role as biomarkers for early detection, prognosis, and treatment response prediction.
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Affiliation(s)
- Chang Kyo Oh
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Kangnam Sacred Heart Hospital, Hallym University College of Medicine, Seoul, Korea
| | - Young-Seok Cho
- Division of Gastroenterology, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
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13
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Tran C, Dinh P. Potential diagnostic value of serum microRNAs for 19 cancer types: a meta-analysis of bioinformatics data. J Biomol Struct Dyn 2024:1-14. [PMID: 38487855 DOI: 10.1080/07391102.2024.2328744] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2023] [Accepted: 03/05/2024] [Indexed: 03/29/2025]
Abstract
Cancer is the second most common cause of mortality worldwide, accounting for almost 10 million deaths in 2020. These deaths were partly due to delayed diagnosis that led to deferred treatment. Therefore, new diagnostic methods are necessary to enhance the accuracy of noninvasive cancer detection. The present study developed a microRNA (miRNA)-based serum diagnostic marker for detecting a wide range of cancers. The study involved 61,019 serum samples from 19 different cancer types. A miRNA prediction model was established through bioinformatics analysis of serum samples from various cancer pathologies and qRT-PCR results from studies in PubMed aligned to the analysis criteria. R software v.4.1.1 with the limma data analysis package was used for single gene expression series data series, and batchNormalize and robustRankAggreg were used to predict the changes in miRNA expression in multiple datasets. GO and KEGG analyses showed that these miRNAs play a role in cancer-related biological signaling pathways. Finally, the diagnostic capability of these miRNA biomarkers was assessed using area under the curve analysis. The study predicted that 7 miRNAs were upregulated and 10 miRNAs were downregulated in 19 different types of cancer. Some miRNAs showed significant differential expression in a specific cancer type. Additionally, downstream genes regulated by miRNAs focused on many cancer-related molecular signaling pathways. In this review, we summarize the current understanding of miRNAs in various cancers, with a particular focus on their potential as future noninvasive diagnostic biomarkers. The emphasis is on their capacity for achieving high accuracy and cost savings compared to conventional biomarkers.
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Affiliation(s)
- ChauMyThanh Tran
- College of Medicine and Pharmacy, Duy Tan University, Danang, Vietnam
| | - PhongSon Dinh
- College of Medicine and Pharmacy, Duy Tan University, Danang, Vietnam
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14
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Tenchov R, Sapra AK, Sasso J, Ralhan K, Tummala A, Azoulay N, Zhou QA. Biomarkers for Early Cancer Detection: A Landscape View of Recent Advancements, Spotlighting Pancreatic and Liver Cancers. ACS Pharmacol Transl Sci 2024; 7:586-613. [PMID: 38481702 PMCID: PMC10928905 DOI: 10.1021/acsptsci.3c00346] [Citation(s) in RCA: 5] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/03/2023] [Revised: 01/06/2024] [Accepted: 01/23/2024] [Indexed: 01/04/2025]
Abstract
Cancer is one of the leading causes of death worldwide. Early cancer detection is critical because it can significantly improve treatment outcomes, thus saving lives, reducing suffering, and lessening psychological and economic burdens. Cancer biomarkers provide varied information about cancer, from early detection of malignancy to decisions on treatment and subsequent monitoring. A large variety of molecular, histologic, radiographic, or physiological entities or features are among the common types of cancer biomarkers. Sizeable recent methodological progress and insights have promoted significant developments in the field of early cancer detection biomarkers. Here we provide an overview of recent advances in the knowledge related to biomolecules and cellular entities used for early cancer detection. We examine data from the CAS Content Collection, the largest human-curated collection of published scientific information, as well as from the biomarker datasets at Excelra, and analyze the publication landscape of recent research. We also discuss the evolution of key concepts and cancer biomarkers development pipelines, with a particular focus on pancreatic and liver cancers, which are known to be remarkably difficult to detect early and to have particularly high morbidity and mortality. The objective of the paper is to provide a broad overview of the evolving landscape of current knowledge on cancer biomarkers and to outline challenges and evaluate growth opportunities, in order to further efforts in solving the problems that remain. The merit of this review stems from the extensive, wide-ranging coverage of the most up-to-date scientific information, allowing unique, unmatched breadth of landscape analysis and in-depth insights.
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Affiliation(s)
- Rumiana Tenchov
- CAS,
a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | - Aparna K. Sapra
- Excelra
Knowledge Solutions Pvt. Ltd., Hyderabad-500039, India
| | - Janet Sasso
- CAS,
a division of the American Chemical Society, Columbus, Ohio 43210, United States
| | | | - Anusha Tummala
- Excelra
Knowledge Solutions Pvt. Ltd., Hyderabad-500039, India
| | - Norman Azoulay
- Excelra
Knowledge Solutions Pvt. Ltd., Hyderabad-500039, India
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15
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Coleman D, Kuwada S. miRNA as a Biomarker for the Early Detection of Colorectal Cancer. Genes (Basel) 2024; 15:338. [PMID: 38540397 PMCID: PMC10969835 DOI: 10.3390/genes15030338] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2024] [Revised: 02/26/2024] [Accepted: 03/03/2024] [Indexed: 06/14/2024] Open
Abstract
MicroRNAs (miRNAs) are short, non-coding RNA segments that can be detected in a variety of clinical samples, including serum, stool, and urine. While miRNAs were initially known for their effect on post-translational gene expression, the last decade of research has shown them to be promising biomarkers for the detection of many types of cancer. This paper explores the use of miRNA detection as a tool for colorectal cancer (CRC) screening. We discuss the current state of miRNA detection, compare it to the existing CRC screening tools, and highlight the advantages and drawbacks of this approach from a clinical and logistical perspective. Our research finds that miRNA-based tests for CRC show great potential, but that widespread clinical adoption will be conditional on future research overcoming key hurdles.
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Affiliation(s)
- David Coleman
- John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, Honolulu, HI 96813, USA
| | - Scott Kuwada
- John A. Burns School of Medicine, University of Hawaii, 651 Ilalo Street, Honolulu, HI 96813, USA
- University of Hawaii Cancer Center, 01 Ilalo Street, Honolulu, HI 96813, USA
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16
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Pandey S, Jain A, Vagha S. Insights Into Colorectal Carcinoma: A Comprehensive Review of MicroRNA Expression Patterns. Cureus 2024; 16:e56739. [PMID: 38650823 PMCID: PMC11033970 DOI: 10.7759/cureus.56739] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2024] [Accepted: 03/22/2024] [Indexed: 04/25/2024] Open
Abstract
Colorectal carcinoma (CRC) remains a significant contributor to cancer-related morbidity and mortality worldwide. MicroRNAs (miRNAs) have emerged as crucial regulators of gene expression and play critical roles in various biological processes, including carcinogenesis. This comprehensive review aims to elucidate the role of miRNAs in CRC by analyzing their expression patterns and functional implications. An extensive literature review identified dysregulated miRNAs associated with different stages of CRC progression, from initiation to metastasis. These miRNAs modulate key signaling pathways in tumor growth, invasion, and metastasis. Furthermore, we discuss the potential of miRNAs as diagnostic biomarkers and therapeutic targets in CRC management. Future research directions include elucidating the functional significance of dysregulated miRNAs using advanced experimental models and computational approaches and exploring the therapeutic potential of miRNA-based interventions in personalized treatment strategies for CRC patients. Collaboration among researchers, clinicians, and industry partners will be essential to translate these findings into clinically impactful interventions that improve patient outcomes in CRC.
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Affiliation(s)
- Shweta Pandey
- Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
| | - Akriti Jain
- Pathology, Delhi State Cancer Institute, Delhi, IND
| | - Sunita Vagha
- Pathology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education and Research, Wardha, IND
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17
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Al-Nakhle HH. Unraveling the Multifaceted Role of the miR-17-92 Cluster in Colorectal Cancer: From Mechanisms to Biomarker Potential. Curr Issues Mol Biol 2024; 46:1832-1850. [PMID: 38534736 DOI: 10.3390/cimb46030120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2024] [Revised: 02/23/2024] [Accepted: 02/26/2024] [Indexed: 03/28/2024] Open
Abstract
Colorectal cancer (CRC) is a complex disease driven by intricate mechanisms, making it challenging to understand and manage. The miR-17-92 cluster has gained significant attention in CRC research due to its diverse functions and crucial role in various aspects of the disease. This cluster, consisting of multiple individual miRNAs, influences critical processes like tumor initiation, angiogenesis, metastasis, and the epithelial-mesenchymal transition (EMT). Beyond its roles in tumorigenesis and progression, miR-17-92's dysregulation in CRC has substantial implications for diagnosis, prognosis, and treatment, including chemotherapy responsiveness. It also shows promise as a diagnostic and prognostic biomarker, offering insights into treatment responses and disease progression. This review provides a comprehensive overview of recent advancements and the context-dependent role of the miR-17-92 cluster in colorectal cancer, drawing from the latest high-quality published data. It summarizes the established mechanisms governing miR-17-92 expression and the molecular pathways under its influence. Furthermore, it examines instances where it functions as an oncogene or a tumor suppressor, elucidating how cellular contexts dictate its biological effects. Ultimately, miR-17-92 holds promise as a biomarker for prognosis and therapy response, as well as a potential target for cancer prevention and therapeutic interventions. In essence, this review underscores the multifaceted nature of miR-17-92 in CRC research, offering promising avenues for enhancing the management of CRC patients.
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Affiliation(s)
- Hakeemah H Al-Nakhle
- Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Al-Madinah Al-Monawarah 42353, Saudi Arabia
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18
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Igder S, Zamani M, Fakher S, Siri M, Ashktorab H, Azarpira N, Mokarram P. Circulating Nucleic Acids in Colorectal Cancer: Diagnostic and Prognostic Value. DISEASE MARKERS 2024; 2024:9943412. [PMID: 38380073 PMCID: PMC10878755 DOI: 10.1155/2024/9943412] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 04/26/2023] [Revised: 01/07/2024] [Accepted: 01/25/2024] [Indexed: 02/22/2024]
Abstract
Colorectal cancer (CRC) is the third most prevalent cancer in the world and the fourth leading cause of cancer-related mortality. DNA (cfDNA/ctDNA) and RNA (cfRNA/ctRNA) in the blood are promising noninvasive biomarkers for molecular profiling, screening, diagnosis, treatment management, and prognosis of CRC. Technological advancements that enable precise detection of both genetic and epigenetic abnormalities, even in minute quantities in circulation, can overcome some of these challenges. This review focuses on testing for circulating nucleic acids in the circulation as a noninvasive method for CRC detection, monitoring, detection of minimal residual disease, and patient management. In addition, the benefits and drawbacks of various diagnostic techniques and associated bioinformatics tools have been detailed.
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Affiliation(s)
- Somayeh Igder
- Department of Clinical Biochemistry, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mozhdeh Zamani
- Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
- Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Shima Fakher
- Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Morvarid Siri
- Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hassan Ashktorab
- Department of Medicine, Gastroenterology Division and Cancer Center, Howard University College of Medicine, Washington, DC, USA
| | - Negar Azarpira
- Autophagy Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Pooneh Mokarram
- Autophagy Research Center, Department of Biochemistry, Shiraz University of Medical Sciences, Shiraz, Iran
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19
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Bagheri R, Ghorbian M, Ghorbian S. Tumor circulating biomarkers in colorectal cancer. Cancer Treat Res Commun 2023; 38:100787. [PMID: 38194840 DOI: 10.1016/j.ctarc.2023.100787] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2023] [Revised: 12/11/2023] [Accepted: 12/21/2023] [Indexed: 01/11/2024]
Abstract
CRC is a major global health concern and is responsible for a significant number of cancer-related deaths each year. The successful treatment of CRC becomes more difficult when it goes undetected until it has advanced to a later stage. Diagnostic biomarkers can play a critical role in the early detection of CRC, which leads to improved patient outcomes and increased survival rates. It is important to develop reliable biomarkers for the early detection of CRC to enable timely diagnosis and treatment. To date, CRC detection methods such as endoscopy, blood, and stool tests are imperfect and often only identify cases in the later stages of the disease. To overcome these limitations, researchers are turning to molecular biomarkers as a promising avenue for improving CRC detection. Diagnostic information can be provided more reliably through a noninvasive approach using biomarkers such as mRNA, circulating cell-free DNA, micro-RNA, long non-coding RNA, and proteins. These biomarkers can be found in blood, tissue, feces, and volatile organic compounds. The identification of molecular biomarkers with high sensitivity and specificity for early detection of CRC that are safe, cost-effective, and easily measurable remains a significant challenge for researchers. In this article, we will explore the latest advancements in blood-based diagnostic biomarkers for CRC and their potential impact on improving patient survival rates.
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Affiliation(s)
- Raana Bagheri
- Department of Molecular Genetics, Ahar Branch, Islamic Azad University, Ahar, Iran
| | - Mohsen Ghorbian
- Department of Computer Engineering, Qom Branch, Islamic Azad University, Qom, Iran
| | - Saeid Ghorbian
- Department of Molecular Genetics, Ahar Branch, Islamic Azad University, Ahar, Iran.
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20
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Islam MS, Gopalan V, Lam AK, Shiddiky MJA. Current advances in detecting genetic and epigenetic biomarkers of colorectal cancer. Biosens Bioelectron 2023; 239:115611. [PMID: 37619478 DOI: 10.1016/j.bios.2023.115611] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 08/07/2023] [Accepted: 08/16/2023] [Indexed: 08/26/2023]
Abstract
Colorectal carcinoma (CRC) is the third most common cancer in terms of diagnosis and the second in terms of mortality. Recent studies have shown that various proteins, extracellular vesicles (i.e., exosomes), specific genetic variants, gene transcripts, cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and altered epigenetic patterns, can be used to detect, and assess the prognosis of CRC. Over the last decade, a plethora of conventional methodologies (e.g., polymerase chain reaction [PCR], direct sequencing, enzyme-linked immunosorbent assay [ELISA], microarray, in situ hybridization) as well as advanced analytical methodologies (e.g., microfluidics, electrochemical biosensors, surface-enhanced Raman spectroscopy [SERS]) have been developed for analyzing genetic and epigenetic biomarkers using both optical and non-optical tools. Despite these methodologies, no gold standard detection method has yet been implemented that can analyze CRC with high specificity and sensitivity in an inexpensive, simple, and time-efficient manner. Moreover, until now, no study has critically reviewed the advantages and limitations of these methodologies. Here, an overview of the most used genetic and epigenetic biomarkers for CRC and their detection methods are discussed. Furthermore, a summary of the major biological, technical, and clinical challenges and advantages/limitations of existing techniques is also presented.
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Affiliation(s)
- Md Sajedul Islam
- Cancer Molecular Pathology, School of Medicine & Dentistry, Griffith University, Gold Coast Campus, Southport, QLD, 4222, Australia; Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, 4222, Australia
| | - Vinod Gopalan
- Cancer Molecular Pathology, School of Medicine & Dentistry, Griffith University, Gold Coast Campus, Southport, QLD, 4222, Australia; Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, 4222, Australia.
| | - Alfred K Lam
- Cancer Molecular Pathology, School of Medicine & Dentistry, Griffith University, Gold Coast Campus, Southport, QLD, 4222, Australia; Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, 4222, Australia; Pathology Queensland, Gold Coast University Hospital, Southport, QLD, 4215, Australia
| | - Muhammad J A Shiddiky
- Rural Health Research Institute, Charles Sturt University, Orange, NSW, 2800, Australia.
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21
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Postwala H, Shah Y, Parekh PS, Chorawala MR. Unveiling the genetic and epigenetic landscape of colorectal cancer: new insights into pathogenic pathways. Med Oncol 2023; 40:334. [PMID: 37855910 DOI: 10.1007/s12032-023-02201-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2023] [Accepted: 09/19/2023] [Indexed: 10/20/2023]
Abstract
Colorectal cancer (CRC) is a complex disease characterized by genetic and epigenetic alterations, playing a crucial role in its development and progression. This review aims to provide insights into the emerging landscape of these alterations in CRC pathogenesis to develop effective diagnostic tools and targeted therapies. Genetic alterations in signaling pathways such as Wnt/β-catenin, and PI3K/Akt/mTOR are pivotal in CRC development. Genetic profiling has identified distinct molecular subtypes, enabling personalized treatment strategies. Epigenetic modifications, including DNA methylation and histone modifications, also contribute to CRC pathogenesis by influencing critical cellular processes through gene silencing or activation. Non-coding RNAs have emerged as essential players in epigenetic regulation and CRC progression. Recent research highlights the interplay between genetic and epigenetic alterations in CRC. Genetic mutations can affect epigenetic modifications, leading to dysregulated gene expression and signaling cascades. Conversely, epigenetic changes can modulate genetic expression, amplifying or dampening the effects of genetic alterations. Advancements in understanding pathogenic pathways have potential clinical applications. Identifying genetic and epigenetic markers as diagnostic and prognostic biomarkers promises more accurate risk assessment and early detection. Challenges remain, including validating biomarkers and developing robust therapeutic strategies through extensive research and clinical trials. The dynamic nature of genetic and epigenetic alterations necessitates a comprehensive understanding of their temporal and spatial patterns during CRC progression. In conclusion, the genetic and epigenetic landscape of CRC is increasingly being unraveled, providing valuable insights into its pathogenesis. Integrating genetic and epigenetic knowledge holds great potential for improving diagnostics, prognostics, and personalized therapies in CRC. Continued research efforts are vital to translate these findings into clinical practice, ultimately improving patient outcomes.
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Affiliation(s)
- Humzah Postwala
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Ahmedabad, 380009, Gujarat, India
| | - Yesha Shah
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Ahmedabad, 380009, Gujarat, India
| | - Priyajeet S Parekh
- AV Pharma LLC, 1545 University Blvd N Ste A, Jacksonville, Florida, 32211, USA
| | - Mehul R Chorawala
- Department of Pharmacology and Pharmacy Practice, L. M. College of Pharmacy, Opp. Gujarat University, Ahmedabad, 380009, Gujarat, India.
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22
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Link J, Thon C, Petkevicius V, Steponaitiene R, Malfertheiner P, Kupcinskas J, Link A. The Translational Impact of Plant-Derived Xeno-miRNA miR-168 in Gastrointestinal Cancers and Preneoplastic Conditions. Diagnostics (Basel) 2023; 13:2701. [PMID: 37627960 PMCID: PMC10453613 DOI: 10.3390/diagnostics13162701] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2023] [Revised: 07/30/2023] [Accepted: 08/08/2023] [Indexed: 08/27/2023] Open
Abstract
INTRODUCTION Diet is one of the most important factors contributing to the multistep process of carcinogenesis. The clinical relevance of exogenous food-derived xeno-microRNAs (miRNAs) in human diseases is poorly understood. In this study, we aimed to evaluate the potential clinical relevance of the xeno-miRNA miR-168 in the gastric mucosa along the preneoplastic conditions and gastric carcinogenesis. METHODS For a systematic analysis, we included stomach tissues from patients with different pathologies, including normal mucosa (N), chronic non-atrophic (CNAG) and atrophic gastritis (CAG) and intestinal metaplasia (IM) (n = 72), matched non-tumorous (NT) and tumorous (T) gastric cancer (GC) tissues (n = 81), matched colorectal cancer (CRC) tissues (n = 40), and colon mucosa and faeces from controls and IBD patients. RESULTS miR-168 was reproducibly detectable in all samples studied, with the highest levels in the proximal upper GI and in non-tumorous compared to tumorous tissues in both GC and CRC. There was no difference related to H. pylori positivity or inflammation grade, while higher miR-168 levels were observed in patients with moderate or severe AG/IM or OLGIM3/4. Survival analysis showed only a small, non-significant trend towards worse overall survival for patients with the highest to lowest miR-168 levels, while no differences were related to Lauren's classification. CONCLUSIONS Food-derived xeno miRNAs are reproducibly detectable in the gastric and colonic mucosa. Although the clinically relevant function remains to be elucidated, higher levels of miR-168 in patients with moderate and severe IM merit further investigation.
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Affiliation(s)
- Jastin Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, 39120 Magdeburg, Germany (C.T.); (P.M.)
| | - Cosima Thon
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, 39120 Magdeburg, Germany (C.T.); (P.M.)
| | - Vytenis Petkevicius
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania; (V.P.); (R.S.); (J.K.)
| | - Ruta Steponaitiene
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania; (V.P.); (R.S.); (J.K.)
| | - Peter Malfertheiner
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, 39120 Magdeburg, Germany (C.T.); (P.M.)
- Medical Department II, University Hospital, Ludwig-Maximilians-Universität, 80539 Munich, Germany
| | - Juozas Kupcinskas
- Department of Gastroenterology and Institute for Digestive Research, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania; (V.P.); (R.S.); (J.K.)
| | - Alexander Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University, 39120 Magdeburg, Germany (C.T.); (P.M.)
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23
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Wang H, Sun Y, Zhang Z, Yang X, Ning B, Senyushkin P, Bogdanov B, Zmaga G, Xue Y, Chi J, Xie H, Chen S, Wu T, Lian Z, Pan Q, Chen B, Tan Z, Pan X, Su M, Song Y. Molecular Recognition-Modulated Hetero-Assembly of Nanostructures for Visualizable and Portable Detection of Circulating miRNAs. Anal Chem 2023; 95:11769-11776. [PMID: 37489945 DOI: 10.1021/acs.analchem.3c01996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/26/2023]
Abstract
Biomolecular markers, particularly circulating microRNAs (miRNAs) play an important role in diagnosis, monitoring, and therapeutic intervention of cancers. However, existing detection strategies remain intricate, laborious, and far from being developed for point-of-care testing. Here, we report a portable colorimetric sensor that utilizes the hetero-assembly of nanostructures driven by base pairing and recognition for direct detection of miRNAs. Following hybridization, two sizes of nanoparticles modified with single-strand DNA can be robustly assembled into heterostructures with strong optical resonance, exhibiting distinct structure colors. Particularly, the large nanoparticles are first arranged into nanochains to enhance scattering signals of small nanoparticles, which allows for sensitive detection and quantification of miRNAs without the requirement of target extraction, amplification, and fluorescent labels. Furthermore, we demonstrate the high specificity and single-base selectivity of testing different miRNA samples, which shows great potential in the diagnosis, staging, and monitoring of cancers. These heterogeneous assembled nanostructures provide an opportunity to develop simple, fast, and convenient tools for miRNAs detection, which is suitable for many scenarios, especially in low-resource setting.
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Affiliation(s)
- Huadong Wang
- Key Laboratory of Green Printing, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China
- University of Chinese Academy of Sciences (UCAS), Beijing 100049, P. R. China
| | - Yali Sun
- School of Physics and Engineering, ITMO University, Saint Petersburg 197101, Russia
| | - Zeying Zhang
- Key Laboratory of Green Printing, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China
| | - Xu Yang
- Key Laboratory of Green Printing, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China
- University of Chinese Academy of Sciences (UCAS), Beijing 100049, P. R. China
| | - Bobing Ning
- Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, P. R. China
| | - Pavel Senyushkin
- School of Physics and Engineering, ITMO University, Saint Petersburg 197101, Russia
| | - Bogdan Bogdanov
- School of Physics and Engineering, ITMO University, Saint Petersburg 197101, Russia
| | - Georgii Zmaga
- School of Physics and Engineering, ITMO University, Saint Petersburg 197101, Russia
| | - Yonggan Xue
- Department of General Surgery, Chinese PLA General Hospital, Beijing 100853, P. R. China
| | - Jimei Chi
- Key Laboratory of Green Printing, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China
- University of Chinese Academy of Sciences (UCAS), Beijing 100049, P. R. China
| | - Hongfei Xie
- Key Laboratory of Green Printing, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China
- University of Chinese Academy of Sciences (UCAS), Beijing 100049, P. R. China
| | - Sisi Chen
- Key Laboratory of Green Printing, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China
- University of Chinese Academy of Sciences (UCAS), Beijing 100049, P. R. China
| | - Tingqing Wu
- Key Laboratory of Green Printing, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China
- University of Chinese Academy of Sciences (UCAS), Beijing 100049, P. R. China
| | - Zewei Lian
- Key Laboratory of Green Printing, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China
- University of Chinese Academy of Sciences (UCAS), Beijing 100049, P. R. China
| | - Qi Pan
- Key Laboratory of Green Printing, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China
| | - Bingda Chen
- Key Laboratory of Green Printing, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China
| | - Zhiyu Tan
- Key Laboratory of Green Printing, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China
- University of Chinese Academy of Sciences (UCAS), Beijing 100049, P. R. China
| | - Xiangyu Pan
- Key Laboratory of Green Printing, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China
- University of Chinese Academy of Sciences (UCAS), Beijing 100049, P. R. China
| | - Meng Su
- Key Laboratory of Green Printing, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China
| | - Yanlin Song
- Key Laboratory of Green Printing, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences (CAS), Beijing 100190, P. R. China
- University of Chinese Academy of Sciences (UCAS), Beijing 100049, P. R. China
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Zha B, Luo Y, Kamili M, Zha X. Non-coding RNAs and gastrointestinal cancers prognosis: an umbrella review of systematic reviews and meta-analyses of observational studies. Front Oncol 2023; 13:1193665. [PMID: 37546412 PMCID: PMC10399243 DOI: 10.3389/fonc.2023.1193665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2023] [Accepted: 07/03/2023] [Indexed: 08/08/2023] Open
Abstract
Aim Provide an overview and a systematic evaluation of the evidence quality on the association between non-coding RNAs (ncRNAs) and prognosis value for gastrointestinal cancers (GICs). Methods We searched the literature from three electronic databases: Pubmed, Embase, and Web of science, then carefully screened and extracted the primary information and results from the included articles. We use A measurable systematic review and meta-analysis evaluation tool (AMSTAR2) to evaluate the quality of methodology and then use the Grading of Recommendations Assessment 2, Development and Evaluation guideline (GRADE) make sure the reliability of the meta-analysis. Results Overall, 182 meta-analyses from 58 studies were included in this study. Most of these studies are of low or very low quality. Using the scoring tool, we found that only two meta-analyses were rated as high reliability, and 17 meta-analyses were rated as medium reliability. Conclusions Although ncRNA has good prognostic value in some studies, only a tiny amount of evidence is highly credible at present. More research is needed in the future. PROSPERO registration number CRD42022382296.
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Affiliation(s)
- Bowen Zha
- The Sixth Clinical Medical College, Capital Medical University, Beijing, China
| | - Yuxi Luo
- The First Clinical Medical College, Capital Medical University, Beijing, China
| | - Muladili Kamili
- The Sixth Clinical Medical College, Capital Medical University, Beijing, China
| | - Xiaqin Zha
- Department of Blood Purification, University Affiliated Second Hospital, Nanchang, China
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25
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Giannopoulou N, Constantinou C. Recent Developments in Diagnostic and Prognostic Biomarkers for Colorectal Cancer: A Narrative Review. Oncology 2023; 101:675-684. [PMID: 37364542 DOI: 10.1159/000531474] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/26/2023] [Accepted: 06/02/2023] [Indexed: 06/28/2023]
Abstract
BACKGROUND Colorectal cancer was reported as the second most common cause of cancer death worldwide, in the year 2020. This disease is an important public health problem considering its high incidence and mortality rates. SUMMARY The molecular events that lead to colorectal cancer include genetic and epigenetic abnormalities. Some of the most important molecular mechanisms involved include the APC/β-catenin pathway, the microsatellite pathway, and the CpG island hypermethylation. Evidence in the literature supports a role for the microbiota in the development of colon carcinogenesis, and specific microbes may contribute to or prevent carcinogenesis. Progress in prevention, screening, and management has improved the overall prognosis of the disease when diagnosed at an early stage; yet metastatic disease continues to have a poor long-term prognosis due to late-stage diagnosis and treatment failure. Biomarkers are a key tool for early detection and prognosis and aim to reduce morbidity and mortality associated with colorectal cancer. The main focus of this narrative review is to provide an update on the recent development of diagnostic and prognostic biomarkers in stool, blood, and tumor tissue samples. KEY MESSAGES The review focuses on recent investigations in microRNAs, cadherins, Piwi-interacting RNAs, circulating cell-free DNA, and microbiome biomarkers which can be applied for the diagnosis and prognosis of colorectal cancer.
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Affiliation(s)
- Nefeli Giannopoulou
- Department of Basic and Clinical Sciences, University of Nicosia Medical School, Nicosia, Cyprus
| | - Constantina Constantinou
- Department of Basic and Clinical Sciences, University of Nicosia Medical School, Nicosia, Cyprus
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26
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Zhang H, Zuo L, Li J, Geng Z, Ge S, Song X, Wang Y, Zhang X, Wang L, Zhao T, Deng M, Chai D, Wang Q, Yang Z, Liu Q, Qiu Q, He X, Yang Y, Ge Y, Wu R, Zheng L, Li J, Chen R, Sun J, Hu J. Construction of a fecal immune-related protein-based biomarker panel for colorectal cancer diagnosis: a multicenter study. Front Immunol 2023; 14:1126217. [PMID: 37313408 PMCID: PMC10258350 DOI: 10.3389/fimmu.2023.1126217] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Accepted: 05/09/2023] [Indexed: 06/15/2023] Open
Abstract
Purpose To explore fecal immune-related proteins that can be used for colorectal cancer (CRC) diagnosis. Patients and methods Three independent cohorts were used in present study. In the discovery cohort, which included 14 CRC patients and 6 healthy controls (HCs), label-free proteomics was applied to identify immune-related proteins in stool that could be used for CRC diagnosis. Exploring potential links between gut microbes and immune-related proteins by 16S rRNA sequencing. The abundance of fecal immune-associated proteins was verified by ELISA in two independent validation cohorts and a biomarker panel was constructed that could be used for CRC diagnosis. The validation cohort I included 192 CRC patients and 151 HCs from 6 different hospitals. The validation cohort II included 141 CRC patients, 82 colorectal adenoma (CRA) patients, and 87 HCs from another hospital. Finally, the expression of biomarkers in cancer tissues was verified by immunohistochemistry (IHC). Results In the discovery study, 436 plausible fecal proteins were identified. And among 67 differential fecal proteins (|log2 fold change| > 1, P< 0.01) that could be used for CRC diagnosis, 16 immune-related proteins with diagnostic value were identified. The 16S rRNA sequencing results showed a positive correlation between immune-related proteins and the abundance of oncogenic bacteria. In the validation cohort I, a biomarker panel consisting of five fecal immune-related proteins (CAT, LTF, MMP9, RBP4, and SERPINA3) was constructed based on the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression. The biomarker panel was found to be superior to hemoglobin in the diagnosis of CRC in both validation cohort I and validation cohort II. The IHC result showed that protein expression levels of these five immune-related proteins were significantly higher in CRC tissue than in normal colorectal tissue. Conclusion A novel biomarker panel consisting of fecal immune-related proteins can be used for the diagnosis of CRC.
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Affiliation(s)
- Hao Zhang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Lugen Zuo
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Department of Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Jing Li
- Department of Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Zhijun Geng
- Department of Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Sitang Ge
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Department of Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Xue Song
- Department of Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Yueyue Wang
- Department of Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Xiaofeng Zhang
- Department of Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Department of Central Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Lian Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Tianhao Zhao
- Department of Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Department of Gastroenterology, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Min Deng
- Department of Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Department of Gastroenterology, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Damin Chai
- Department of Pathology, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Qiusheng Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Zi Yang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Quanli Liu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Quanwei Qiu
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Xuxu He
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Yiqun Yang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
| | - Yuanyuan Ge
- Department of Colorectal Surgery, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China
| | - Rong Wu
- Department of General Surgery, Zhongda Hospital, Southeast University, Nanjing, China
| | - Lin Zheng
- Department of Clinical Laboratory, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
| | - Jianjun Li
- Department of General Surgery, The First Medical Center, Chinese PLA General Hospital, Beijing, China
| | - Runkai Chen
- Department of General Surgery, Chinese PLA General Hospital, Beijing, China
| | - Jialiang Sun
- Department of General Surgery, Shanghai Fengxian District Central Hospital, Shanghai, China
| | - Jianguo Hu
- Department of Inflammatory Bowel Disease Research Center, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
- Department of Clinical Laboratory, First Affiliated Hospital of Bengbu Medical College, Bengbu, China
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Pecere S, Ciuffini C, Chiappetta MF, Petruzziello L, Papparella LG, Spada C, Gasbarrini A, Barbaro F. Increasing the accuracy of colorectal cancer screening. Expert Rev Anticancer Ther 2023; 23:583-591. [PMID: 37099725 DOI: 10.1080/14737140.2023.2207828] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/28/2023]
Abstract
INTRODUCTION Colorectal cancer (CRC) is a major health issue, being responsible for nearly 10% of all cancer-related deaths. Since CRC is often an asymptomatic or paucisymptomatic disease until it reaches advanced stages, screening is crucial for the diagnosis of preneoplastic lesions or early CRC. AREAS COVERED The aim of this review is to summarize the literature evidence on currently available CRC screening tools, with their pros and cons, focusing on the level of accuracy reached by each test over time. We also provide an overview of novel technologies and scientific advances that are currently being investigated and that in the future may represent real game-changers in the field of CRC screening. EXPERT OPINION We suggest that best screening modalities are annual or biennial FIT and colonoscopy every 10 years. We believe that the introduction of artificial intelligence (AI)-tools in the CRC screening field could lead to a significant improvement of the screening efficacy in reducing CRC incidence and mortality in the future. More resources should be put into implementing CRC programmes and support research project to further increase accuracy of CRC screening tests and strategies.
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Affiliation(s)
- Silvia Pecere
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Cristina Ciuffini
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Michele Francesco Chiappetta
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Lucio Petruzziello
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Luigi Giovanni Papparella
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Cristiano Spada
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Antonio Gasbarrini
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
| | - Federico Barbaro
- Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome
- Università Cattolica Del Sacro Cuore di Roma, Rome
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Chan FKL, Wong MCS, Chan AT, East JE, Chiu HM, Makharia GK, Weller D, Ooi CJ, Limsrivilai J, Saito Y, Hang DV, Emery JD, Makmun D, Wu K, Ali RAR, Ng SC. Joint Asian Pacific Association of Gastroenterology (APAGE)-Asian Pacific Society of Digestive Endoscopy (APSDE) clinical practice guidelines on the use of non-invasive biomarkers for diagnosis of colorectal neoplasia. Gut 2023:gutjnl-2023-329429. [PMID: 37019620 DOI: 10.1136/gutjnl-2023-329429] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 03/07/2023] [Indexed: 04/07/2023]
Abstract
Screening for colorectal cancer (CRC) is effective in reducing CRC related mortality. Current screening methods include endoscopy based and biomarker based approaches. This guideline is a joint official statement of the Asian Pacific Association of Gastroenterology (APAGE) and the Asian Pacific Society of Digestive Endoscopy (APSDE), developed in response to the increasing use of, and accumulating supportive evidence for the role of, non-invasive biomarkers for the diagnosis of CRC and its precursor lesions. A systematic review of 678 publications and a two stage Delphi consensus process involving 16 clinicians in various disciplines was undertaken to develop 32 evidence based and expert opinion based recommendations for the use of faecal immunochemical tests, faecal based tumour biomarkers or microbial biomarkers, and blood based tumour biomarkers for the detection of CRC and adenoma. Comprehensive up-to-date guidance is provided on indications, patient selection and strengths and limitations of each screening tool. Future research to inform clinical applications are discussed alongside objective measurement of research priorities. This joint APAGE-APSDE practice guideline is intended to provide an up-to-date guide to assist clinicians worldwide in utilising non-invasive biomarkers for CRC screening; it has particular salience for clinicians in the Asia-Pacific region.
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Affiliation(s)
- Francis K L Chan
- Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, People's Republic of China
| | - Martin C S Wong
- JC School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong, People's Republic of China
- Centre for Health Education and Health Promotion, The Chinese University of Hong Kong, Hong Kong, People's Republic of China
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA
| | - James E East
- Translational Gastroenterology Unit, Nuffield Department of Medicine, Oxford NIHR Biomedical Research Centre, John Radcliffe Hospital, University of Oxford, Oxford, UK
- Division of Gastroenterology and Hepatology, Mayo Clinic Healthcare, London, UK
| | - Han-Mo Chiu
- Department of Internal Medicine, College of Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - David Weller
- Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh Usher Institute of Population Health Sciences and Informatics, Edinburgh, UK
| | | | - Julajak Limsrivilai
- Internal Medicine, Mahidol University Faculty of Medicine Siriraj Hospital, Bangkok, Thailand
| | - Yutaka Saito
- Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
| | - Dao V Hang
- Hanoi Medical University, Hanoi, Vietnam
| | - Jon D Emery
- Department of General Practice, The University of Melbourne Faculty of Medicine Dentistry and Health Sciences, Melbourne, Victoria, Australia
| | | | - Kaichun Wu
- Xijing Hospital of Digestive Diseases, Xijing Hospital, Xian, China
| | | | - Siew C Ng
- Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, People's Republic of China
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29
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Liu J, Chen B, Yang M, Qian Y, Shen Q, Chen H, Dong Y, Wang L, Jiao J. A three-plasma miRNA panel predicts the risk of colorectal cancer: a community-based nested case‒control study. Sci Rep 2023; 13:4196. [PMID: 36918702 PMCID: PMC10014991 DOI: 10.1038/s41598-023-31449-3] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Accepted: 03/11/2023] [Indexed: 03/16/2023] Open
Abstract
Circulating microRNAs (miRNAs) have been considered potential markers for the early detection of malignant colorectal cancer (CRC). We aimed to identify a group of miRNAs for the early detection of CRC and assess their predictive ability in a community-based population in China. A nested case‒control study consisting of 97 incident colorectal cancer cases and 103 frequency-matched healthy controls was conducted. The data were randomly assigned into a training set (60%) and a test set (40%). We selected and detected 10 kinds of miRNAs in plasma samples. Multivariate logistic regression analysis was used to identify miRNAs associated with colorectal cancer risk in the training set and test set. Then, we evaluated the predictive ability of the identified miRNAs by the receiver operating characteristic curve (ROC). In this study, three miRNAs (miRNA-29a, miRNA-125b, miRNA-145) were significantly associated with colorectal cancer risk in both the training set and test set. The sensitivity of the identified miRNAs ranged from 0.854 to 0.961. After adding the identified miRNAs, the AUC (area under the curve) value significantly increased from 0.61 to 0.71 compared with the basic model consisting of only basic demographic information. We identified a three-plasma miRNA signature that may serve as a novel non-invasive biomarker in early CRC detection and in predicting individual CRC risk in the generation population.
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Affiliation(s)
- Jia Liu
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.,Department of Health Promotion & Chronic Non-Communicable Disease Control, Wuxi Center for Disease Control and Prevention (The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University), Wuxi, Jiangsu, China
| | - Binglin Chen
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China
| | - Man Yang
- Department of Health Promotion & Chronic Non-Communicable Disease Control, Wuxi Center for Disease Control and Prevention (The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University), Wuxi, Jiangsu, China
| | - Yun Qian
- Department of Health Promotion & Chronic Non-Communicable Disease Control, Wuxi Center for Disease Control and Prevention (The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University), Wuxi, Jiangsu, China
| | - Qian Shen
- Department of Health Promotion & Chronic Non-Communicable Disease Control, Wuxi Center for Disease Control and Prevention (The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University), Wuxi, Jiangsu, China
| | - Hai Chen
- Department of Health Promotion & Chronic Non-Communicable Disease Control, Wuxi Center for Disease Control and Prevention (The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University), Wuxi, Jiangsu, China
| | - Yunqiu Dong
- Department of Health Promotion & Chronic Non-Communicable Disease Control, Wuxi Center for Disease Control and Prevention (The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University), Wuxi, Jiangsu, China
| | - Lu Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China. .,Department of Health Promotion & Chronic Non-Communicable Disease Control, Wuxi Center for Disease Control and Prevention (The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University), Wuxi, Jiangsu, China.
| | - Jiandong Jiao
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China. .,Department of Health Promotion & Chronic Non-Communicable Disease Control, Wuxi Center for Disease Control and Prevention (The Affiliated Wuxi Center for Disease Control and Prevention of Nanjing Medical University), Wuxi, Jiangsu, China.
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30
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Sievänen T, Korhonen T, Jokela T, Ahtiainen M, Lahtinen L, Kuopio T, Lepistö A, Sillanpää E, Mecklin J, Seppälä TT, Laakkonen EK. Systemic circulating microRNA landscape in Lynch syndrome. Int J Cancer 2023; 152:932-944. [PMID: 36282188 PMCID: PMC10092425 DOI: 10.1002/ijc.34338] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2022] [Revised: 09/02/2022] [Accepted: 10/07/2022] [Indexed: 01/06/2023]
Abstract
Circulating microRNAs (c-miRs) are small noncoding RNA molecules that migrate throughout the body and regulate gene expression. Global c-miR expression patterns (c-miRnomes) change with sporadic carcinogenesis and have predictive potential in early detection of cancers. However, there are no studies that have assessed whether c-miRnomes display similar potential in carriers of inherited pathogenic mismatch-repair gene variants (path_MMR), known as Lynch syndrome (LS), who are predisposed to highly increased cancer risk. Using high-throughput sequencing and bioinformatic approaches, we conducted an exploratory analysis to characterize systemic c-miRnomes of path_MMR carriers, sporadic rectal cancer patients and non-LS controls. We showed for the first time that cancer-free path_MMR carriers have a systemic c-miRnome of 40 differentially expressed c-miRs that can distinguish them from non-LS controls. The systemic c-miRnome of cancer-free path_MMR carriers also resembles the systemic c-miRnomes of cancer patients with or without path_MMR. Our pathway analysis linked the found differentially expressed c-miRs to carcinogenesis. A total of 508 putative target genes were identified for 32 out of 40 differentially expressed c-miRs, and 238 of them were enriched in cancer-related pathways. The most enriched c-miR-target genes include well-known oncogenes and tumor suppressor genes such as BCL2, AKT3, PIK3CA, KRAS, NRAS, CDKN1A and PIK3R1. Taken together, our findings suggest that LS and sporadic carcinogenesis share common biological pathways and alterations in these pathways can produce a c-miR signature which can track potential oncogenic stress in cancer-free path_MMR carriers. Therefore, c-miRs hold potential in monitoring the LS risk stratification patterns during clinical surveillance or cancer management.
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Affiliation(s)
- Tero Sievänen
- Gerontology Research Center and Faculty of Sport and Health SciencesUniversity of JyväskyläJyväskyläFinland
| | - Tia‐Marje Korhonen
- Gerontology Research Center and Faculty of Sport and Health SciencesUniversity of JyväskyläJyväskyläFinland
| | - Tiina Jokela
- Gerontology Research Center and Faculty of Sport and Health SciencesUniversity of JyväskyläJyväskyläFinland
| | - Maarit Ahtiainen
- Department of Education and ResearchCentral Finland Health Care DistrictJyväskyläFinland
| | - Laura Lahtinen
- Department of PathologyCentral Finland Health Care DistrictJyväskyläFinland
| | - Teijo Kuopio
- Department of PathologyCentral Finland Health Care DistrictJyväskyläFinland
- Department of Biological and Environmental ScienceUniversity of JyväskyläJyväskyläFinland
| | - Anna Lepistö
- Department of Surgery, Abdominal CenterHelsinki University HospitalHelsinkiFinland
| | - Elina Sillanpää
- Gerontology Research Center and Faculty of Sport and Health SciencesUniversity of JyväskyläJyväskyläFinland
- Institute for Molecular Medicine Finland, University of HelsinkiHelsinkiFinland
| | - Jukka‐Pekka Mecklin
- Department of SurgeryCentral Finland Health Care DistrictJyväskyläFinland
- Faculty of Sport and Health SciencesUniversity of JyväskyläJyväskyläFinland
| | - Toni T. Seppälä
- Department of Surgery, Abdominal CenterHelsinki University HospitalHelsinkiFinland
- Applied Tumor Genomics Research ProgramUniversity of HelsinkiHelsinkiFinland
| | - Eija K. Laakkonen
- Gerontology Research Center and Faculty of Sport and Health SciencesUniversity of JyväskyläJyväskyläFinland
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Bahramy A, Zafari N, Rajabi F, Aghakhani A, Jayedi A, Khaboushan AS, Zolbin MM, Yekaninejad MS. Prognostic and diagnostic values of non-coding RNAs as biomarkers for breast cancer: An umbrella review and pan-cancer analysis. Front Mol Biosci 2023; 10:1096524. [PMID: 36726376 PMCID: PMC9885171 DOI: 10.3389/fmolb.2023.1096524] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2022] [Accepted: 01/06/2023] [Indexed: 01/19/2023] Open
Abstract
Background: Breast cancer (BC) is the most common cancer in women. The incidence and morbidity of BC are expected to rise rapidly. The stage at which BC is diagnosed has a significant impact on clinical outcomes. When detected early, an overall 5-year survival rate of up to 90% is possible. Although numerous studies have been conducted to assess the prognostic and diagnostic values of non-coding RNAs (ncRNAs) in breast cancer, their overall potential remains unclear. In this field of study, there are various systematic reviews and meta-analysis studies that report volumes of data. In this study, we tried to collect all these systematic reviews and meta-analysis studies in order to re-analyze their data without any restriction to breast cancer or non-coding RNA type, to make it as comprehensive as possible. Methods: Three databases, namely, PubMed, Scopus, and Web of Science (WoS), were searched to find any relevant meta-analysis studies. After thoroughly searching, the screening of titles, abstracts, and full-text and the quality of all included studies were assessed using the AMSTAR tool. All the required data including hazard ratios (HRs), sensitivity (SENS), and specificity (SPEC) were extracted for further analysis, and all analyses were carried out using Stata. Results: In the prognostic part, our initial search of three databases produced 10,548 articles, of which 58 studies were included in the current study. We assessed the correlation of non-coding RNA (ncRNA) expression with different survival outcomes in breast cancer patients: overall survival (OS) (HR = 1.521), disease-free survival (DFS) (HR = 1.33), recurrence-free survival (RFS) (HR = 1.66), progression-free survival (PFS) (HR = 1.71), metastasis-free survival (MFS) (HR = 0.90), and disease-specific survival (DSS) (HR = 0.37). After eliminating low-quality studies, the results did not change significantly. In the diagnostic part, 22 articles and 30 datasets were retrieved from 8,453 articles. The quality of all studies was determined. The bivariate and random-effects models were used to assess the diagnostic value of ncRNAs. The overall area under the curve (AUC) of ncRNAs in differentiated patients is 0.88 (SENS: 80% and SPEC: 82%). There was no difference in the potential of single and combined ncRNAs in differentiated BC patients. However, the overall potential of microRNAs (miRNAs) is higher than that of long non-coding RNAs (lncRNAs). No evidence of publication bias was found in the current study. Nine miRNAs, four lncRNAs, and five gene targets showed significant OS and RFS between normal and cancer patients based on pan-cancer data analysis, demonstrating their potential prognostic value. Conclusion: The present umbrella review showed that ncRNAs, including lncRNAs and miRNAs, can be used as prognostic and diagnostic biomarkers for breast cancer patients, regardless of the sample sources, ethnicity of patients, and subtype of breast cancer.
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Affiliation(s)
- Afshin Bahramy
- Pediatric Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Narges Zafari
- Pediatric Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Rajabi
- Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
| | - Amirhossein Aghakhani
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Ahmad Jayedi
- Social Determinants of Health Research Center, Semnan University of Medical Sciences, Semnan, Iran
| | - Alireza Soltani Khaboushan
- Pediatric Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran,Students’ Scientific Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Masoumeh Majidi Zolbin
- Pediatric Urology and Regenerative Medicine Research Center, Gene, Cell and Tissue Research Institute, Children’s Medical Center, Tehran University of Medical Sciences, Tehran, Iran,*Correspondence: Mir Saeed Yekaninejad, , ; Masoumeh Majidi Zolbin, ,
| | - Mir Saeed Yekaninejad
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran,*Correspondence: Mir Saeed Yekaninejad, , ; Masoumeh Majidi Zolbin, ,
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Losurdo P, Gandin I, Belgrano M, Fiorese I, Verardo R, Zanconati F, Cova MA, de Manzini N. microRNAs combined to radiomic features as a predictor of complete clinical response after neoadjuvant radio-chemotherapy for locally advanced rectal cancer: a preliminary study. Surg Endosc 2023; 37:3676-3683. [PMID: 36639577 DOI: 10.1007/s00464-022-09851-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 12/27/2022] [Indexed: 01/15/2023]
Abstract
OBJECTIVE To define a predictive Artificial Intelligence (AI) algorithm based on the integration of a set of biopsy-based microRNAs expression data and radiomic features to understand their potential impact in predicting clinical response (CR) to neoadjuvant radio-chemotherapy (nRCT). The identification of patients who would truly benefit from nRCT for Locally Advanced Rectal Cancer (LARC) could be crucial for an improvement in a tailored therapy. METHODS Forty patients with LARC were retrospectively analyzed. An MRI of the pelvis before and after nRCT was performed. In the diagnostic biopsy, the expression levels of 7 miRNAs were measured and correlated with the tumor response rate (TRG), assessed on the surgical sample. The accuracy of complete CR (cCR) prediction was compared for i) clinical predictors; ii) radiomic features; iii) miRNAs levels; and iv) combination of radiomics and miRNAs. RESULTS Clinical predictors showed the lowest accuracy. The best performing model was based on the integration of radiomic features with miR-145 expression level (AUC-ROC = 0.90). AI algorithm, based on radiomics features and the overexpression of miR-145, showed an association with the TRG class and demonstrated a significant impact on the outcome. CONCLUSION The pre-treatment identification of responders/NON-responders to nRCT could address patients to a personalized strategy, such as total neoadjuvant therapy (TNT) for responders and upfront surgery for non-responders. The combination of radiomic features and miRNAs expression data from images and biopsy obtained through standard of care has the potential to accelerate the discovery of a noninvasive multimodal approach to predict the cCR after nRCT for LARC.
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Affiliation(s)
- Pasquale Losurdo
- Surgical Clinic Unit, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy.
| | - Ilaria Gandin
- Biostatistics Unit, Department of Medical and Surgical Sciences, University of Trieste, Strada Di Fiume 447, 34149, Trieste, Italy
| | - Manuel Belgrano
- Radiology Unit, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy
| | - Ilaria Fiorese
- Radiology Unit, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy
| | - Roberto Verardo
- LNCIB - Consorzio Interuniversitario per le Biotecnologie c/o BIC Incubatori FVG, Srl - Via Flavia 23/1, 34149, Trieste, Italy
| | - Fabrizio Zanconati
- Pathology Unit, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy
| | - Maria Assunta Cova
- Radiology Unit, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy
| | - Nicolò de Manzini
- Surgical Clinic Unit, Department of Medical and Surgical Sciences, Hospital of Cattinara, University of Trieste, Strada di Fiume 447, 34149, Trieste, Italy
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Mirza S, Bhadresha K, Mughal MJ, McCabe M, Shahbazi R, Ruff P, Penny C. Liquid biopsy approaches and immunotherapy in colorectal cancer for precision medicine: Are we there yet? Front Oncol 2023; 12:1023565. [PMID: 36686736 PMCID: PMC9853908 DOI: 10.3389/fonc.2022.1023565] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 12/08/2022] [Indexed: 01/07/2023] Open
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally, with nearly half of patients detected in the advanced stages. This is due to the fact that symptoms associated with CRC often do not appear until the cancer has reached an advanced stage. This suggests that CRC is a cancer with a slow progression, making it curable and preventive if detected in its early stage. Therefore, there is an urgent clinical need to improve CRC early detection and personalize therapy for patients with this cancer. Recently, liquid biopsy as a non-invasive or nominally invasive approach has attracted considerable interest for its real-time disease monitoring capability through repeated sample analysis. Several studies in CRC have revealed the potential for liquid biopsy application in a real clinical setting using circulating RNA/miRNA, circulating tumor cells (CTCs), exosomes, etc. However, Liquid biopsy still remains a challenge since there are currently no promising results with high specificity and specificity that might be employed as optimal circulatory biomarkers. Therefore, in this review, we conferred the plausible role of less explored liquid biopsy components like mitochondrial DNA (mtDNA), organoid model of CTCs, and circulating cancer-associated fibroblasts (cCAFs); which may allow researchers to develop improved strategies to unravel unfulfilled clinical requirements in CRC patients. Moreover, we have also discussed immunotherapy approaches to improve the prognosis of MSI (Microsatellite Instability) CRC patients using neoantigens and immune cells in the tumor microenvironment (TME) as a liquid biopsy approach in detail.
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Affiliation(s)
- Sheefa Mirza
- Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa,Department of Internal Medicine, Common Epithelial Cancer Research Centre, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Kinjal Bhadresha
- Hematology/Oncology Division, School of Medicine, Indiana University, Indianapolis, IN, United States
| | - Muhammed Jameel Mughal
- Department of Biochemistry and Molecular Medicine, School of Medicine and Health Science, The George Washington University, Washington, DC, United States
| | - Michelle McCabe
- Department of Anatomical Pathology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg, South Africa
| | - Reza Shahbazi
- Hematology/Oncology Division, School of Medicine, Indiana University, Indianapolis, IN, United States
| | - Paul Ruff
- Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa,Department of Internal Medicine, Common Epithelial Cancer Research Centre, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Clement Penny
- Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa,Department of Internal Medicine, Common Epithelial Cancer Research Centre, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa,*Correspondence: Clement Penny,
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Yoshikawa Y, Fukunaga M, Takahashi J, Shimizu D, Masuda T, Mizushima T, Yamada K, Mori M, Eguchi H, Doki Y, Ochiya T, Mimori K. Identification of the Minimum Combination of Serum microRNAs to Predict the Recurrence of Colorectal Cancer Cases. Ann Surg Oncol 2023; 30:233-243. [PMID: 36175711 PMCID: PMC9726799 DOI: 10.1245/s10434-022-12355-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Accepted: 07/08/2022] [Indexed: 12/14/2022]
Abstract
BACKGROUND Serum microRNAs (miRNAs) have been recognized as potential stable biomarkers for various types of cancer. Considering the clinical applications, there are certain critical requirements, such as minimizing the number of miRNAs, reproducibility in a longitudinal clinical course, and superiority to conventional tumor markers, such as carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9. This study aimed to identify serum miRNAs that indicate the recurrence of colorectal cancer (CRC), surpassing inter-tumor heterogeneity. METHODS We conducted an analysis of 434 serum samples from 91 patients with CRC and 71 healthy subjects. miRNAs were obtained from Toray Co., Ltd, and miRNA profiles were analyzed using a three-step approach. miRNAs that were highly expressed in patients with CRC than in the healthy controls in the screening phase, and those that were highly expressed in the preoperative samples than in the 1-month postoperative samples in the discovery phase, were extracted. In the validation phase, the extracted miRNAs were evaluated in 323 perioperative samples, in chronological order. RESULTS A total of 12 miRNAs (miR-25-3p, miR-451a, miR-1246, miR-1268b, miR-2392, miR-4480, miR-4648, miR-4732-5p, miR-4736, miR-6131, miR-6776-5p, and miR-6851-5p) were significantly concordant with the clinical findings of tumor recurrence, however their ability to function as biomarkers was comparable with CEA. In contrast, the combination of miR-1246, miR-1268b, and miR-4648 demonstrated a higher area under the curve (AUC) than CEA. These three miRNAs were upregulated in primary CRC tissues. CONCLUSION We identified ideal combinatorial miRNAs to predict CRC recurrence.
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Affiliation(s)
- Yukihiro Yoshikawa
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita Japan ,Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka Japan
| | | | - Junichi Takahashi
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita Japan
| | - Dai Shimizu
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita Japan
| | - Takaaki Masuda
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita Japan
| | - Tsunekazu Mizushima
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka Japan
| | - Kazutaka Yamada
- Coloproctology Center Takano Hospital, Kumamoto, Kumamoto Japan
| | - Masaki Mori
- Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Hidetoshi Eguchi
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka Japan
| | - Yuichiro Doki
- Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, Suita, Osaka Japan
| | - Takahiro Ochiya
- Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan
| | - Koshi Mimori
- Department of Surgery, Kyushu University Beppu Hospital, Beppu, Oita Japan
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Sabbaghian A, Mussack V, Kirchner B, Bui MLU, Kalani MR, Pfaffl MW, Golalipour M. A panel of blood-derived miRNAs with a stable expression pattern as a potential pan-cancer detection signature. Front Mol Biosci 2022; 9:1030749. [PMID: 36589227 PMCID: PMC9798419 DOI: 10.3389/fmolb.2022.1030749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2022] [Accepted: 11/30/2022] [Indexed: 12/23/2022] Open
Abstract
Introduction: MicroRNAs have a significant role in the regulation of the transcriptome. Several miRNAs have been proposed as potential biomarkers in different malignancies. However, contradictory results have been reported on the capability of miRNA biomarkers in cancer detection. The human biological clock involves molecular mechanisms that regulate several genes over time. Therefore, the sampling time becomes one of the significant factors in gene expression studies. Method: In the present study, we have tried to find miRNAs with minimum fluctuation in expression levels at different time points that could be more accurate candidates as diagnostic biomarkers. The small RNA-seq raw data of ten healthy individuals across nine-time points were analyzed to identify miRNAs with stable expression. Results: We have found five oscillation patterns. The stable miRNAs were investigated in 779 small-RNA-seq datasets of eleven cancer types. All miRNAs with the highest differential expression were selected for further analysis. The selected miRNAs were explored for functional pathways. The predominantly enriched pathways were miRNA in cancer and the P53-signaling pathway. Finally, we have found seven miRNAs, including miR-142-3p, miR-199a-5p, miR-223-5p, let-7d-5p, miR-148b-3p, miR-340-5p, and miR-421. These miRNAs showed minimum fluctuation in healthy blood and were dysregulated in the blood of eleven cancer types. Conclusion: We have found a signature of seven stable miRNAs which dysregulate in several cancer types and may serve as potential pan-cancer biomarkers.
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Affiliation(s)
- Amir Sabbaghian
- Department of Molecular Medicine, Advanced Technologies Faculty, Golestan University of Medical Science, Gorgan, Iran
| | - Veronika Mussack
- Department of Animal Physiology and Immunology, TUM School of Life Sciences, Technical University of Munich, Munich, Germany
| | - Benedikt Kirchner
- Department of Animal Physiology and Immunology, TUM School of Life Sciences, Technical University of Munich, Munich, Germany
| | - Maria L. U. Bui
- Department of Animal Physiology and Immunology, TUM School of Life Sciences, Technical University of Munich, Munich, Germany
| | - Mohammad Reza Kalani
- Department of Molecular Medicine, Advanced Technologies Faculty, Golestan University of Medical Science, Gorgan, Iran
| | - Michael W. Pfaffl
- Department of Animal Physiology and Immunology, TUM School of Life Sciences, Technical University of Munich, Munich, Germany
| | - Masoud Golalipour
- Department of Molecular Medicine, Advanced Technologies Faculty, Golestan University of Medical Science, Gorgan, Iran
- Cellular and Molecular Research Center, Golestan University of Medical Science, Gorgan, Iran
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Loomans-Kropp HA. Multicancer early detection tests: where are we? JNCI Cancer Spectr 2022; 7:6858475. [PMID: 36453871 PMCID: PMC9825312 DOI: 10.1093/jncics/pkac084] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2022] [Revised: 11/23/2022] [Accepted: 11/26/2022] [Indexed: 12/05/2022] Open
Affiliation(s)
- Holli A Loomans-Kropp
- Correspondence to: Holli A. Loomans-Kropp, PhD, MPH, Division of Cancer Prevention and Control, Department of Internal Medicine, College of Medicine, The Ohio State University, 1590 N. High St., Suite 571 Columbus, OH 43201, USA (e-mail: )
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Shekari S, Fathi S, Roumi Z, Akbari ME, Tajadod S, Afsharfar M, Hasanpour Ardekanizadeh N, Bourbour F, Keshavarz SA, Sotoudeh M, Gholamalizadeh M, Nemat Gorgani S, Shafaei Kachaei H, Alizadeh A, Doaei S. Association between dietary intake of fatty acids and colorectal cancer, a case-control study. Front Nutr 2022; 9:856408. [PMID: 36263307 PMCID: PMC9576465 DOI: 10.3389/fnut.2022.856408] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Accepted: 09/12/2022] [Indexed: 11/13/2022] Open
Abstract
Background The association of dietary fat and colorectal cancer (CRC) was frequently reported. However, few studies assessed the effects of different types of dietary fats on CRC. This study aimed to investigate the association between intakes of different types of dietary fatty acids with colorectal cancer risk. Methods This case-control study was conducted on 480 participants including 160 CRC cases and 320 healthy controls in Firoozgar Hospital, Tehran, Iran. The intake of dietary fatty acids of the participants was assessed using a semi quantitative food frequency questionnaire (FFQ). Results The mean intake of cholesterol (273.07 ± 53.63 vs. 254.17 ± 61.12, P = 0.001), polyunsaturated fatty acids (PUFA) (16.54 ± 4.20 vs. 15.41 ± 4.44, P = 0.012), and calorie (2,568.76 ± 404.48 vs. 2,493.38 ± 176.03, P = 0.006) was higher and the mean intake of oleic acid (5.59 ± 3.17 vs. 8.21 ± 5.46) and linoleic acid (6.03 ± 3.44 vs. 7.02 ± 4.08, P = 0.01) was lower in the case group compared to the control group. An inverse association was found between colorectal cancer (CRC) and dietary intake of oleic acid (OR: 0.85, CI 95% 0.80–0.90, P = 0.001), linoleic acid (OR: 0.85, CI 95% 0.78–0.93, P = 0.001), and α-linolenic acid (OR: 0.75, CI 95% 0.57–0.98, P = 0.04). The association remained significant after adjusting for age and sex, sleep, smoking, and alcohol consumption, and BMI. Conclusions The results of this study support a protective effect of oleic acid, linoleic acid, and α-linolenic acid against CRC. Further longitudinal studies are warranted to confirm these results.
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Affiliation(s)
- Soheila Shekari
- Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Soroor Fathi
- Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zahra Roumi
- Department of Nutrition, Electronic Health and Statistics Surveillance Research Center, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | | | - Shirin Tajadod
- Department of Nutrition, School of Public Health, International Campus, Iran University of Medical Sciences, Tehran, Iran
| | - Maryam Afsharfar
- Department of Nutrition, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Naeemeh Hasanpour Ardekanizadeh
- Department of Clinical Nutrition, School of Nutrition and Food Sciences, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Fatemeh Bourbour
- Department of Clinical Nutrition and Dietetics, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Seyed Ali Keshavarz
- Department of Clinical Nutrition, School of Nutritional Sciences and Dietetic, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahtab Sotoudeh
- Department of Nutrition, Science and Research Branch, Islamic Azad University, Tehran, Iran
| | - Maryam Gholamalizadeh
- Cancer Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shiva Nemat Gorgani
- Department of Clinical Nutrition and Dietetics, Research Institute, Shahid Beheshti University of Medical Science, Tehran, Iran
| | | | - Atiyeh Alizadeh
- Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Science, Tehran, Iran
| | - Saeid Doaei
- Department of Community Nutrition, Faculty of Nutrition and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran,*Correspondence: Saeid Doaei
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Investigating the Role of Circulating miRNAs as Biomarkers in Colorectal Cancer: An Epidemiological Systematic Review. Biomedicines 2022; 10:biomedicines10092224. [PMID: 36140324 PMCID: PMC9496335 DOI: 10.3390/biomedicines10092224] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2022] [Revised: 09/01/2022] [Accepted: 09/03/2022] [Indexed: 11/20/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers worldwide. Primary and secondary preventions are key to reducing the global burden. MicroRNAs (miRNAs) are a group of small non-coding RNA molecules, which seem to have a role either as tumor suppressor genes or oncogenes and to be related to cancer risk factors, such as obesity and inflammation. We conducted a systematic review and meta-analysis to identify circulating miRNAs related to CRC diagnosis that could be selected as biomarkers in a meet-in-the-middle analysis. Forty-four studies were included in the systematic review and nine studies in the meta-analysis. The pooled sensitivity and specificity of miR-21 for CRC diagnosis were 77% (95% CI: 69–84) and 82% (95% CI: 70–90), respectively, with an AUC of 0.86 (95% CI: 0.82–0.88). Several miRNAs were found to be dysregulated, distinguishing patients with CRC from healthy controls. However, little consistency was present across the included studies, making it challenging to identify specific miRNAs, which were consistently validated. Understanding the mechanisms by which miRNAs become biologically embedded in cancer initiation and promotion may help better understand cancer pathways to develop more effective prevention strategies and therapy approaches.
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Wu H, Ganguly S, Tollefsbol TO. Modulating Microbiota as a New Strategy for Breast Cancer Prevention and Treatment. Microorganisms 2022; 10:microorganisms10091727. [PMID: 36144329 PMCID: PMC9503838 DOI: 10.3390/microorganisms10091727] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 08/23/2022] [Accepted: 08/25/2022] [Indexed: 11/18/2022] Open
Abstract
Breast cancer (BC) is the most common cancer in women in the United States. There has been an increasing incidence and decreasing mortality rate of BC cases over the past several decades. Many risk factors are associated with BC, such as diet, aging, personal and family history, obesity, and some environmental factors. Recent studies have shown that healthy individuals and BC patients have different microbiota composition, indicating that microbiome is a new risk factor for BC. Gut and breast microbiota alterations are associated with BC prognosis. This review will evaluate altered microbiota populations in gut, breast tissue, and milk of BC patients, as well as mechanisms of interactions between microbiota modulation and BC. Probiotics and prebiotics are commercially available dietary supplements to alleviate side-effects of cancer therapies. They also shape the population of human gut microbiome. This review evaluates novel means of modulating microbiota by nutritional treatment with probiotics and prebiotics as emerging and promising strategies for prevention and treatment of BC. The mechanistic role of probiotic and prebiotics partially depend on alterations in estrogen metabolism, systematic immune regulation, and epigenetics regulation.
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Affiliation(s)
- Huixin Wu
- Department of Biology, University of Alabama at Birmingham, 1300 University Boulevard, Birmingham, AL 35294, USA
| | - Sebanti Ganguly
- Department of Biology, University of Alabama at Birmingham, 1300 University Boulevard, Birmingham, AL 35294, USA
| | - Trygve O. Tollefsbol
- Department of Biology, University of Alabama at Birmingham, 1300 University Boulevard, Birmingham, AL 35294, USA
- Integrative Center for Aging Research, University of Alabama Birmingham, 1530 3rd Avenue South, Birmingham, AL 35294, USA
- O’Neal Comprehensive Cancer Center, University of Alabama Birmingham, 1802 6th Avenue South, Birmingham, AL 35294, USA
- Nutrition Obesity Research Center, University of Alabama Birmingham, 1675 University Boulevard, Birmingham, AL 35294, USA
- Comprehensive Diabetes Center, University of Alabama Birmingham, 1825 University Boulevard, Birmingham, AL 35294, USA
- University Wide Microbiome Center, University of Alabama Birmingham, 845 19th Street South, Birmingham, AL 35294, USA
- Correspondence: ; Tel.: +1-205-934-4573; Fax: +1-205-975-6097
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Raut JR, Bhardwaj M, Niedermaier T, Miah K, Schrotz-King P, Brenner H. Assessment of a Serum Microrna Risk Score for Colorectal Cancer among Participants of Screening Colonoscopy at Various Stages of Colorectal Carcinogenesis. Cells 2022; 11:cells11152462. [PMID: 35954306 PMCID: PMC9367813 DOI: 10.3390/cells11152462] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Revised: 07/29/2022] [Accepted: 08/01/2022] [Indexed: 11/20/2022] Open
Abstract
We recently derived and validated a serum-based microRNA risk score (miR-score) which predicted colorectal cancer (CRC) occurrence with very high accuracy within 14 years of follow-up in a large population-based cohort. Here, we aimed to assess and compare the distribution of the miR-score among participants of screening colonoscopy at various stages of colorectal carcinogenesis. MicroRNAs (miRNAs) were profiled by quantitative-real-time-polymerase-chain-reaction in the serum samples of screening colonoscopy participants with CRC (n = 52), advanced colorectal adenoma (AA, n = 100), non-advanced colorectal adenoma (NAA, n = 88), and participants free of colorectal neoplasms (n = 173). The mean values of the miR-score were compared between groups by the Mann–Whitney U test. The associations of the miR-score with risk for colorectal neoplasms were evaluated using logistic regression analyses. MicroRNA risk scores were significantly higher among participants with AA than among those with NAA (p = 0.027) and those with CRC (p = 0.014), whereas no statistically significant difference was seen between those with NAA and those with no colorectal neoplasms (p = 0.127). When comparing adjacent groups, miR-scores were inversely associated with CRC versus AA and positively associated with AA versus NAA [odds ratio (OR), 0.37 (95% confidence interval (CI), 0.16–0.86) and OR, 2.22 (95% CI, 1.06–4.64) for the top versus bottom tertiles, respectively]. Our results are consistent with the hypothesis that a high miR-score may be indicative of an increased CRC risk by an increased tendency of progression from non-advanced to advanced colorectal neoplasms, along with a change of the miR-patterns after CRC manifestation.
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Affiliation(s)
- Janhavi R. Raut
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Medical Faculty Heidelberg, University of Heidelberg, Im Neuenheimer Feld 672, 69120 Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
| | - Megha Bhardwaj
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Tobias Niedermaier
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Kaya Miah
- Division of Biostatistics, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
| | - Petra Schrotz-King
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
| | - Hermann Brenner
- Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), 69120 Heidelberg, Germany
- German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Correspondence: ; Tel.: +49-6221-421300; Fax: +49-6221-421302
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Fellizar A, Refuerzo V, Ramos JD, Albano PM. Expression of specific microRNAs in tissue and plasma in colorectal cancer. J Pathol Transl Med 2022; 57:147-157. [PMID: 35501673 DOI: 10.4132/jptm.2022.02.19] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2021] [Accepted: 02/19/2022] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND MicroRNAs (miRNA/miR) play significant roles in the regulation of cell differentiation, cell cycle progression, and apoptosis. They become dysregulated during carcinogenesis and are eventually released into the circulation, enabling their detection in body fluids. Thus, this study compared the miRNA expression in tissue and plasma samples of colorectal cancer (CRC) patients and clinically healthy controls and determined miRNA expression as a potential CRC biomarker. METHODS Using quantitative reverse transcription polymerase chain reaction (RT-qPCR), miR-21-5p, miR-29a-3p, miR-92a-3p, miR-135b-5p, miR-196b-5p, and miR-197-3p, expression was analyzed and compared between the malignant (n = 41) and the adjacent neoplasm free mucosal tissues (n = 41) of CRC patients. The findings were validated in plasma samples (n = 36) collected from the same CRC patients prior to surgery or any form of treatment and compared to plasma from their age and sex-matched controls (n = 36). RESULTS MiR-21-5p, miR-29a-3p, miR-92a-3p, and miR- 196b-5p were upregulated and miR-135b-5p was downregulated in CRC malignant tissues compared to their expression in adjacent neoplasm-free tissue. This was further observed in the plasma of the same CRC cases compared to controls. MiR-92a-3p showed itself the most sensitive (0.93; p < .001) and most specific (0.95; p < .001) in detecting CRC in tissue. In plasma, miR-196b-5p was the most sensitive (0.97; p < .001) and specific (0.94; p < .001) in detecting CRC. Plasma miR-92a-3p and miR-196b-5p were the most sensitive (0.95; p < .001) and specific (0.94; p < .001) in the early detection of CRC. CONCLUSIONS Results show that specific miRNAs dysregulated in malignant tissues are released and can be detected in the circulation, supporting their potential as non-invasive biomarkers of CRC.
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Hajibabaie F, Abedpoor N, Assareh N, Tabatabaiefar MA, Shariati L, Zarrabi A. The Importance of SNPs at miRNA Binding Sites as Biomarkers of Gastric and Colorectal Cancers: A Systematic Review. J Pers Med 2022; 12:jpm12030456. [PMID: 35330456 PMCID: PMC8954022 DOI: 10.3390/jpm12030456] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 03/08/2022] [Accepted: 03/09/2022] [Indexed: 02/04/2023] Open
Abstract
Dysregulated mRNA–miRNA profiles might have the prospective to be used for early diagnosis of gastrointestinal cancers, estimating survival, and predicting response to treatment. Here, a novel biomarker based on miRNAs binding to mRNAs in single nucleotide polymorphism (SNP) sites related to gastrointestinal cancers is introduced that could act as an early diagnosis. The electronic databases used for the recruiting published articles included EMBASE, SCOPUS, Web of Science, and PubMed, based on MESH keywords and PRISMA methodology. Based on the considered criteria, different experimental articles were reviewed, during which 15 studies with the desired criteria were collected. Accordingly, novel biomarkers in prediction, early prognosis, and diagnosis of gastrointestinal cancers were highlighted. Moreover, it was found that 20 SNP sites and 16 miRNAs were involved in gastrointestinal cancers, with altered expression patterns associated with clinicopathological and demographic data. The results of this systematic study revealed that SNPs could affect the binding of miRNAs in the SNP sites that might play a principal role in the progression, invasion, and susceptibility of gastrointestinal cancers. In addition, it was found that the profiles of SNPs and miRNAs could serve as a convenient approach for the prognosis and diagnosis of gastric and colorectal cancers.
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Affiliation(s)
- Fatemeh Hajibabaie
- Department of Physiology, Medicinal Plants Research Center, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan 81595-158, Iran; (F.H.); (N.A.)
| | - Navid Abedpoor
- Department of Sports Physiology, Faculty of Sports Sciences, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan 81595-158, Iran;
| | - Nazanin Assareh
- Department of Physiology, Medicinal Plants Research Center, Isfahan (Khorasgan) Branch, Islamic Azad University, Isfahan 81595-158, Iran; (F.H.); (N.A.)
| | - Mohammad Amin Tabatabaiefar
- Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran;
- Pediatric Inherited Diseases Research Center, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
| | - Laleh Shariati
- Department of Biomaterials, Nanotechnology and Tissue Engineering, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
- Biosensor Research Center, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
- Correspondence: (L.S.); (A.Z.)
| | - Ali Zarrabi
- Biomedical Engineering Department, Faculty of Engineering and Natural Sciences, Istinye University, Sariye, Istanbul 34396, Turkey
- Correspondence: (L.S.); (A.Z.)
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Ghosh A, Ranjan N, Jiang L, Ansari AH, Degyatoreva N, Ahluwalia S, Arya DP, Maiti S. Fine-tuning miR-21 expression and inhibition of EMT in breast cancer cells using aromatic-neomycin derivatives. MOLECULAR THERAPY. NUCLEIC ACIDS 2022; 27:685-698. [PMID: 35070496 PMCID: PMC8763640 DOI: 10.1016/j.omtn.2021.12.027] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 12/17/2021] [Indexed: 12/14/2022]
Abstract
MicroRNAs (miRs) are a class of endogenously expressed non-coding RNAs that negatively regulate gene expression within cells and participate in maintaining cellular homeostasis. By targeting 3' UTRs of target genes, individual miRs can control a wide array of gene expressions. Previous research has shed light upon the fact that aberrantly expressed miRs within cells can pertain to diseased conditions, such as cancer. Malignancies caused due to miRs are because of the high expression of onco-miRs or feeble expression of tumor-suppressing miRs. Studies have also shown miRs to engage in epithelial to mesenchymal transition (EMT), which allows cancer cells to become more invasive and metastasize. miR-21 is an onco-miR highly expressed in breast cancer cells and targets protein PTEN, which abrogates EMT. Therefore, we discuss an approach where in-house-developed peptidic amino sugar molecules have been used to target pre-miR-21 to inhibit miR-21 biogenesis, and hence antagonize its tumor-causing effect and inhibit EMT. Our study shows that small-molecule-based fine-tuning of miR expression can cause genotypic as well as phenotypic changes and also reinstates the potential and importance of nucleic acid therapeutics.
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Affiliation(s)
- Arpita Ghosh
- CSIR-Institute of Genomics & Integrative Biology, Mathura Road, Delhi 110025, India.,Academy of Scientific & Innovative Research, CSIR- Human Resource Development Centre (CSIR-HRDC) Campus, Sector 19, Kamla Nehru Nagar, Ghaziabad 201 002, Uttar Pradesh, India
| | - Nihar Ranjan
- Department of Chemistry, Clemson University, Clemson, SC 29634, USA
| | - Liuwei Jiang
- Department of Chemistry, Clemson University, Clemson, SC 29634, USA
| | - Asgar Hussain Ansari
- CSIR-Institute of Genomics & Integrative Biology, Mathura Road, Delhi 110025, India.,Academy of Scientific & Innovative Research, CSIR- Human Resource Development Centre (CSIR-HRDC) Campus, Sector 19, Kamla Nehru Nagar, Ghaziabad 201 002, Uttar Pradesh, India
| | | | - Shivaksh Ahluwalia
- CSIR-Institute of Genomics & Integrative Biology, Mathura Road, Delhi 110025, India.,Kusuma School of Biological Sciences, Indian Institute of Technology Delhi, New Delhi, Delhi 110016, India
| | - Dev P Arya
- Department of Chemistry, Clemson University, Clemson, SC 29634, USA.,NUBAD LLC, Greenville, SC 29605, USA
| | - Souvik Maiti
- CSIR-Institute of Genomics & Integrative Biology, Mathura Road, Delhi 110025, India.,Academy of Scientific & Innovative Research, CSIR- Human Resource Development Centre (CSIR-HRDC) Campus, Sector 19, Kamla Nehru Nagar, Ghaziabad 201 002, Uttar Pradesh, India
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Mahmoud HA, El Amin HA, Ahmed ESM, Kenawy AG, El-Ebidi AM, ElNakeeb I, Kholef EFM, Elsewify WAE. Role of MicroRNA-223 and MicroRNA-182 as Novel Biomarkers in Early Detection of Colorectal Cancer. Int J Gen Med 2022; 15:3281-3291. [PMID: 35368799 PMCID: PMC8964337 DOI: 10.2147/ijgm.s353244] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2021] [Accepted: 03/10/2022] [Indexed: 12/18/2022] Open
Abstract
Background Colorectal cancer is a common and lethal disease. It is estimated that approximately 145,600 new cases of large bowel cancer are diagnosed annually in the USA. MiRNA-223 and miRNA-182 have been reported in various cancers, such as lung, gastric, breast and colorectal cancer and proposed to be valid and reliable for diagnosis as well as prognosis. Aim This study aimed to determine the role of miR-223 and miR-182 as novel biomarkers for early detection and prognosis of CRC. Patient and Methods This case–control study was conducted at the department of Internal Medicine, Aswan University Hospital, in the period from the 1st of February 2020 to the 20th of April 2021. Thirty-five cases and thirty age- and sex-matched controls were included in the study. All patients were subject to complete clinical evaluation, routine investigations, occult blood in stool, serum levels of CEA and CA 19–9, serum levels of miR-223 and miR-182 by quantitative PCR. Results Significant difference between the two studied groups regarding biomarker changes was found. ROC curve analysis showed that the new markers had excellent diagnostic as well as prognostic criteria. Micro-RNA-223 diagnostic accuracy, sensitivity, specificity, PPV, NPV, FDR and FOR were 97%, 97.1%, 96.7%, 97%, 97%, 3.3% and 2.9%, respectively. Also, micro-RNA-182 diagnostic accuracy, sensitivity, specificity, PPV, NPV, FDR and FOR were 97%, 98%, 96%, 96%, 98%, 3.9% and 2%, respectively. Conclusion MiR-223 and miR-182 have been discovered to be relevant and reliable biomarkers for the early identification and prognosis of CRC. Increased levels of miR-223 and miR-182 were associated with increased risk of disease progression, and the more accurate the value of miR-223 and miR-182, the earlier the diagnosis of colorectal cancer.
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Affiliation(s)
- Hala A Mahmoud
- Department of Internal Medicine, Faculty of Medicine, Aswan University, Aswan, Egypt
| | - Hussein Ahmed El Amin
- Department of Internal Medicine, Faculty of Medicine, Assiut University, Assiut, Egypt
| | | | - Ahmed Gaber Kenawy
- Department of Internal Medicine, Faculty of Medicine, Aswan University, Aswan, Egypt
| | - Abdallah M El-Ebidi
- Department of Biochemistry, Faculty of Medicine, Aswan University, Aswan, Egypt
| | - Islam ElNakeeb
- Department of Clinical Pathology, Faculty of Medicine, Aswan University, Aswan, Egypt
| | | | - Wael Abd Elgwad Elsewify
- Department of Internal Medicine, Faculty of Medicine, Aswan University, Aswan, Egypt
- Correspondence: Wael Abd Elgwad Elsewify, Department of Internal Medicine, Faculty of Medicine, Aswan University, Aswan, 81528, Egypt, Tel +201001657295, Fax +20973480449, Email
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CD44 Expression Intensity Marks Colorectal Cancer Cell Subpopulations with Different Extracellular Vesicle Release Capacity. Int J Mol Sci 2022; 23:ijms23042180. [PMID: 35216292 PMCID: PMC8879498 DOI: 10.3390/ijms23042180] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/18/2022] [Revised: 02/11/2022] [Accepted: 02/14/2022] [Indexed: 02/04/2023] Open
Abstract
Extracellular vesicles (EV) are released by virtually all cells and they transport biologically important molecules from the release site to target cells. Colorectal cancer (CRC) is a leading cause of cancer-related death cases, thus, it represents a major health issue. Although the EV cargo may reflect the molecular composition of the releasing cells and thus, EVs may hold a great promise for tumor diagnostics, the impact of intratumoral heterogeneity on the intensity of EV release is still largely unknown. By using CRC patient-derived organoids that maintain the cellular and molecular heterogeneity of the original epithelial tumor tissue, we proved that CD44high cells produce more organoids with a higher proliferation intensity, as compared to CD44low cells. Interestingly, we detected an increased EV release by CD44high CRC cells. In addition, we found that the miRNA cargos of CD44high and CD44low cell derived EVs largely overlapped and only four miRNAs were specific for one of the above subpopulations. We observed that EVs released by CD44high cells induced the proliferation and activation of colon fibroblasts more strongly than CD44low cells. However, this effect was due to the higher EV number rather than to the miRNA cargo of EVs. Collectively, we identified CRC subpopulations with different EV releasing capabilities and we proved that CRC cell-released EVs have a miRNA-independent effect on fibroblast proliferation and activation.
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miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR. Int J Mol Sci 2022; 23:ijms23042107. [PMID: 35216222 PMCID: PMC8876010 DOI: 10.3390/ijms23042107] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2021] [Revised: 01/26/2022] [Accepted: 02/10/2022] [Indexed: 12/24/2022] Open
Abstract
Regulatory changes occurring early in colorectal cancer development remain poorly investigated. Since the majority of cases develop from polyps in the adenoma-carcinoma transition, a search of early molecular features, such as aberrations in miRNA expression occurring prior to cancer development, would enable identification of potentially causal, rather than consequential, candidates in the progression of polyp to cancer. In the current study, by employing small RNA-seq profiling of colon biopsy samples, we described differentially expressed miRNAs and their isoforms in the adenoma-carcinoma transition. Analysis of healthy-adenoma-carcinoma sequence in an independent validation group enabled us to identify early deregulated miRNAs including hsa-miR-1246 and hsa-miR-215-5p, the expressions of which are, respectively, gradually increasing and decreasing. Loss-of-function experiments revealed that inhibition of hsa-miR-1246 lead to reduced cell viability, colony formation, and migration rate, thereby indicating an oncogenic effect of this miRNA in vitro. Subsequent western blot and luciferase reporter assay provided evidence of hsa-miR-1246 being involved in the regulation of target AXIN2 and CFTR genes’ expression. To conclude, the present study revealed possible involvement of hsa-miR-1246 in early colorectal cancer development and regulation of tumor suppressors AXIN2 and CFTR.
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Novel Diagnostic Biomarkers in Colorectal Cancer. Int J Mol Sci 2022; 23:ijms23020852. [PMID: 35055034 PMCID: PMC8776048 DOI: 10.3390/ijms23020852] [Citation(s) in RCA: 99] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2021] [Revised: 12/27/2021] [Accepted: 01/03/2022] [Indexed: 02/06/2023] Open
Abstract
Colorectal cancer (CRC) is still a leading cause of cancer death worldwide. Less than half of cases are diagnosed when the cancer is locally advanced. CRC is a heterogenous disease associated with a number of genetic or somatic mutations. Diagnostic markers are used for risk stratification and early detection, which might prolong overall survival. Nowadays, the widespread use of semi-invasive endoscopic methods and feacal blood tests characterised by suboptimal accuracy of diagnostic results has led to the detection of cases at later stages. New molecular noninvasive tests based on the detection of CRC alterations seem to be more sensitive and specific then the current methods. Therefore, research aiming at identifying molecular markers, such as DNA, RNA and proteins, would improve survival rates and contribute to the development of personalized medicine. The identification of “ideal” diagnostic biomarkers, having high sensitivity and specificity, being safe, cheap and easy to measure, remains a challenge. The purpose of this review is to discuss recent advances in novel diagnostic biomarkers for tumor tissue, blood and stool samples in CRC patients.
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Adams E, Sepich-Poore GD, Miller-Montgomery S, Knight R. Using All Our Genomes: Blood-based Liquid Biopsies for the Early Detection of Cancer. VIEW 2022; 3:20200118. [PMID: 35872970 PMCID: PMC9307139 DOI: 10.1002/viw.20200118] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2021] [Accepted: 10/22/2021] [Indexed: 02/02/2023] Open
Abstract
The pursuit of highly sensitive and specific cancer diagnostics based on cell-free (cf) nucleic acids isolated from minimally invasive liquid biopsies has been an area of intense research and commercial effort for at least two decades. Most of these tests detect cancer-specific mutations or epigenetic modifications on circulating DNA derived from tumor cells (ctDNA). Although recent FDA approvals of both single and multi-analyte liquid biopsy companion diagnostic assays are proof of the tremendous progress made in this domain, using ctDNA for the diagnosis of early-stage (stage I/II) cancers remains challenging due to several factors, such as low mutational allele frequency in circulation, overlapping profiles in genomic alterations among diverse cancers, and clonal hematopoiesis. This review discusses these analytical challenges, interim solutions, and the opportunity to complement ctDNA diagnostics with microbiome-aware analyses that may mitigate several existing ctDNA assay limitations.
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Affiliation(s)
| | - Gregory D Sepich-Poore
- Micronoma, Inc., San Diego, CA, USA
- Department of Bioengineering, University of California San Diego, La Jolla, CA, USA
| | | | - Rob Knight
- Department of Bioengineering, University of California San Diego, La Jolla, CA, USA
- Department of Pediatrics, University of California San Diego, La Jolla, CA, USA
- Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
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Kao WY, Yang CL, Tsai FM, Chen CW, Hsiao KH, Chen JH. Comparing miR-16 and miR-1228 as an optimal endogenous control for quantification of circulating microRNAs in colorectal cancer patients. Tzu Chi Med J 2022; 34:318-322. [PMID: 35912051 PMCID: PMC9333100 DOI: 10.4103/tcmj.tcmj_240_21] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2021] [Revised: 09/08/2021] [Accepted: 12/20/2021] [Indexed: 11/06/2022] Open
Abstract
Objectives: Circulating microRNAs (miRNAs) have been discovered to play a novel role in intercellular communication and cancer biology. They are emerging candidates for noninvasive molecular biomarkers of cancer and other diseases. However, current translational researches have been limited by the lack of consensus on the optimal endogenous control of circulating miRNAs quantitation. In this study, we compared two promising miRNAs, miR-1228 and miR-16, as an endogenous control. The effects of normalizers on the relative quantification of circulating miR-31 in plasma samples of colorectal cancer (CRC) were also assessed. Materials and Methods: The cel-miR-39 was a spiked-in RNA used as an external control and added to plasma samples before RNA extraction. Quantitative real-time polymerase chain reaction technology was used to analyze the expression levels of circulating miRNAs in plasma samples of 4 healthy controls and 14 CRC patients. The expression stability of the candidate controls was compared by Ct analysis and NormFinder algorithms. Results: There was no significant difference in expression level of miR-16 and miR-1228 between healthy control group and before or after therapy of CRC patient groups. The expression of miR-1228 has smaller the range Ct values (28.25-25.64)compared with those of miR-16 (24.91-20.34). The stability value of miR-1228 (0.102) is lower than that of miR-16 (0.350). The expression of miR-1228 endogenous reference candidate has lower stability value and smaller the range Ct values compared with those in miR-16. According to the range Ct values and stability value, miR-1228 is better than miR-16 as endogenous control in CRC patients. There are significant differences in circulating miR-31 expression between healthy control and CRC patients when miR-1228 was used to standardize miR-31 expression. Conclusions: miR-1228 is recommended as a better endogenous control in quantification of circulating miRNAs in CRC patients.
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Soremekun O, Ezenwa C, Paimo O, Madu C, Omotoso O, Akinifesi O, Ntuenibok N. Integrative analysis of microRNA expression level profile identifies microRNAs associated with prostate cancer. GENE REPORTS 2021. [DOI: 10.1016/j.genrep.2021.101376] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
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