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Yu J, Shen Y, Xu Y, Feng Z, Shen Y, Zhu Y, Huan J, Peng Q. MicroRNA-486: a dual-function biomarker for diagnosis and tumor immune microenvironment characterization in non-small cell lung cancer. BMC Med Genomics 2025; 18:92. [PMID: 40390034 PMCID: PMC12090393 DOI: 10.1186/s12920-025-02158-9] [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: 03/25/2025] [Accepted: 05/07/2025] [Indexed: 05/21/2025] Open
Abstract
BACKGROUND This investigation evaluates the clinical significance and molecular mechanisms of microRNA-486 (miR-486) as a potential biomarker in non-small cell lung cancer (NSCLC) through an integrative analytical approach. METHODS We conducted systematic search and meta-analysis of diagnostic studies from major biomedical databases from inception through April 04, 2025, followed by comprehensive bioinformatics interrogation. Protein-protein interaction (PPI) networks were constructed using STRING to identify key hub genes regulated by miR-486. Validation of hub genes employed TCGA datasets, while immune infiltration analysis utilized TIMER2.0 platform. RESULTS The meta-analysis indicated that miR-486, both individually and in combination, could be effective biomarkers for NSCLC detection. Afterwards, functional enrichment analyses of miR-486 target genes highlighted significant ontology terms and pathways crucial to the initiation and progression of NSCLC. PPI networks revealed key proteins and modules that participate in multiple essential pathways associated with NSCLC pathogenesis. Furthermore, the identified hub genes were validated for differential expression in cancerous versus normal tissues, suggesting their potential diagnostic utility, while subsequent survival analyses confirmed their prognostic value through significant associations with overall survival. Notably, these hub genes were found to be significantly associated with immune infiltration levels, immune microenvironment scores, and immune-related proteins in NSCLC. CONCLUSIONS This dual-modality investigation establishes miR-486 as a multi-functional biomarker in NSCLC, demonstrating both diagnostic utility and immunoregulatory potential through tumor microenvironment modulation.
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Affiliation(s)
- Jun Yu
- Department of Medical Engineering, Wuxi No.2 People's Hospital, Wuxi, China
| | - Yi Shen
- Department of Radiation Oncology, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China
| | - Yao Xu
- Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Zhengyang Feng
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yuntian Shen
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Jiangsu, Suzhou, 215004, China
| | - Yaqun Zhu
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Jiangsu, Suzhou, 215004, China
| | - Jian Huan
- Department of Radiation Oncology, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China
| | - Qiliang Peng
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Jiangsu, Suzhou, 215004, China.
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Peng Q, Shen Y, Xu Y, Feng Z, Xu Y, Wang Y, Zou L, Zhu Y, Shen Y. Association of metabolic dysregulation with treatment response in rectal cancer patients undergoing chemoradiotherapy. BMC Med Genomics 2025; 18:48. [PMID: 40075399 PMCID: PMC11905535 DOI: 10.1186/s12920-025-02114-7] [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: 11/08/2024] [Accepted: 02/25/2025] [Indexed: 03/14/2025] Open
Abstract
BACKGROUND This study aimed to explore the metabolic changes during neoadjuvant chemoradiotherapy (NCRT) in patients with locally advanced rectal cancer (LARC) by serum metabolomics analysis, and to provide new biomarkers for individualized treatment and efficacy prediction. METHODS Serum samples from 20 patients with LARC before, during and after NCRT were collected for metabolomic analysis. The metabolites in the serum samples were analyzed qualitatively and quantitatively using gas chromatography-mass spectrometry (GC-MS). Meanwhile, the differences in metabolic profiles at different time points were compared and significantly changed metabolites were screened. RESULTS The metabolic profiles of patients were significantly altered at different time points of NCRT. Through metabolomic analysis, we identified metabolites that were significantly altered during NCRT and revealed alterations in the associated metabolic pathways. The predictive power of pre-radiotherapy isocitric acid and pro-radiotherapy 3-hydroxy-3-(4'-hydroxy-3'-methoxyphenyl) propionic acid in distinguishing patients sensitive and non-sensitive to NCRT was markedly high, with AUC values of 0.875 and 0.75, respectively. Additional analysis indicated that a combined panel of serum metabolites yielded even higher AUC values, thereby enhancing the accuracy of predicting the efficacy of neoadjuvant NCRT. CONCLUSION This study revealed metabolic changes and corresponding alterations in metabolic pathways during NCRT in patients with LARC by serum metabolomic analysis. The metabolic disorders may be associated with poor outcomes in patients treated with NCRT for rectal cancer, providing new biomarkers for individualized treatment and prognostic assessment. Further studies and validation will help to gain insight into the mechanism of these metabolic changes and provide more basis for clinical application.
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Affiliation(s)
- Qiliang Peng
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
- State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Yi Shen
- Department of Radiation Oncology, Suzhou Research Center of Medical School, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China
| | - Yingying Xu
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Zhengyang Feng
- State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yao Xu
- Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yong Wang
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Li Zou
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Yaqun Zhu
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China.
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China.
| | - Yuntian Shen
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, Jiangsu, 215004, China.
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China.
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Yamamoto-Furusho JK, Gutierrez-Herrera FD. Molecular Mechanisms and Clinical Aspects of Colitis-Associated Cancer in Ulcerative Colitis. Cells 2025; 14:162. [PMID: 39936954 PMCID: PMC11817687 DOI: 10.3390/cells14030162] [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: 11/28/2024] [Revised: 01/14/2025] [Accepted: 01/20/2025] [Indexed: 02/13/2025] Open
Abstract
Inflammatory bowel diseases have long been recognized as entities with a higher risk of colorectal cancer. An increasing amount of information has been published regarding ulcerative colitis-associated colorectal cancer and its unique mechanisms in recent decades, as ulcerative colitis constitutes a chronic process characterized by cycles of activity and remission of unpredictable durations and intensities; cumulative genomic alterations occur during active disease and mucosal healing, resulting in a special sequence of events different to the events associated with sporadic colorectal cancer. The recognition of the core differences between sporadic colorectal cancer and colitis-associated cancer is of great importance to understand and guide the directions in which new research could be performed, and how it could be applied to current clinical scenarios. A DSS/AOM murine model has allowed for a better understanding of the pathogenic mechanisms in colitis-associated cancer, as it is currently the closest model to this unique scenario. In this review, we provide a summary of the main molecular mechanisms and the clinical aspects of colitis-associated cancer in ulcerative colitis.
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Affiliation(s)
- Jesus K. Yamamoto-Furusho
- Inflammatory Bowel Disease Clinic, Department of Gastroenterology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Ciudad de México 14080, Mexico;
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Peng Q, Jiang L, Shen Y, Xu Y, Shen X, Zou L, Zhu Y, Shen Y. LC-MS metabolomics analysis of serum metabolites during neoadjuvant chemoradiotherapy in locally advanced rectal cancer. Clin Transl Oncol 2024; 26:3150-3168. [PMID: 38831193 DOI: 10.1007/s12094-024-03537-x] [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: 04/24/2024] [Accepted: 05/18/2024] [Indexed: 06/05/2024]
Abstract
BACKGROUND This study aimed to investigate the serum metabolite profiles during neoadjuvant chemoradiotherapy (NCRT) in locally advanced rectal cancer (LARC) using liquid chromatography-mass spectrometry (LC-MS) metabolomics analysis. METHODS 60 serum samples were collected from 20 patients with LARC before, during, and after radiotherapy. LC-MS metabolomics analysis was performed to identify the metabolite variations. Functional annotation was applied to discover altered metabolic pathways. The key metabolites were screened and their ability to predict sensitivity to radiotherapy was calculated using random forests and ROC curves. RESULTS The results showed that NCRT led to significant changes in the serum metabolite profiles. The serum metabolic profiles showed an apparent separation between different time points and different sensitivity groups. Moreover, the functional annotation showed that the differential metabolites were associated with a series of important metabolic pathways. Pre-radiotherapy (3Z,6Z)-3,6-Nonadiena and pro-radiotherapy 1-Hydroxyibuprofen showed good predictive performance in discriminating the sensitive and non-sensitive group to NCRT, with an AUC of 0.812 and 0.75, respectively. Importantly, the combination of different metabolites significantly increased the predictive ability. CONCLUSION This study demonstrated the potential of LC-MS metabolomics for revealing the serum metabolite profiles during NCRT in LARC. The identified metabolites may serve as potential biomarkers and therapeutic targets for the management of this disease. Furthermore, the understanding of the affected metabolic pathways may help design more personalized therapeutic strategies for LARC patients.
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Affiliation(s)
- Qiliang Peng
- Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
- State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Lili Jiang
- Department of Oncology, Nantong Haimen District People's Hospital, Jiangsu, China
| | - Yi Shen
- Department of Radiation Oncology, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China
| | - Yao Xu
- Department of Radiology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Xinan Shen
- Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Li Zou
- Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Yaqun Zhu
- Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China.
| | - Yuntian Shen
- Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China.
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Jeo WS, Lalisang TJM, Siregar NC, Sudoyo AW, Pakasi T, Jusman SW, Asmarinah A. Semiquantitative assessment of phosphatase and tensin homolog value with immunohistochemistry in colorectal cancer. Int J Biol Markers 2024; 39:248-254. [PMID: 39118563 DOI: 10.1177/03936155241265346] [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] [Indexed: 08/10/2024]
Abstract
INTRODUCTION Colorectal cancer has emerged as a concerning health problem, ranking the third most common form of cancer in both men and women. The phosphatase and tensin homologue (PTEN) protein is widely known for its role as an inhibitor of the phosphatidylinositol 3-kinase/protein kinase-B/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway, playing a major role inhibiting tumor development. Previous studies investigated the role of this protein in the PI3K pathway and how it affected colorectal cancer. However, a standardized cut-off value for PTEN expression has not been established. METHODS Immunohistochemistry was used in examining PTEN. The staining grade ranging from 0 to 3 was then multiplied by the number of 100 cancer cells counted, with total score between 0 and 300. In this study, receiver operating characteristic (ROC) curve was employed to determine the expression cut-off value for PTEN in colorectal cancer. RESULTS This study showed statistically significant results (P < 0.001) in either tumor or non-tumor tissues by using the ROC curve with a cut-off value of 199.0. This study also revealed significant correlation between nodal status with PTEN (P = 0.008) and stage with PTEN (P = 0.019) with sensitivity 0.753 and specificity 0.728. CONCLUSION Semiquantitative assessment with cell counting multiplied by color intensity is a good method in determining PTEN expression. The use of immunohistochemical staining intensity and cell scoring with ROC cut-off is effective to elaborate the effects of PTEN in colorectal cancer (PTEN value > 199.0 was classified as strong and ≤ 199.0 as weak).
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Affiliation(s)
- Wifanto S Jeo
- Department of Surgery, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Toar J M Lalisang
- Department of Surgery, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Nurjati C Siregar
- Department of Pathology Anatomy, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Aru W Sudoyo
- Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Trevino Pakasi
- Department of Primary Medicine, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Sri W Jusman
- Department of Biochemistry, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
| | - Asmarinah Asmarinah
- Department of Biology, Faculty of Medicine, University of Indonesia, Jakarta, Indonesia
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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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Heidarian S, Takbiri Osgoei L, Zare Karizi S, Amani J, Arbabian S. Signal-On Fluorescence Biosensor for Detection of miRNA-21 Based on ROX labeled Specific Stem-Loop Probe. IRANIAN JOURNAL OF PHARMACEUTICAL RESEARCH : IJPR 2024; 23:e144368. [PMID: 39005737 PMCID: PMC11246647 DOI: 10.5812/ijpr-144368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/06/2024] [Revised: 02/21/2024] [Accepted: 02/26/2024] [Indexed: 07/16/2024]
Abstract
Background The abnormal expression of microRNA (miRNA) influences RNA transcription and protein translation, leading to tumor progression and metastasis. Today, reliably identifying aberrant miRNA expression remains challenging, especially when employing quick, simple, and portable detection methods. Objectives This study aimed to diagnose and detect the miR-21 biomarker with high sensitivity and specificity. Methods Our detection approach involves immobilizing ROX dye-labeled single-stranded DNA probes (ROX-labeled ssDNA) onto MWCNTs to detect target miRNA-21. Initially, adsorbing ROX-labeled ssDNA onto MWCNTs causes fluorescence quenching of ROX. Subsequently, introducing its complementary DNA (cDNA) forms double-stranded DNA (dsDNA), which results in the desorption and release from MWCNTs, thus restoring ROX fluorescence. Results The study examined changes in fluorescence intensities before and after hybridization with miRNA-21. The fluorescence emission intensities responded linearly to increases in miR-21 concentration from 10-9 to 3.2 × 10-6 M. The developed fluorescence sensor exhibited a detection limit of 1.12 × 10-9 M. Conclusions This work demonstrates that using a nano-biosensor based on carbon nanotubes offers a highly sensitive method for the early detection of colorectal cancer (CRC), supplementing existing techniques.
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Affiliation(s)
- Somayeh Heidarian
- Department of Biology, Faculty of Biological Science, North Tehran Branch, Islamic Azad University, Tehran, Iran
| | - Laya Takbiri Osgoei
- Department of Microbiology, Faculty of Biological Science, North Tehran Branch. Islamic Azad University, Tehran, Iran
| | - Shohreh Zare Karizi
- Department of Biology, Varamin Pishva, Branch, Islamic Azad University Pishva, Varamin, Iran
| | - Jafar Amani
- Microbiology Research Center, Systems Biology and Poisonings Institute, Baqiyatallah University of Medical Sciences, Tehran, Iran
| | - Sedigheh Arbabian
- Department of Biology, Faculty of Biological Science, North Tehran Branch, Islamic Azad University, Tehran, Iran
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Hanusova V, Matouskova P, Manethova M, Soukup J, John S, Zofka M, Vošmikova H, Krbal L, Rudolf E. Comparative Analysis of miRNA and EMT Markers in Metastatic Colorectal Cancer. Cancer Invest 2023; 41:837-847. [PMID: 37997798 DOI: 10.1080/07357907.2023.2283495] [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: 12/14/2020] [Accepted: 11/09/2023] [Indexed: 11/25/2023]
Abstract
Colorectal cancer (CRC) is the fourth most commonly diagnosed malignant condition in the world. Micro RNAs (miRNAs) as well as epithelial to mesenchymal transition (EMT) play an important role in the pathogenesis of CRC. We performed a comparative analysis of the expression of selected miRNA genes and EMT markers in bioptic samples from patients (n = 45) with primary CRC or metastatic (m)CRC to the regional lymph node using reverse transcription-quantitative PCR and IHC staining. Results: Out of all miRNA analyzed, the miR-17 expression was most significantly different and associated with lower risk of CRC spread to the lymph node. In addition, significant relationships were found between the tumor side localization and several miRNAs expressions (miR-9, miR-29b, miR-19a, miR-19b, miR-21, miR-106a, miR-20a and miR-17). In addition, of the examined EMT markers, only VEGFA expression correlated with tumor progression (tumor grade G2). In the examined set of patient samples and their matched healthy tissue, several specific molecular markers (miRNAs associated with EMT and tumor progression) were identified with a promising prognostic potential. Their further examination in larger patient cohorts is planned to validate the present data.
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Affiliation(s)
- Veronika Hanusova
- Department of Medical Biology and Genetics, Faculty of Medicine, Charles University, Czech Republic
| | - Petra Matouskova
- Department of Biochemistry, Faculty of Pharmacy, Charles University, Czech Republic
| | - Monika Manethova
- The Fingerland Department of Pathology, Faculty of Medicine and University Hospital in Hradec Kralove, Charles University, Czech Republic
| | - Jiri Soukup
- The Fingerland Department of Pathology, Faculty of Medicine and University Hospital in Hradec Kralove, Charles University, Czech Republic
| | - Stanislav John
- Department of Medical Biology and Genetics, Faculty of Medicine, Charles University, Czech Republic
- The Department of Oncology and Radiotherapy, Faculty of Medicine and University Hospital in Hradec Kralove, Charles University, Czech Republic
| | - Martin Zofka
- Department of Biochemistry, Faculty of Pharmacy, Charles University, Czech Republic
| | - Hana Vošmikova
- The Fingerland Department of Pathology, Faculty of Medicine and University Hospital in Hradec Kralove, Charles University, Czech Republic
| | - Lukas Krbal
- The Fingerland Department of Pathology, Faculty of Medicine and University Hospital in Hradec Kralove, Charles University, Czech Republic
| | - Emil Rudolf
- Department of Medical Biology and Genetics, Faculty of Medicine, Charles University, Czech Republic
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Peng Q, Ren B, Xin K, Liu W, Alam MS, Yang Y, Gu X, Zhu Y, Tian Y. CYFIP2 serves as a prognostic biomarker and correlates with tumor immune microenvironment in human cancers. Eur J Med Res 2023; 28:364. [PMID: 37735711 PMCID: PMC10515071 DOI: 10.1186/s40001-023-01366-2] [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: 07/11/2023] [Accepted: 09/12/2023] [Indexed: 09/23/2023] Open
Abstract
BACKGROUND The mechanisms whereby CYFIP2 acts in tumor development and drives immune infiltration have been poorly explored. Thus, this study aimed to identifying the role of CYFIP2 in tumors and immune response. METHODS In this study, we first explored expression patterns, diagnostic role and prognostic value of CYFIP2 in cancers, particularly in lung adenocarcinoma (LUAD). Then, we performed functional enrichment, genetic alterations, DNA methylation analysis, and immune cell infiltration analysis of CYFIP2 to uncover its potential mechanisms involved in immune microenvironment. RESULTS We found that CYFIP2 significantly differentially expressed in different tumors including LUAD compared with normal tissues. Furthermore, CYFIP2 was found to be significantly correlated with clinical parameters in LUAD. According to the diagnostic and survival analysis, CYFIP2 may be employed as a potential diagnostic and prognostic biomarker. Moreover, genetic alterations revealed that mutation of CYFIP2 was the main types of alterations in different cancers. DNA methylation analysis indicated that CYFIP2 mRNA expression correlated with hypomethylation. Afterwards, functional enrichment analysis uncovered that CYFIP2 was involved in tumor-associated and immune-related pathways. Immune infiltration analysis indicated that CYFIP2 was significantly correlated with immune cells infiltration. In particular, CYFIP2 was strongly linked with immune microenvironment scores. Additionally, CYFIP2 exhibited a significant relationship with immune regulators and immune-related genes including chemokines, chemokines receptors, and MHC genes. CONCLUSION Our results suggested that CYFIP2 may serve as a prognostic cancer biomarker for determining prognosis and might be a promising therapeutic strategy for tumor immunotherapy.
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Affiliation(s)
- Qiliang Peng
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, 215004, Jiangsu, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
- State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Bixin Ren
- Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Kedao Xin
- Department of Radiation Oncology, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China
| | - Weihui Liu
- Department of Oncology, Dazhou Central Hospital, Dazhou, China
| | - Md Shahin Alam
- Laboratory of Molecular Neuropathology, Department of Pharmacology, Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences, Soochow University, Suzhou, China
| | - Yinyin Yang
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, 215004, Jiangsu, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Xuhao Gu
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, 215004, Jiangsu, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Yaqun Zhu
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, 215004, Jiangsu, China.
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China.
- State Key Laboratory of Radiation Medicine and Protection, Soochow University, Suzhou, China.
| | - Ye Tian
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, San Xiang Road No. 1055, Suzhou, 215004, Jiangsu, China.
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China.
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Kasprzak A. Prognostic Biomarkers of Cell Proliferation in Colorectal Cancer (CRC): From Immunohistochemistry to Molecular Biology Techniques. Cancers (Basel) 2023; 15:4570. [PMID: 37760539 PMCID: PMC10526446 DOI: 10.3390/cancers15184570] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Revised: 09/04/2023] [Accepted: 09/13/2023] [Indexed: 09/29/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common and severe malignancies worldwide. Recent advances in diagnostic methods allow for more accurate identification and detection of several molecular biomarkers associated with this cancer. Nonetheless, non-invasive and effective prognostic and predictive testing in CRC patients remains challenging. Classical prognostic genetic markers comprise mutations in several genes (e.g., APC, KRAS/BRAF, TGF-β, and TP53). Furthermore, CIN and MSI serve as chromosomal markers, while epigenetic markers include CIMP and many other candidates such as SERP, p14, p16, LINE-1, and RASSF1A. The number of proliferation-related long non-coding RNAs (e.g., SNHG1, SNHG6, MALAT-1, CRNDE) and microRNAs (e.g., miR-20a, miR-21, miR-143, miR-145, miR-181a/b) that could serve as potential CRC markers has also steadily increased in recent years. Among the immunohistochemical (IHC) proliferative markers, the prognostic value regarding the patients' overall survival (OS) or disease-free survival (DFS) has been confirmed for thymidylate synthase (TS), cyclin B1, cyclin D1, proliferating cell nuclear antigen (PCNA), and Ki-67. In most cases, the overexpression of these markers in tissues was related to worse OS and DFS. However, slowly proliferating cells should also be considered in CRC therapy (especially radiotherapy) as they could represent a reservoir from which cells are recruited to replenish the rapidly proliferating population in response to cell-damaging factors. Considering the above, the aim of this article is to review the most common proliferative markers assessed using various methods including IHC and selected molecular biology techniques (e.g., qRT-PCR, in situ hybridization, RNA/DNA sequencing, next-generation sequencing) as prognostic and predictive markers in CRC.
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Affiliation(s)
- Aldona Kasprzak
- Department of Histology and Embryology, University of Medical Sciences, Swiecicki Street 6, 60-781 Poznan, Poland
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11
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Săsăran MO, Bănescu C. Role of salivary miRNAs in the diagnosis of gastrointestinal disorders: a mini-review of available evidence. Front Genet 2023; 14:1228482. [PMID: 37456668 PMCID: PMC10346860 DOI: 10.3389/fgene.2023.1228482] [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: 05/30/2023] [Accepted: 06/20/2023] [Indexed: 07/18/2023] Open
Abstract
MiRNAs are short, non-coding RNA molecules, which are involved in the regulation of gene expression and which play an important role in various biological processes, including inflammation and cell cycle regulation. The possibility of detecting their extracellular expression, within body fluids, represented the main background for their potential use as non-invasive biomarkers of various diseases. Salivary miRNAs particularly gained interest recently due to the facile collection of stimulated/unstimulated saliva and their stability among healthy subjects. Furthermore, miRNAs seem to represent biomarker candidates of gastrointestinal disorders, with miRNA-based therapeutics showing great potential in those conditions. This review aimed to highlight available evidence on the role of salivary miRNAs in different gastrointestinal conditions. Most salivary-based miRNA studies available in the literature that focused on pathologies of the gastrointestinal tract have so far been conducted on pancreatic cancer patients and delivered reliable results. A few studies also showed the diagnostic utility of salivary miRNAs in conditions such as esophagitis, esophageal cancer, colorectal cancer, or inflammatory bowel disease. Moreover, several authors showed that salivary miRNAs may confidently be used as biomarkers of gastric cancer, but the use of salivary miRNA candidates in gastric inflammation and pre-malignant lesions, essential stages of Correa's cascade, is still put into question. On the other hand, besides miRNAs, other salivary omics have shown biomarker potential in gastro-intestinal conditions. The limited available data suggest that salivary miRNAs may represent reliable biomarker candidates for gastrointestinal conditions. However, their diagnostic potential requires validation through future research, performed on larger cohorts.
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Affiliation(s)
- Maria Oana Săsăran
- Department of Pediatrics 3, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology of Târgu Mureș, Târgu Mureș, Romania
| | - Claudia Bănescu
- Genetics Department, Center for Advanced Medical and Pharmaceutical Research, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureș, Targu Mures, Romania
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12
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Zhang Z, Huang Y, Li J, Su F, Kuo JC, Hu Y, Zhao X, Lee RJ. Antitumor Activity of Anti-miR-21 Delivered through Lipid Nanoparticles. Adv Healthc Mater 2023; 12:e2202412. [PMID: 36412002 PMCID: PMC11468686 DOI: 10.1002/adhm.202202412] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2022] [Revised: 11/17/2022] [Indexed: 11/23/2022]
Abstract
The ability of lipid nanoparticles (LNPs) to deliver nucleic acids have shown a great therapeutic potential to treat a variety of diseases. Here, an optimized formulation of QTsome lipid nanoparticles (QTPlus) is utilized to deliver an anti-miR-21 (AM21) against cancer. The miR-21 downstream gene regulation and antitumor activity is evaluated using mouse and human cancer cells and macrophages. The antitumor activity of QTPlus encapsulating AM21 (QTPlus-AM21) is further evaluated in combination with erlotinib and atezolizumab (ATZ). QTPlus-AM21 demonstrates a superior miR-21-dependent gene regulation and eventually inhibits A549 non-small cell lung cancer growth in vitro. QTPlus-AM21 further induces chemo-sensitization of A549 cells to erlotinib with a combination index of 0.6 in inhibiting A549 cell growth. When systemically administers to MC38 tumor-bearing mouse model, QTPlus-AM21 exhibits an antitumor immune response with over 80% tumor growth inhibition (TGI%) and over twofold and fourfold PD-1 and PD-L1 upregulation in tumors and spleens. The combination therapy of QTPlus-AM21 and ATZ further shows a higher antitumor response (TGI% over 90%) and successfully increases M1 macrophages and CD8 T cells into TME. This study provides new insights into the antitumor mechanism of AM21 and shows great promise of QTPlus-AM21 in combination with chemotherapies and immunotherapies.
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Affiliation(s)
- Zhongkun Zhang
- Division of Pharmaceutics and PharmacologyCollege of PharmacyThe Ohio State University500 W 12th AvenueColumbusOH43210USA
| | - Yirui Huang
- Division of Pharmaceutics and PharmacologyCollege of PharmacyThe Ohio State University500 W 12th AvenueColumbusOH43210USA
| | - Jing Li
- Zhejiang Haichang Biotechnology Co., Ltd.HangzhouZhejiang310000P. R. China
| | - Fei Su
- Zhejiang Haichang Biotechnology Co., Ltd.HangzhouZhejiang310000P. R. China
| | - Jimmy Chun‐Tien Kuo
- Division of Pharmaceutics and PharmacologyCollege of PharmacyThe Ohio State University500 W 12th AvenueColumbusOH43210USA
| | - Yingwen Hu
- The Whiteoak Group, Inc.RockvilleMD20855USA
| | | | - Robert J. Lee
- Division of Pharmaceutics and PharmacologyCollege of PharmacyThe Ohio State University500 W 12th AvenueColumbusOH43210USA
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13
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Shen D, Hong Y, Feng Z, Chen X, Cai Y, Peng Q, Tu J. Development of dynamical network biomarkers for regulation in Epstein-Barr virus positive peripheral T cell lymphoma unspecified type. Front Genet 2022; 13:966247. [PMID: 36544484 PMCID: PMC9760704 DOI: 10.3389/fgene.2022.966247] [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: 06/10/2022] [Accepted: 11/24/2022] [Indexed: 12/12/2022] Open
Abstract
Background: This study was performed to identify key regulatory network biomarkers including transcription factors (TFs), miRNAs and lncRNAs that may affect the oncogenesis of EBV positive PTCL-U. Methods: GSE34143 dataset was downloaded and analyzed to identify differentially expressed genes (DEGs) between EBV positive PTCL-U and normal samples. Gene ontology and pathway enrichment analyses were performed to illustrate the potential function of the DEGs. Then, key regulators including TFs, miRNAs and lncRNAs involved in EBV positive PTCL-U were identified by constructing TF-mRNA, lncRNA-miRNA-mRNA, and EBV encoded miRNA-mRNA regulatory networks. Results: A total of 96 DEGs were identified between EBV positive PTCL-U and normal tissues, which were related to immune responses, B cell receptor signaling pathway, chemokine activity. Pathway analysis indicated that the DEGs were mainly enriched in cytokine-cytokine receptor interaction and chemokine signaling pathway. Based on the TF network, hub TFs were identified regulate the target DEGs. Afterwards, a ceRNA network was constructed, in which miR-181(a/b/c/d) and lncRNA LINC01744 were found. According to the EBV-related miRNA regulatory network, CXCL10 and CXCL11 were found to be regulated by EBV-miR-BART1-3p and EBV-miR-BHRF1-3, respectively. By integrating the three networks, some key regulators were found and may serve as potential network biomarkers in the regulation of EBV positive PTCL-U. Conclusion: The network-based approach of the present study identified potential biomarkers including transcription factors, miRNAs, lncRNAs and EBV-related miRNAs involved in EBV positive PTCL-U, assisting us in understanding the molecular mechanisms that underlie the carcinogenesis and progression of EBV positive PTCL-U.
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Affiliation(s)
- Dan Shen
- Department of Oncology, The Third Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yin Hong
- Department of Cardiothoracic Surgery, Suzhou BenQ Hospital, Suzhou, China
| | - Zhengyang Feng
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Xiangying Chen
- Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yuxing Cai
- Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Qiliang Peng
- Department of Radiotherapy and Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China,*Correspondence: Jian Tu, ; Qiliang Peng,
| | - Jian Tu
- Department of Pathology, The Second Affiliated Hospital of Soochow University, Suzhou, China,*Correspondence: Jian Tu, ; Qiliang Peng,
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14
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Circular Sponge against miR-21 Enhances the Antitumor Activity of Doxorubicin against Breast Cancer Cells. Int J Mol Sci 2022; 23:ijms232314803. [PMID: 36499129 PMCID: PMC9736351 DOI: 10.3390/ijms232314803] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Revised: 11/21/2022] [Accepted: 11/23/2022] [Indexed: 12/02/2022] Open
Abstract
Breast cancer is the most common type of cancer in women, with chemotherapy being the main strategy. However, its effectiveness is reduced by drug resistance mechanisms. miR-21 is upregulated in breast cancer that has been linked to drug resistance and carcinogenic processes. Our aim was to capture miR-21 with a circular sponge (Circ-21) and thus inhibit the carcinogenic processes and drug resistance mechanisms in which it participates. Proliferation, migration, colony formation, cell cycle, and poly [ADP-ribose] polymerase 1 (PARP-1) and vascular endothelial growth factor (VEGF) detection assays were performed with MCF7 breast cancer cells and MCF10A non-tumor cells. In addition, doxorubicin resistance tests and detection of drug resistance gene expression were performed in MCF7 cells. Reduction in proliferation, as well as migration and colony formation, increased PARP-1 expression, inhibition of VEGF expression and cell cycle arrest in G2/M phase were displayed in the Circ-21 MCF7, which were not observed in the MCF10A cells. Furthermore, in the MCF7 cells, the Circ-21 enhanced the antitumor activity of doxorubicin and decreased the expression of resistance genes: ABCA1, ABCC4, and ABCC5. Based on these results, the use of Circ-21 can be considered a first step for the establishment of an effective gene therapy in the treatment of breast cancer.
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15
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Gao H, Shen Y, Feng Z, Cai Y, Yang J, Zhu Y, Peng Q. The clinical implications of circulating microRNAs as potential biomarkers in screening oral squamous cell carcinoma. Front Oncol 2022; 12:965357. [PMID: 36465364 PMCID: PMC9714623 DOI: 10.3389/fonc.2022.965357] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 10/26/2022] [Indexed: 01/31/2025] Open
Abstract
BACKGROUND Recent studies have highlighted the biomarker role of circulating miRNAs in oral squamous cell carcinoma (OSCC), indicating their potential application as early diagnostic markers for OSCC. However, the diagnostic results have proven inconclusive. This study was conducted to evaluate the diagnostic value of circulating miRNAs for OSCC diagnosis. METHODS Eligible published studies were identified by a literature search carried out in several databases by using combinations of keywords associated with OSCC, circulating miRNAs, and diagnosis. The bivariate meta-analysis model was adopted to summarize the pooled parameters. Afterwards, we thoroughly explored the sources of heterogeneity after evaluating the risk of bias. RESULTS A total of 60 studies focusing on 41 circulating miRNAs were included. The pooled sensitivity, specificity, and AUC were 0.75 (95%CI: 0.69-0.80), 0.76 (0.70-0.81), 0.82 (0.79-0.85), respectively. Subgroup analyses showed that miRNA combinations were more accurate than single miRNAs. Additionally, plasma may be a better matrix for miRNAs assays in OSCC diagnosis as the plasma-based miRNA assay had a higher level of diagnostic accuracy than serum-based miRNA assay. Subgroup analyses also suggested that using circulating miRNAs for OSCC diagnosis is more effective in Caucasians than in Asian ethnic groups. Finally, circulating miRNA assays based on large sample sizes have superior diagnostic accuracy than small sample sizes. CONCLUSION Circulating miRNAs might be applied as effective surrogate biomarkers for early diagnosis of OSCC. Nevertheless, future larger-scale prospective studies should be performed to enhance the diagnostic efficiency and investigate the miRNA combinations with more pronounced accuracy.
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Affiliation(s)
- Huan Gao
- Center of Stomatology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yi Shen
- Department of Radiation Oncology, Suzhou Science & Technology Town Hospital, Suzhou, China
| | - Zhengyang Feng
- Department of Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yuxing Cai
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Jianxin Yang
- Center of Stomatology, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yaqun Zhu
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Qiliang Peng
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
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16
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Identification of a Five-MiRNA Expression Assay to Aid Colorectal Cancer Diagnosis. GASTROINTESTINAL DISORDERS 2022. [DOI: 10.3390/gidisord4030018] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Introduction: One-third of colorectal cancer (CRC) patients present with advanced disease, and establishing control remains a challenge. Identifying novel biomarkers to facilitate earlier diagnosis is imperative in enhancing oncological outcomes. We aimed to create miRNA oncogenic signature to aid CRC diagnosis. Methods: Tumour and tumour-associated normal (TAN) were extracted from 74 patients during surgery for CRC. RNA was isolated and target miRNAs were quantified using real-time reverse transcriptase polymerase chain reaction. Regression analyses were performed in order to identify miRNA targets capable of differentiating CRC from TAN and compared with two endogenous controls (miR-16 and miR-345) in each sample. Areas under the curve (AUCs) in Receiver Operating Characteristic (ROC) analyses were determined. Results: MiR-21 (β-coefficient:3.661, SE:1.720, p = 0.033), miR-31 (β-coefficient:2.783, SE:0.918, p = 0.002), and miR-150 (β-coefficient:−4.404, SE:0.526, p = 0.004) expression profiles differentiated CRC from TAN. In multivariable analyses, increased miR-31 (β-coefficient:2.431, SE:0.715, p < 0.001) and reduced miR-150 (β-coefficient:−4.620, SE:1.319, p < 0.001) independently differentiated CRC from TAN. The highest AUC generated for miR-21, miR-31, and miR-150 in an oncogenic expression assay was 83.0% (95%CI: 61.7–100.0, p < 0.001). In the circulation of 34 independent CRC patients and 5 controls, the mean expression of miR-21 (p = 0.001), miR-31 (p = 0.001), and miR-150 (p < 0.001) differentiated CRC from controls; however, the median expression of miR-21 (p = 0.476), miR-31 (p = 0.933), and miR-150 (p = 0.148) failed to differentiate these groups. Conclusion: This study identified a five-miRNA signature capable of distinguishing CRC from normal tissues with a high diagnostic test accuracy. Further experimentation with this signature is required to elucidate its diagnostic relevance in the circulation of CRC patients.
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Muthupandian S, Muralidharan M, Madhavan Y, Hariharan NM. Prospective role of salivary MicroRNA for early detection - personalized therapy of head and neck squamous cell carcinoma. Oral Oncol 2022; 134:106063. [PMID: 35964556 DOI: 10.1016/j.oraloncology.2022.106063] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2022] [Accepted: 08/04/2022] [Indexed: 11/19/2022]
Affiliation(s)
- Saravanan Muthupandian
- AMR and Nanomedicine Laboratory, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai 600077, Tamil Nadu, India
| | - Manjusha Muralidharan
- AMR and Nanomedicine Laboratory, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai 600077, Tamil Nadu, India
| | - Yasasve Madhavan
- AMR and Nanomedicine Laboratory, Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences (SIMATS), Chennai 600077, Tamil Nadu, India
| | - N M Hariharan
- Department of Biotechnology, Sree Sastha Institute of Engineering and Technology, Chembarambakkam, 600 123 Tamil Nadu, India.
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18
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Ferris WF. The Role and Interactions of Programmed Cell Death 4 and its Regulation by microRNA in Transformed Cells of the Gastrointestinal Tract. Front Oncol 2022; 12:903374. [PMID: 35847932 PMCID: PMC9277020 DOI: 10.3389/fonc.2022.903374] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2022] [Accepted: 05/30/2022] [Indexed: 11/26/2022] Open
Abstract
Data from GLOBOCAN 2020 estimates that there were 19.3 million new cases of cancer and 10.0 million cancer-related deaths in 2020 and that this is predicted to increase by 47% in 2040. The combined burden of cancers of the gastrointestinal (GI) tract, including oesophageal-, gastric- and colorectal cancers, resulted in 22.6% of the cancer-related deaths in 2020 and 18.7% of new diagnosed cases. Understanding the aetiology of GI tract cancers should have a major impact on future therapies and lessen this substantial burden of disease. Many cancers of the GI tract have suppression of the tumour suppressor Programmed Cell Death 4 (PDCD4) and this has been linked to the expression of microRNAs which bind to the untranslated region of PDCD4 mRNA and either inhibit translation or target the mRNA for degradation. This review highlights the properties of PDCD4 and documents the evidence for the regulation of PDCD4 expression by microRNAs in cancers of the GI tract.
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19
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Durante G, Broseghini E, Comito F, Naddeo M, Milani M, Salamon I, Campione E, Dika E, Ferracin M. Circulating microRNA biomarkers in melanoma and non-melanoma skin cancer. Expert Rev Mol Diagn 2022; 22:305-318. [PMID: 35235479 DOI: 10.1080/14737159.2022.2049243] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Skin cancer is the most common type of cancer and is classified in melanoma and non-melanoma cancers, which include basal cell, squamous cell and Merkel cell carcinoma. Specific microRNAs are dysregulated in each skin cancer type. MicroRNAs act as oncogene or tumor suppressor gene regulators and are actively released from tumor cells in the circulation. Cell-free microRNAs serve many, and possibly yet unexplored, functional roles, but their presence and abundance in the blood has been investigated as disease biomarker. Indeed, specific microRNAs can be isolated and quantified in the blood, usually in serum or plasma fractions, where they are uncommonly stable. MicroRNA levels reflect underlying conditions and have been associated with skin cancer presence, stage, evolution, or therapy efficacy. AREAS COVERED In this review, we summarize the state of the art on circulating microRNAs detectable in skin cancer patients including all the studies that performed microRNA identification and quantification in the circulation using appropriate sample size and statistics and providing detailed methodology, with a specific focus on diagnostic and prognostic biomarkers. EXPERT OPINION Circulating microRNAs display a relevant biomarker potential. We expect the development of methodological guidelines and standardized protocols for circulating miRNA quantification in clinical settings.
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Affiliation(s)
- Giorgio Durante
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
| | - Elisabetta Broseghini
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
| | - Francesca Comito
- Oncology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Maria Naddeo
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
| | - Massimo Milani
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.,R&D Cantabria Labs, Difa Cooper, Italy
| | - Irene Salamon
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
| | - Elena Campione
- Dermatology Unit, Department of Systems Medicine, Tor Vergata University Hospital, Rome, Italy
| | - Emi Dika
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy.,Dermatology Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy
| | - Manuela Ferracin
- Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy
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Shen X, Cai Y, Lu L, Huang H, Yan H, Paty PB, Muca E, Ahuja N, Zhang Y, Johnson CH, Khan SA. Asparagine Metabolism in Tumors Is Linked to Poor Survival in Females with Colorectal Cancer: A Cohort Study. Metabolites 2022; 12:metabo12020164. [PMID: 35208238 PMCID: PMC8875032 DOI: 10.3390/metabo12020164] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2022] [Revised: 02/01/2022] [Accepted: 02/05/2022] [Indexed: 01/02/2023] Open
Abstract
The interplay between the sex-specific differences in tumor metabolome and colorectal cancer (CRC) prognosis has never been studied and represents an opportunity to improve patient outcomes. This study examines the link between tumor metabolome and prognosis by sex for CRC patients. Using untargeted metabolomics analysis, abundances of 91 metabolites were obtained from primary tumor tissues from 197 patients (N = 95 females, N = 102 males) after surgical colectomy for stage I-III CRC. Cox Proportional hazard (PH) regression models estimated the associations between tumor metabolome and 5-year overall survival (OS) and recurrence-free survival (RFS), and their interactions with sex. Eleven metabolites had significant sex differences in their associations with 5-year OS, and five metabolites for 5-year RFS. The metabolites asparagine and serine had sex interactions for both OS and RFS. Furthermore, in the asparagine synthetase (ASNS)-catalyzed asparagine synthesis pathway, asparagine was associated with substantially poorer OS (HR (95% CI): 6.39 (1.78–22.91)) and RFS (HR (95% CI): 4.36 (1.39–13.68)) for female patients only. Similar prognostic disadvantages in females were seen in lysophospholipid and polyamine synthesis. Unique metabolite profiles indicated that increased asparagine synthesis was associated with poorer prognosis for females only, providing insight into precision medicine for CRC treatment stratified by sex.
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Affiliation(s)
- Xinyi Shen
- Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT 06510, USA; (X.S.); (L.L.)
| | - Yuping Cai
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA; (Y.C.); (H.H.); (H.Y.); (Y.Z.)
- Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032, China
| | - Lingeng Lu
- Department of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT 06510, USA; (X.S.); (L.L.)
| | - Huang Huang
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA; (Y.C.); (H.H.); (H.Y.); (Y.Z.)
| | - Hong Yan
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA; (Y.C.); (H.H.); (H.Y.); (Y.Z.)
| | - Philip B. Paty
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (P.B.P.); (E.M.)
| | - Engjel Muca
- Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA; (P.B.P.); (E.M.)
| | - Nita Ahuja
- Division of Surgical Oncology, Department of Surgery, Yale University School of Medicine, New Haven, CT 06510, USA;
| | - Yawei Zhang
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA; (Y.C.); (H.H.); (H.Y.); (Y.Z.)
- Department of Surgery, Yale University School of Medicine, New Haven, CT 06510, USA
- National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Caroline H. Johnson
- Department of Environmental Health Sciences, Yale School of Public Health, Yale University, New Haven, CT 06510, USA; (Y.C.); (H.H.); (H.Y.); (Y.Z.)
- Correspondence: (C.H.J.); (S.A.K.)
| | - Sajid A. Khan
- Division of Surgical Oncology, Department of Surgery, Yale University School of Medicine, New Haven, CT 06510, USA;
- Correspondence: (C.H.J.); (S.A.K.)
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21
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Cai S, Ma J, Wang Y, Cai Y, Xie L, Chen X, Yang Y, Peng Q. Biomarker Value of miR-221 and miR-222 as Potential Substrates in the Differential Diagnosis of Papillary Thyroid Cancer Based on Data Synthesis and Bioinformatics Approach. Front Endocrinol (Lausanne) 2022; 12:794490. [PMID: 35197926 PMCID: PMC8859251 DOI: 10.3389/fendo.2021.794490] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2021] [Accepted: 12/31/2021] [Indexed: 12/13/2022] Open
Abstract
Background MicroRNA (miRNA) has been reported to play a critical regulatory role in papillary thyroid carcinomas (PTC). However, the role of miR-221/222 in PTC remains unclear. Here, we performed this study to explore the diagnostic potentials and mechanisms of miR-221/222 in PTC. Methods First, we systematically analyzed the diagnostic value of miR-221/222 in the diagnosis PTC by pooling the published studies. Afterwards, we performed comprehensive bioinformatics analysis including gene ontology analysis, pathway enrichment analysis and protein-protein interaction analysis to explore the potential mechanisms of miR-221/222 involved in PTC. Results The overall sensitivity and specificity of miR-221/222 for PTC were 0.75 (95% CI: 0.70-0.80) and 0.80 (95% CI: 0.76-0.84) respectively with the AUC of 0.85 (95% CI: 0.81-0.88). The diagnostic performance varied among different subgroups including geographical locations, sample sources and sample sizes. Meanwhile, we found that a combination of miR-221/222 and other miRNAs when used in a diagnostic panel could improve the diagnostic accuracy than individual miR-221/222. Moreover, through the bioinformatics analysis, we confirmed that miR-221/222 targets were highly related to the molecular pathogenesis of PTC. The results revealed that miR-221/222 may exert important functions in PTC through thyroid hormone signaling pathway and some other key pathways by regulating some key genes. Conclusion These findings indicated that miR-221/222 have the potential to serve as auxiliary tools for diagnosing PTC. Further prospective clinical trials should be performed to assess the accuracy of these findings in a larger cohort and determine the clinical uses.
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Affiliation(s)
- Shang Cai
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Jiayan Ma
- Department of Experimental Center, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Yong Wang
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Yuxing Cai
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Liwei Xie
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Xiangying Chen
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Yingying Yang
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
| | - Qiliang Peng
- Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China
- Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China
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Powrózek T, Ochieng Otieno M. Blood Circulating Non-Coding RNAs for the Clinical Management of Triple-Negative Breast Cancer. Cancers (Basel) 2022; 14:803. [PMID: 35159070 PMCID: PMC8833777 DOI: 10.3390/cancers14030803] [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: 01/21/2022] [Revised: 02/02/2022] [Accepted: 02/03/2022] [Indexed: 02/06/2023] Open
Abstract
Triple negative breast cancer (TNBC) represents the most aggressive subtype of breast cancer, and is related to unfavorable prognosis and limited treatment strategies. Currently, there is a lack of reliable biomarkers allowing for the clinical management of TNBC. This is probably caused by a complex molecular background, leading to the development and establishment of a unique tumor phenotype. Recent studies have reported non-coding RNAs (ncRNAs) not only as the most promising class of molecular agents with a high applicability to manage human cancers, including TNBC, but also as robust and non-invasive biomarkers that are able to be monitored in blood circulation, with the application of liquid biopsy. There is a lack of papers discussing the role of blood-circulating ncRNAs as diagnostic, predictive, and prognostic biomarkers for TNBC. In this paper, we summarized the available literature reports on the utility of blood-circulating ncRNAs for TNBC management. Additionally, we supplemented this review by bioinformatics analysis, for better understanding of the role of ncRNAs' machinery in the development of a unique TNBC phenotype.
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Affiliation(s)
- Tomasz Powrózek
- Department of Human Physiology, Medical University of Lublin, 20-080 Lublin, Poland
| | - Michael Ochieng Otieno
- Haematological Malignancies H12O Clinical Research Unit, Spanish National Cancer Research Centre, 28029 Madrid, Spain;
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23
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Liu S, Huo Y, Fan L, Ning B, Sun T, Gao Z. Rapid and ultrasensitive detection of DNA and microRNA-21 using a zirconium porphyrin metal-organic framework-based switch fluorescence biosensor. Anal Chim Acta 2022; 1192:339340. [PMID: 35057960 DOI: 10.1016/j.aca.2021.339340] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 10/19/2021] [Accepted: 11/28/2021] [Indexed: 01/15/2023]
Abstract
Sensitive and accurate detection of nucleic acid biomarkers is critical for early cancer diagnosis, disease monitoring, and clinical treatment. In this study, we developed a switch fluorescence biosensor for simple and high-efficient detection of nucleic acid biomarkers using 6-carboxyfluorescein (FAM)-modified single-stranded DNA (ssDNA) probes (FAM-P1/P2), and zirconium porphyrin metal-organic framework nanoparticles (ZrMOF) acted as fluorescence quencher. FAM-P1/P2 probes were adsorbed on ZrMOF surface because of π-π stacking, hydrogen bonding, and electrostatic interactions. Fluorescence quenching event occurred by fluorescence resonance energy transfer (FRET) and photo-induced electron transfer (PET) processes, thereby achieving the "off" fluorescence status. Once the specific binding was formed between the fluorescence probes and the targets, the rigid double-stranded DNA (dsDNA) structures were released from ZrMOF surface, resulting in the recovery of fluorescence and the "on" status. Because of the superior adsorption ability of ZrMOF toward ssDNA than dsDNA, the switch of fluorescence signals from "off" to "on" allowed rapid and ultrasensitive detection of ssDNA (T1) and microRNA-21 (miR-21) within 30 min. The limit of detection (signal-to-noise ratio = 3) for T1 and miR-21 were 2 fM and 11 aM, respectively. Moreover, the proposed strategy was very simple as it worked by the facile adsorption-quenching-recovery mechanism without difficult and complicated immobilization processes. Also, this biosensor showed an excellent analytical performance in the detection of miR-21 in human serum samples. Therefore, this biosensor might be considered a potential tool for the detection of DNA and miRNA biomarkers in clinical samples.
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Affiliation(s)
- Sha Liu
- Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, China.
| | - Yapeng Huo
- Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, China
| | - Longxing Fan
- Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, China
| | - Baoan Ning
- Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, China
| | - Tieqiang Sun
- Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, China.
| | - Zhixian Gao
- Tianjin Key Laboratory of Risk Assessment and Control Technology for Environment and Food Safety, Tianjin Institute of Environmental and Operational Medicine, Tianjin, 300050, China.
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24
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Kampoli K, Foukas PG, Ntavatzikos A, Arkadopoulos N, Koumarianou A. Interrogating the interplay of angiogenesis and immunity in metastatic colorectal cancer. World J Methodol 2022; 12:43-53. [PMID: 35117981 PMCID: PMC8790311 DOI: 10.5662/wjm.v12.i1.43] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/30/2021] [Revised: 08/17/2021] [Accepted: 12/28/2021] [Indexed: 02/06/2023] Open
Abstract
Colon cancer is the third most common malignancy and the fifth most frequent cause of death from neoplastic disease worldwide. At the time of diagnosis, more than 20% of patients already have metastatic disease. In the last 20 years, the natural course of the disease has changed due to major changes in the management of metastatic disease such as the advent of novel surgical and local therapy approaches as well as the introduction of novel chemotherapy drugs and targeted agents such as anti-epidermal growth factor receptor, anti-BRAF and antiangiogenics. Angiogenesis is a complex biological process of new vessel formation from existing ones and is an integral component of tumor progression supporting cancer cells to grow, proliferate and metastasize. Many molecules are involved in this proangiogenic process, such as vascular endothelial growth factor and its receptors on endothelial cells. A well-standardized methodology that is applied to assess angiogenesis in the tumor microenvironment is microvascular density by using immunohistochemistry with antibodies against endothelial CD31, CD34 and CD105 antigens. Even smaller molecules, such as the microRNAs, which are small non-coding RNAs, are being studied for their usefulness as surrogate biomarkers of angiogenesis and prognosis. In this review, we will discuss recent advances regarding the investigation of angiogenesis, the crosstalk between elements of the immune microenvironment and angiogenesis and how a disorganized tumor vessel network affects the trafficking of CD8+ T cells in the tumor bed. Furthermore, we will present recent data from clinical trials that combine antiangiogenic therapies with immune checkpoint inhibitors in colorectal cancer.
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Affiliation(s)
- Katerina Kampoli
- Hematology Oncology Unit, The Fourth Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Haidari 12462, Athens, Greece
| | - Periklis G Foukas
- The Second Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Haidari 12462, Athens, Greece
| | - Anastasios Ntavatzikos
- Hematology Oncology Unit, The Fourth Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Haidari 12462, Athens, Greece
| | - Nikolaos Arkadopoulos
- The Fourth Surgical Clinic, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Haidari 12462, Athens, Greece
| | - Anna Koumarianou
- Hematology Oncology Unit, The Fourth Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Attikon University Hospital, Haidari 12462, Athens, Greece
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25
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Yang L, Cullin C, Elezgaray J. Detection of short DNA sequences with DNA nanopores. Chemphyschem 2022; 23:e202200021. [DOI: 10.1002/cphc.202200021] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Indexed: 11/06/2022]
Affiliation(s)
- Luyan Yang
- UMR5031: Centre de Recherche Paul Pascal soft matter FRANCE
| | - Christophe Cullin
- CBMN: Chimie et Biologie des Membranes et des Nanoobjets Biology FRANCE
| | - Juan Elezgaray
- CBMN, UMR 5248, CNRS Allé Saint Hilaire, Batiment B14 33600 Pessac FRANCE
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26
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Circulating MicroRNAs as Cancer Biomarkers in Liquid Biopsies. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2022; 1385:23-73. [DOI: 10.1007/978-3-031-08356-3_2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
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27
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Prognostic value of miR-21 for prostate cancer: a systematic review and meta-analysis. Biosci Rep 2021; 42:230521. [PMID: 34931228 PMCID: PMC8753345 DOI: 10.1042/bsr20211972] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2021] [Revised: 12/06/2021] [Accepted: 12/20/2021] [Indexed: 12/09/2022] Open
Abstract
Elevated levels of miR-21 expression are associated with many cancers, suggesting it may be a promising clinical biomarker. In prostate cancer (PCa), however, there is still no consensus about the usefulness of miR-21 as an indicator of disease progression. This systematic review and meta-analysis was conducted to investigate the value of miR-21 expression as a prognostic measurement in PCa patients. Medline (Ovid), EMBASE, Web of Science, Scopus and Cochrane Library databases were systematically searched for relevant publications between 2010 to 2021. Studies exploring the relationship between miR-21 expression, PCa prognosis and clinicopathological factors were selected for review. Those reporting hazard ratio (HR) and 95% confidence intervals (CIs) were subject to meta-analyses. Fixed-effect models were employed to calculated pooled HRs and 95% CIs. Risk of bias in each study was assessed using QUIPS tool. Certainty of evidence in each meta-analysis was assessed using GRADE guidelines. A total of 64 studies were included in the systematic review. Of these, 11 were eligible for inclusion in meta-analysis. Meta-analyses revealed that high miR-21 expression was associated with poor prognosis: HR = 1.58 (95% CI = 1.19–2.09) for biochemical recurrence, MODERATE certainty; HR = 1.46 (95% CI = 1.06–2.01) for death, VERY LOW certainty; and HR = 1.26 (95% CI = 0.70–2.27) for disease progression, VERY LOW certainty. Qualitative summary revealed elevated miR-21 expression was significantly positively associated with PCa stage, Gleason score and risk groups. This systematic review and meta-analysis suggests that elevated levels of miR-21 are associated with poor prognosis in PCa patients. miR-21 expression may therefore be a useful prognostic biomarker in this disease.
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28
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Calvo-López T, Paz-Cabezas M, Llovet P, Ibañez MD, Sastre J, Alonso-Orduña V, Viéitez JM, Yubero A, Vera R, Asensio-Martínez E, Garcia-Alfonso P, Aranda E, Diaz-Rubio E, Perez-Villamil B. Association of miR-21 and miR-335 to microsatellite instability and prognosis in stage III colorectal cancer. Cancer Biomark 2021; 34:201-210. [PMID: 34958006 DOI: 10.3233/cbm-210353] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND MicroRNAs (miRs) are frequently altered in colorectal cancer (CRC) and can be used as prognostic factors. OBJECTIVE To confirm in stage III CRC patients a reported miR signature that was associated to the presence of metastatic disease. To correlate miR expression with microsatellite instability (MSI) and mutations in RAS and BRAF. METHODS miR-21, miR-135a, miR-206, miR-335 and miR-Let-7a expression was analyzed by RT-qPCR in 150 patients out of the 329 patients used to analyze MSI and RAS and BRAF mutations. Association with disease free survival (DFS) and overall survival (OS) was analyzed. Data was confirmed by a multivariate analysis. RESULTS MiR-21 high expression (p= 0.034) and miR-335 low expression (p= 0.0061) were significantly associated with MSI-H. A positive trend (p= 0.0624) between miR-135a high expression and RAS mutations was found. Lower miR-21 expression levels are associated with DFS (HR = 2.654, 95% CI: 1.066-6.605, p= 0.036) and a trend with OS (HR = 2.419, 95% CI: 0.749-7.815, p= 0.140). MiR-21 high expression significantly improves DFS of the poor prognosis group (T4 or N2) (p= 0.03). CONCLUSIONS Association of increased expression of miR-21 and better prognosis in the poor prognostic group may be of interest and could be explored in future prospective clinical trials.
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Affiliation(s)
- Tania Calvo-López
- Genomics and Microarrays Lab, Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain
| | - Mateo Paz-Cabezas
- Genomics and Microarrays Lab, Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain
| | - Patricia Llovet
- Genomics and Microarrays Lab, Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain
| | - Maria Dolores Ibañez
- Genomics and Microarrays Lab, Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain
| | - Javier Sastre
- Genomics and Microarrays Lab, Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain
| | - Vicente Alonso-Orduña
- Hospital Universitario Miguel Servet, Instituto de Investigacion Sanitaria de Aragon (IISA), Zaragoza, Spain
| | - J Ma Viéitez
- Hospital Universitario Central de Asturias, Oviedo, Spain
| | - Alfonso Yubero
- Hospital Clinico Universitario Lozano Blesa, Zaragoza, Spain
| | - Ruth Vera
- Complejo Hospitalario de Navarra, Pamplona, Spain
| | | | | | - Enrique Aranda
- IMIBIC, CIBERONC, ISCIII, Hospital Universitario Reina Sofia, Cordoba, Spain
| | - Eduardo Diaz-Rubio
- Genomics and Microarrays Lab, Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain
| | - Beatriz Perez-Villamil
- Genomics and Microarrays Lab, Medical Oncology Department, Instituto de Investigación Sanitaria San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain
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29
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Almeida-Lousada H, Mestre A, Ramalhete S, Price AJ, de Mello RA, Marreiros AD, Neves RPD, Castelo-Branco P. Screening for Colorectal Cancer Leading into a New Decade: The "Roaring '20s" for Epigenetic Biomarkers? Curr Oncol 2021; 28:4874-4893. [PMID: 34898591 PMCID: PMC8628779 DOI: 10.3390/curroncol28060411] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/01/2021] [Revised: 11/12/2021] [Accepted: 11/17/2021] [Indexed: 12/16/2022] Open
Abstract
Colorectal cancer (CRC) has an important bearing (top five) on cancer incidence and mortality in the world. The etiology of sporadic CRC is related to the accumulation of genetic and epigenetic alterations that result in the appearance of cancer hallmarks such as abnormal proliferation, evasion of immune destruction, resistance to apoptosis, replicative immortality, and others, contributing to cancer promotion, invasion, and metastasis. It is estimated that, each year, at least four million people are diagnosed with CRC in the world. Depending on CRC staging at diagnosis, many of these patients die, as CRC is in the top four causes of cancer death in the world. New and improved screening tests for CRC are needed to detect the disease at an early stage and adopt patient management strategies to decrease the death toll. The three pillars of CRC screening are endoscopy, radiological imaging, and molecular assays. Endoscopic procedures comprise traditional colonoscopy, and more recently, capsule-based endoscopy. The main imaging modality remains Computed Tomography (CT) of the colon. Molecular approaches continue to grow in the diversity of biomarkers and the sophistication of the technologies deployed to detect them. What started with simple fecal occult blood tests has expanded to an armamentarium, including mutation detection and identification of aberrant epigenetic signatures known to be oncogenic. Biomarker-based screening methods have critical advantages and are likely to eclipse the classical modalities of imaging and endoscopy in the future. For example, imaging methods are costly and require highly specialized medical personnel. In the case of endoscopy, their invasiveness limits compliance from large swaths of the population, especially those with average CRC risk. Beyond mere discomfort and fear, there are legitimate iatrogenic concerns associated with endoscopy. The risks of perforation and infection make endoscopy best suited for a confirmatory role in cases where there are positive results from other diagnostic tests. Biomarker-based screening methods are largely non-invasive and are growing in scope. Epigenetic biomarkers, in particular, can be detected in feces and blood, are less invasive to the average-risk patient, detect early-stage CRC, and have a demonstrably superior patient follow-up. Given the heterogeneity of CRC as it evolves, optimal screening may require a battery of blood and stool tests, where each can leverage different pathways perturbed during carcinogenesis. What follows is a comprehensive, systematic review of the literature pertaining to the screening and diagnostic protocols used in CRC. Relevant articles were retrieved from the PubMed database using keywords including: "Screening", "Diagnosis", and "Biomarkers for CRC". American and European clinical trials in progress were included as well.
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Affiliation(s)
- Hélder Almeida-Lousada
- Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, Portugal; (H.A.-L.); (A.M.); (S.R.); (R.A.d.M.); (A.D.M.)
- Algarve Biomedical Center Research Institute (ABC-RI), 8005-139 Faro, Portugal
| | - André Mestre
- Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, Portugal; (H.A.-L.); (A.M.); (S.R.); (R.A.d.M.); (A.D.M.)
- Algarve Biomedical Center Research Institute (ABC-RI), 8005-139 Faro, Portugal
| | - Sara Ramalhete
- Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, Portugal; (H.A.-L.); (A.M.); (S.R.); (R.A.d.M.); (A.D.M.)
- Algarve Biomedical Center Research Institute (ABC-RI), 8005-139 Faro, Portugal
| | - Aryeh J. Price
- School of Law, University of California, Berkeley, CA 94704, USA;
| | - Ramon Andrade de Mello
- Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, Portugal; (H.A.-L.); (A.M.); (S.R.); (R.A.d.M.); (A.D.M.)
- Division of Medical Oncology, Escola Paulista de Medicina, Federal University of São Paulo (UNIFESP), São Paulo 04037-004, Brazil
- Precision Oncology & Health Economics Group (ONCOPRECH), Post-Graduation Program in Medicine, Nine of July University (UNINOVE), São Paulo 01525-000, Brazil
| | - Ana D. Marreiros
- Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, Portugal; (H.A.-L.); (A.M.); (S.R.); (R.A.d.M.); (A.D.M.)
- Algarve Biomedical Center Research Institute (ABC-RI), 8005-139 Faro, Portugal
| | - Ricardo Pires das Neves
- CNC—Center for Neuroscience and Cell Biology, CIBB—Centre for Innovative Biomedicine and Biotechnology, University of Coimbra, 3004-517 Coimbra, Portugal
- IIIUC—Institute of Interdisciplinary Research, University of Coimbra, 3004-517 Coimbra, Portugal
| | - Pedro Castelo-Branco
- Faculty of Medicine and Biomedical Sciences (FMCB), Campus de Gambelas, University of Algarve, 8005-139 Faro, Portugal; (H.A.-L.); (A.M.); (S.R.); (R.A.d.M.); (A.D.M.)
- Algarve Biomedical Center Research Institute (ABC-RI), 8005-139 Faro, Portugal
- Champalimaud Research Program, Champalimaud Center for the Unknown, 1400-038 Lisbon, Portugal
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30
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Karimpour M, Ravanbakhsh R, Maydanchi M, Rajabi A, Azizi F, Saber A. Cancer driver gene and non-coding RNA alterations as biomarkers of brain metastasis in lung cancer: A review of the literature. Biomed Pharmacother 2021; 143:112190. [PMID: 34560543 DOI: 10.1016/j.biopha.2021.112190] [Citation(s) in RCA: 24] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Revised: 09/08/2021] [Accepted: 09/10/2021] [Indexed: 02/07/2023] Open
Abstract
Brain metastasis (BM) is the most common event in patients with lung cancer. Despite multimodal treatments and advances in systemic therapies, development of BM remains one of the main factors associated with poor prognosis and mortality in patients with lung cancer. Therefore, better understanding of mechanisms involved in lung cancer brain metastasis (LCBM) is of great importance to suppress cancer cells and to improve the overall survival of patients. Several cancer-related genes such as EGFR and KRAS have been proposed as potential predictors of LCBM. In addition, there is ample evidence supporting crucial roles of non-coding RNAs (ncRNAs) in mediating LCBM. In this review, we provide comprehensive information on risk assessment, predictive, and prognostic panels for early detection of BM in patients with lung cancer. Moreover, we present an overview of LCBM molecular mechanisms, cancer driver genes, and ncRNAs which may predict the risk of BM in lung cancer patients. Recent clinical studies have focused on determining mechanisms involved in LCBM and their association with diagnosis, prognosis, and treatment outcomes. These studies have shown that alterations in EGFR, KRAS, BRAF, and ALK, as the most frequent coding gene alterations, and dysregulation of ncRNAs such as miR-423, miR-330-3p, miR-145, piR-651, and MALAT1 can be considered as potential biomarkers of LCBM.
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Affiliation(s)
- Mina Karimpour
- Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran
| | - Reyhaneh Ravanbakhsh
- Department of Aquatic Biotechnology, Artemia and Aquaculture Research Institute, Urmia University, Urmia, Iran
| | - Melika Maydanchi
- Zimagene Medical Genetics Laboratory, Avicenna St., Hamedan, Iran
| | - Ali Rajabi
- Department of Animal Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran
| | - Faezeh Azizi
- Genetics Office, Non-Communicable Disease Control Department, Public Health Department, Ministry of Health and Medical Education, Tehran, Iran
| | - Ali Saber
- Zimagene Medical Genetics Laboratory, Avicenna St., Hamedan, Iran.
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31
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Fukada M, Matsuhashi N, Takahashi T, Sugito N, Heishima K, Yoshida K, Akao Y. Postoperative changes in plasma miR21-5p as a novel biomarker for colorectal cancer recurrence: A prospective study. Cancer Sci 2021; 112:4270-4280. [PMID: 34270831 PMCID: PMC8486189 DOI: 10.1111/cas.15065] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 07/03/2021] [Accepted: 07/13/2021] [Indexed: 01/15/2023] Open
Abstract
Cancer‐related microRNAs (miRNAs) are emerging as promising and noninvasive biomarkers for colorectal cancer (CRC). This study aimed to investigate the usefulness of postoperative changes in plasma miR21‐5p levels for recurrence and progressive disease (PD) after surgical resection. This study was a prospective study of 103 CRC patients who underwent surgical resection. Self‐paired plasma samples collected pre‐operation (Pre), 7 days post‐operation (POD7), 1 month post‐operation (POM1), and 6 months post‐operation (POM6) were analyzed. The miRNA levels were evaluated by quantitative reverse transcription PCR. Among the enrolled patients, ten cases (9.7%) of postoperative recurrence and six cases (5.8%) of postoperative PD occurred at POM6. In the recurrence and PD group, plasma miR21‐5p levels significantly increased (POM1: P < .01, POM6: P < .01, respectively). The area under the curve (AUC) value for postoperative changes in plasma miR21‐5p levels at POM1 and POM6 to discriminate recurrence and PD were 0.675 and 0.715, respectively. Combined analysis with postoperative carcinoembryonic antigen (CEA) level in discriminating recurrence and PD increased AUC values (POM1: 0.715 and POM6: 0.789). Furthermore, multivariate analysis for recurrence and PD after surgical resection showed that postoperative changes in the plasma miR21‐5p level at POM1 and POM6 were independent prognostic factors (POM1: P = .03, POM6: P < .01). The postoperative changes in plasma miR21‐5p level could be a useful noninvasive biomarker for monitoring and predicting recurrence and PD after surgical resection of CRC patients. Furthermore, plasma miR21‐5p can predict recurrence and PD after surgical resection.
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Affiliation(s)
- Masahiro Fukada
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Nobuhisa Matsuhashi
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Takao Takahashi
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Nobuhiko Sugito
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan
| | - Kazuki Heishima
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan
| | - Kazuhiro Yoshida
- Department of Surgical Oncology, Graduate School of Medicine, Gifu University, Gifu, Japan
| | - Yukihiro Akao
- United Graduate School of Drug Discovery and Medical Information Sciences, Gifu University, Gifu, Japan
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32
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Palanca-Ballester C, Rodriguez-Casanova A, Torres S, Calabuig-Fariñas S, Exposito F, Serrano D, Redin E, Valencia K, Jantus-Lewintre E, Diaz-Lagares A, Montuenga L, Sandoval J, Calvo A. Cancer Epigenetic Biomarkers in Liquid Biopsy for High Incidence Malignancies. Cancers (Basel) 2021; 13:cancers13123016. [PMID: 34208598 PMCID: PMC8233712 DOI: 10.3390/cancers13123016] [Citation(s) in RCA: 44] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2021] [Revised: 06/04/2021] [Accepted: 06/11/2021] [Indexed: 02/07/2023] Open
Abstract
Early alterations in cancer include the deregulation of epigenetic events such as changes in DNA methylation and abnormal levels of non-coding (nc)RNAs. Although these changes can be identified in tumors, alternative sources of samples may offer advantages over tissue biopsies. Because tumors shed DNA, RNA, and proteins, biological fluids containing these molecules can accurately reflect alterations found in cancer cells, not only coming from the primary tumor, but also from metastasis and from the tumor microenvironment (TME). Depending on the type of cancer, biological fluids encompass blood, urine, cerebrospinal fluid, and saliva, among others. Such samples are named with the general term "liquid biopsy" (LB). With the advent of ultrasensitive technologies during the last decade, the identification of actionable genetic alterations (i.e., mutations) in LB is a common practice to decide whether or not targeted therapy should be applied. Likewise, the analysis of global or specific epigenetic alterations may also be important as biomarkers for diagnosis, prognosis, and even for cancer drug response. Several commercial kits that assess the DNA promoter methylation of single genes or gene sets are available, with some of them being tested as biomarkers for diagnosis in clinical trials. From the tumors with highest incidence, we can stress the relevance of DNA methylation changes in the following genes found in LB: SHOX2 (for lung cancer); RASSF1A, RARB2, and GSTP1 (for lung, breast, genitourinary and colon cancers); and SEPT9 (for colon cancer). Moreover, multi-cancer high-throughput methylation-based tests are now commercially available. Increased levels of the microRNA miR21 and several miRNA- and long ncRNA-signatures can also be indicative biomarkers in LB. Therefore, epigenetic biomarkers are attractive and may have a clinical value in cancer. Nonetheless, validation, standardization, and demonstration of an added value over the common clinical practice are issues needed to be addressed in the transfer of this knowledge from "bench to bedside".
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Affiliation(s)
- Cora Palanca-Ballester
- Biomarkers and Precision Medicine (UBMP) and Epigenomics Unit, IIS, La Fe, 46026 Valencia, Spain;
| | - Aitor Rodriguez-Casanova
- Cancer Epigenomics, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706 Santiago de Compostela, Spain; (A.R.-C.); (A.D.-L.)
- Roche-CHUS Joint Unit, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), 15706 Santiago de Compostela, Spain
| | - Susana Torres
- CIBERONC, ISCIII, 28029 Madrid, Spain; (S.T.); (S.C.-F.); (F.E.); (E.R.); (K.V.); (E.J.-L.); (L.M.)
- Molecular Oncology Laboratory, Fundación Hospital General Universitario de Valencia, 46014 Valencia, Spain
- TRIAL Mixed Unit, Centro de Investigación Príncipe Felipe-Fundación para la Investigación del Hospital General Universitario de Valencia, 46014 Valencia, Spain
| | - Silvia Calabuig-Fariñas
- CIBERONC, ISCIII, 28029 Madrid, Spain; (S.T.); (S.C.-F.); (F.E.); (E.R.); (K.V.); (E.J.-L.); (L.M.)
- Molecular Oncology Laboratory, Fundación Hospital General Universitario de Valencia, 46014 Valencia, Spain
- TRIAL Mixed Unit, Centro de Investigación Príncipe Felipe-Fundación para la Investigación del Hospital General Universitario de Valencia, 46014 Valencia, Spain
- Department of Pathology, Universitat de València, 46010 Valencia, Spain
| | - Francisco Exposito
- CIBERONC, ISCIII, 28029 Madrid, Spain; (S.T.); (S.C.-F.); (F.E.); (E.R.); (K.V.); (E.J.-L.); (L.M.)
- DISNA and Program in Solid Tumors, Center for Applied Medical Research (CIMA), 31008 Pamplona, Spain;
- Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra, 31008 Pamplona, Spain
| | - Diego Serrano
- DISNA and Program in Solid Tumors, Center for Applied Medical Research (CIMA), 31008 Pamplona, Spain;
- Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra, 31008 Pamplona, Spain
| | - Esther Redin
- CIBERONC, ISCIII, 28029 Madrid, Spain; (S.T.); (S.C.-F.); (F.E.); (E.R.); (K.V.); (E.J.-L.); (L.M.)
- DISNA and Program in Solid Tumors, Center for Applied Medical Research (CIMA), 31008 Pamplona, Spain;
- Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra, 31008 Pamplona, Spain
| | - Karmele Valencia
- CIBERONC, ISCIII, 28029 Madrid, Spain; (S.T.); (S.C.-F.); (F.E.); (E.R.); (K.V.); (E.J.-L.); (L.M.)
- DISNA and Program in Solid Tumors, Center for Applied Medical Research (CIMA), 31008 Pamplona, Spain;
- Department of Biochemistry and Genetics, School of Sciences, University of Navarra, 31008 Pamplona, Spain
| | - Eloisa Jantus-Lewintre
- CIBERONC, ISCIII, 28029 Madrid, Spain; (S.T.); (S.C.-F.); (F.E.); (E.R.); (K.V.); (E.J.-L.); (L.M.)
- Molecular Oncology Laboratory, Fundación Hospital General Universitario de Valencia, 46014 Valencia, Spain
- TRIAL Mixed Unit, Centro de Investigación Príncipe Felipe-Fundación para la Investigación del Hospital General Universitario de Valencia, 46014 Valencia, Spain
- Department of Biotechnology, Universitat Politècnica de València, 46022 Valencia, Spain
| | - Angel Diaz-Lagares
- Cancer Epigenomics, Translational Medical Oncology (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), 15706 Santiago de Compostela, Spain; (A.R.-C.); (A.D.-L.)
- CIBERONC, ISCIII, 28029 Madrid, Spain; (S.T.); (S.C.-F.); (F.E.); (E.R.); (K.V.); (E.J.-L.); (L.M.)
| | - Luis Montuenga
- CIBERONC, ISCIII, 28029 Madrid, Spain; (S.T.); (S.C.-F.); (F.E.); (E.R.); (K.V.); (E.J.-L.); (L.M.)
- DISNA and Program in Solid Tumors, Center for Applied Medical Research (CIMA), 31008 Pamplona, Spain;
- Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra, 31008 Pamplona, Spain
| | - Juan Sandoval
- Biomarkers and Precision Medicine (UBMP) and Epigenomics Unit, IIS, La Fe, 46026 Valencia, Spain;
- Correspondence: (J.S.); (A.C.)
| | - Alfonso Calvo
- CIBERONC, ISCIII, 28029 Madrid, Spain; (S.T.); (S.C.-F.); (F.E.); (E.R.); (K.V.); (E.J.-L.); (L.M.)
- DISNA and Program in Solid Tumors, Center for Applied Medical Research (CIMA), 31008 Pamplona, Spain;
- Department of Pathology, Anatomy and Physiology, School of Medicine, University of Navarra, 31008 Pamplona, Spain
- Correspondence: (J.S.); (A.C.)
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The Clinical Assessment of MicroRNA Diagnostic, Prognostic, and Theranostic Value in Colorectal Cancer. Cancers (Basel) 2021; 13:cancers13122916. [PMID: 34208056 PMCID: PMC8230660 DOI: 10.3390/cancers13122916] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2021] [Revised: 05/29/2021] [Accepted: 06/09/2021] [Indexed: 12/12/2022] Open
Abstract
Simple Summary MiRNAs are of great interest within colorectal cancers in diagnosis, prognosis, and within the field of personalized treatments; they are present within different biological fluids such as blood and can lead to specific information for daily clinical use. Herein, we review the current literature focusing on miRNAs as potential diagnostic and prognostic biomarkers in patients treated for colorectal cancers. Detection and analysis of miRNA expression are cost-effective and lead to high sensitivity and specificity rates. However, it is now necessary to highlight the most sensitive and specific miRNAs for each goal, either diagnostic, prognostic, or theranostic, thanks to multicentric prospective studies. Abstract MiRNAs have recently become a subject of great interest within cancers and especially colorectal cancers in diagnosis, prognosis, and therapy decisions; herein we review the current literature focusing on miRNAs in colorectal cancers, and we discuss future challenges to use this tool on a daily clinical basis. In liquid biopsies, miRNAs seem easily accessible and can give important information toward each step of the management of colorectal cancers. However, it is now necessary to highlight the most sensitive and specific miRNAs for each goal thanks to multicentric prospective studies. Conclusions: by their diversity and the feasibility of their use, miRNAs are getting part of the armamentarium of healthcare management of colorectal cancers.
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Cancer-secreted exosomal miR-21-5p induces angiogenesis and vascular permeability by targeting KRIT1. Cell Death Dis 2021; 12:576. [PMID: 34088891 PMCID: PMC8178321 DOI: 10.1038/s41419-021-03803-8] [Citation(s) in RCA: 102] [Impact Index Per Article: 25.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Revised: 04/27/2021] [Accepted: 04/27/2021] [Indexed: 12/12/2022]
Abstract
Cancer-secreted exosomes are critical mediators of cancer-host crosstalk. In the present study, we showed the delivery of miR-21-5p from colorectal cancer (CRC) cells to endothelial cells via exosomes increased the amount of miR-21-5p in recipient cells. MiR-21-5p suppressed Krev interaction trapped protein 1 (KRIT1) in recipient HUVECs and subsequently activated β-catenin signaling pathway and increased their downstream targets VEGFa and Ccnd1, which consequently promoted angiogenesis and vascular permeability in CRC. A strong inverse correlation between miR-21-5p and KRIT1 expression levels was observed in CRC-adjacent vessels. Furthermore, miR-21-5p expression in circulating exosomes was markedly higher in CRC patients than in healthy donors. Thus, our data suggest that exosomal miR-21-5p is involved in angiogenesis and vascular permeability in CRC and may be used as a potential new therapeutic target.
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Karkhane M, Lashgarian HE, Hormozi M, Fallahi S, Cheraghipour K, Marzban A. Oncogenesis and Tumor Inhibition by MicroRNAs and its Potential Therapeutic Applications: A Systematic Review. Microrna 2021; 9:198-215. [PMID: 31686643 DOI: 10.2174/2211536608666191104103834] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2019] [Revised: 08/01/2019] [Accepted: 10/21/2019] [Indexed: 12/12/2022]
Abstract
MicroRNAs appear as small molecule modifiers, which improve many new findings and mechanical illustrations for critically important biological phenomena and pathologic events. The best-characterized non-coding RNA family consists of about 2600 human microRNAs. Rich evidence has revealed their crucial importance in maintaining normal development, differentiation, growth control, aging, modulation of cell survival or apoptosis, as well as migration and metastasis as microRNAs dysregulation leads to cancer incidence and progression. By far, microRNAs have recently emerged as attractive targets for therapeutic intervention. The rationale for developing microRNA therapeutics is based on the premise that aberrantly expressed microRNAs play a significant role in the emergence of a variety of human diseases ranging from cardiovascular defects to cancer, and that repairing these microRNA deficiencies by either antagonizing or restoring microRNA function may yield a therapeutic benefit. Although microRNA antagonists are conceptually similar to other inhibitory therapies, improving the performance of microRNAs by microRNA replacement or inhibition that is a less well- described attitude. In this assay, we have condensed the last global knowledge and concepts regarding the involvement of microRNAs in cancer emergence, which has been achieved from the previous studies, consisting of the regulation of key cancer-related pathways, such as cell cycle control and the DNA damage response and the disruption of profile expression in human cancer. Here, we have reviewed the special characteristics of microRNA replacement and inhibition therapies and discussed explorations linked with the delivery of microRNA mimics in turmeric cells. Besides, the achievement of biomarkers based on microRNAs in clinics is considered as novel non-invasive biomarkers in diagnostic and prognostic assessments.
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Affiliation(s)
- Maryam Karkhane
- Department of Medical Biotechnology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Hamed Esmaeil Lashgarian
- Department of Medical Biotechnology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Maryam Hormozi
- Department of Biochemistry, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Shirzad Fallahi
- Department of Medical Parasitology and Mycology, School of Medicine, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Kourosh Cheraghipour
- Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
| | - Abdolrazagh Marzban
- Razi Herbal Medicines Research Center, Lorestan University of Medical Sciences, Khorramabad, Iran
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Use of Omics Data in Fracture Prediction; a Scoping and Systematic Review in Horses and Humans. Animals (Basel) 2021; 11:ani11040959. [PMID: 33808497 PMCID: PMC8065418 DOI: 10.3390/ani11040959] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2021] [Revised: 03/25/2021] [Accepted: 03/26/2021] [Indexed: 12/17/2022] Open
Abstract
Simple Summary Despite many recent advances in imaging and epidemiological data analysis, musculoskeletal injuries continue to be a welfare issue in racehorses. Omics studies describe the study of protein, genetic material (both DNA and RNA, including microRNAs—small non-coding ribonucleic acids) and metabolites that may provide insights into the pathophysiology of disease or opportunities to monitor response to treatment when measured in bodily fluids. As these fields of study are scientifically complex and highly specialised, it is timely to perform a review of the current literature to allow for the design of robust studies that allow for repeatable work. Systematic reviews have been introduced into the medical literature and are a methodological way of searching for relevant papers followed by critical review of the content and a detection of biases. The objectives of the current systematic review were to identify and critically appraise the literature pertaining to microRNA (miRNA) and their target genes that are correlated with stress fractures in racehorses and humans. The object was to define a panel of miRNAs and their target genes as potential biomarkers in either horses or human subjects. The online scientific databases were searched and a reviewed was performed according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. MicroRNA profiling studies in horses continue to emerge, but as of yet, no miRNA profile can reliably predict the occurrence of fractures. It is very important that future studies are well designed to mitigate the effects of variation in sample size, exercise and normalisation methods. Abstract Despite many recent advances in imaging and epidemiological data analysis, musculoskeletal injuries continue to be a welfare issue in racehorses. Peptide biomarker studies have failed to consistently predict bone injury. Molecular profiling studies provide an opportunity to study equine musculoskeletal disease. A systematic review of the literature was performed using preferred reporting items for systematic reviews and meta-analyses protocols (PRISMA-P) guidelines to assess the use of miRNA profiling studies in equine and human musculoskeletal injuries. Data were extracted from 40 papers between 2008 and 2020. Three miRNA studies profiling equine musculoskeletal disease were identified, none of which related to equine stress fractures. Eleven papers studied miRNA profiles in osteoporotic human patients with fractures, but differentially expressed miRNAs were not consistent between studies. MicroRNA target prediction programmes also produced conflicting results between studies. Exercise affected miRNA profiles in both horse and human studies (e.g., miR-21 was upregulated by endurance exercise and miR-125b was downregulated by exercise). MicroRNA profiling studies in horses continue to emerge, but as yet, no miRNA profile can reliably predict the occurrence of fractures. It is very important that future studies are well designed to mitigate the effects of variation in sample size, exercise and normalisation methods.
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Ruiz-Bañobre J, Goel A. Genomic and epigenomic biomarkers in colorectal cancer: From diagnosis to therapy. Adv Cancer Res 2021; 151:231-304. [PMID: 34148615 PMCID: PMC10338180 DOI: 10.1016/bs.acr.2021.02.008] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the United States. Despite ongoing efforts aimed at increasing screening for CRC and early detection, and development of more effective therapeutic regimens, the overall morbidity and mortality from this malignancy remains a clinical challenge. Therefore, identifying and developing genomic and epigenomic biomarkers that can improve CRC diagnosis and help predict response to current therapies are of paramount importance for improving survival outcomes in CRC patients, sparing patients from toxicity associated with current regimens, and reducing the economic burden associated with these treatments. Although efforts to develop biomarkers over the past decades have achieved some success, the recent availability of high-throughput analytical tools, together with the use of machine learning algorithms, will likely hasten the development of more robust diagnostic biomarkers and improved guidance for clinical decision-making in the coming years. In this chapter, we provide a systematic and comprehensive overview on the current status of genomic and epigenomic biomarkers in CRC, and comment on their potential clinical significance in the management of patients with this fatal malignancy, including in the context of precision medicine.
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Affiliation(s)
- Juan Ruiz-Bañobre
- Medical Oncology Department, University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela (USC), CIBERONC, Santiago de Compostela, Spain; Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago de Compostela, University of Santiago de Compostela (USC), CIBERONC, Santiago de Compostela, Spain
| | - Ajay Goel
- Department of Molecular Diagnostics and Experimental Therapeutics, Beckman Research Institute of City of Hope Comprehensive Cancer Center, Duarte, CA, United States.
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Balachandra S, Kusin SB, Lee R, Blackwell JM, Tiro JA, Cowell LG, Chiang CM, Wu SY, Varma S, Rivera EL, Mayo HG, Ding L, Sumer BD, Lea JS, Bagrodia A, Farkas LM, Wang R, Fakhry C, Dahlstrom KR, Sturgis EM, Day AT. Blood-based biomarkers of human papillomavirus-associated cancers: A systematic review and meta-analysis. Cancer 2021; 127:850-864. [PMID: 33270909 PMCID: PMC8135101 DOI: 10.1002/cncr.33221] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2020] [Revised: 06/06/2020] [Accepted: 06/14/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Despite the significant societal burden of human papillomavirus (HPV)-associated cancers, clinical screening interventions for HPV-associated noncervical cancers are not available. Blood-based biomarkers may help close this gap in care. METHODS Five databases were searched, 5687 articles were identified, and 3631 unique candidate titles and abstracts were independently reviewed by 2 authors; 702 articles underwent a full-text review. Eligibility criteria included the assessment of a blood-based biomarker within a cohort or case-control study. RESULTS One hundred thirty-seven studies were included. Among all biomarkers assessed, HPV-16 E seropositivity and circulating HPV DNA were most significantly correlated with HPV-associated cancers in comparison with cancer-free controls. In most scenarios, HPV-16 E6 seropositivity varied nonsignificantly according to tumor type, specimen collection timing, and anatomic site (crude odds ratio [cOR] for p16+ or HPV+ oropharyngeal cancer [OPC], 133.10; 95% confidence interval [CI], 59.40-298.21; cOR for HPV-unspecified OPC, 25.41; 95% CI, 8.71-74.06; cOR for prediagnostic HPV-unspecified OPC, 59.00; 95% CI, 15.39-226.25; cOR for HPV-unspecified cervical cancer, 12.05; 95% CI, 3.23-44.97; cOR for HPV-unspecified anal cancer, 73.60; 95% CI, 19.68-275.33; cOR for HPV-unspecified penile cancer, 16.25; 95% CI, 2.83-93.48). Circulating HPV-16 DNA was a valid biomarker for cervical cancer (cOR, 15.72; 95% CI, 3.41-72.57). In 3 cervical cancer case-control studies, cases exhibited unique microRNA expression profiles in comparison with controls. Other assessed biomarker candidates were not valid. CONCLUSIONS HPV-16 E6 antibodies and circulating HPV-16 DNA are the most robustly analyzed and most promising blood-based biomarkers for HPV-associated cancers to date. Comparative validity analyses are warranted. Variations in tumor type-specific, high-risk HPV DNA prevalence according to anatomic site and world region highlight the need for biomarkers targeting more high-risk HPV types. Further investigation of blood-based microRNA expression profiling appears indicated.
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Affiliation(s)
| | | | - Rebecca Lee
- Department of Otolaryngology–Head and Neck Surgery, UT Southwestern Medical Center, Dallas, Texas
| | | | - Jasmin A. Tiro
- Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas
- Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas
| | - Lindsay G. Cowell
- Department of Population and Data Sciences, UT Southwestern Medical Center, Dallas, Texas
- Department of Immunology, UT Southwestern Medical Center, Dallas, Texas
| | - Cheng-Ming Chiang
- Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas
- Department of Biochemistry, UT Southwestern Medical Center, Dallas, Texas
- Department of Pharmacology, UT Southwestern Medical Center, Dallas, Texas
| | - Shwu-Yuan Wu
- Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas
- Department of Biochemistry, UT Southwestern Medical Center, Dallas, Texas
| | - Sanskriti Varma
- Department of Internal Medicine, NewYork-Presbyterian Hospital–Columbia Campus, New York, New York
| | - Erika L. Rivera
- Department of General Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Helen G. Mayo
- Digital Library and Learning Center, UT Southwestern Medical Center, Dallas, Texas
| | - Lianghao Ding
- Department of Radiation Oncology, UT Southwestern Medical Center, Dallas, Texas
| | - Baran D. Sumer
- Department of Otolaryngology–Head and Neck Surgery, UT Southwestern Medical Center, Dallas, Texas
| | - Jayanthi S. Lea
- Department of Obstetrics and Gynecology, UT Southwestern Medical Center, Dallas, Texas
| | - Aditya Bagrodia
- Department of Urology, UT Southwestern Medical Center, Dallas, Texas
| | - Linda M. Farkas
- Department of Surgery, UT Southwestern Medical Center, Dallas, Texas
| | - Richard Wang
- Department of Dermatology, UT Southwestern Medical Center, Dallas, Texas
| | - Carole Fakhry
- Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland
| | - Kristina R. Dahlstrom
- Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Erich M. Sturgis
- Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Andrew T. Day
- Department of Otolaryngology–Head and Neck Surgery, UT Southwestern Medical Center, Dallas, Texas
- Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, Texas
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Lai CY, Yeh KY, Lin CY, Hsieh YW, Lai HH, Chen JR, Hsu CC, Her GM. MicroRNA-21 Plays Multiple Oncometabolic Roles in the Process of NAFLD-Related Hepatocellular Carcinoma via PI3K/AKT, TGF-β, and STAT3 Signaling. Cancers (Basel) 2021; 13:940. [PMID: 33668153 PMCID: PMC7956552 DOI: 10.3390/cancers13050940] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 02/17/2021] [Accepted: 02/17/2021] [Indexed: 12/20/2022] Open
Abstract
MicroRNA-21 (miR-21) is one of the most frequently upregulated miRNAs in liver diseases such as nonalcoholic fatty liver disease (NAFLD) and hepatocellular carcinoma (HCC). However, mechanistic pathways that connect NAFLD and HCC remain elusive. We developed a doxycycline (Dox)-inducible transgenic zebrafish model (LmiR21) which exhibited an upregulation of miR-21 in the liver, which in turn induced the full spectrum of NAFLD, including steatosis, inflammation, fibrosis, and HCC, in the LmiR21 fish. Diethylnitrosamine (DEN) treatment led to accelerated liver tumor formation and exacerbated their aggressiveness. Moreover, prolonged miR-21 expression for up to ten months induced nonalcoholic steatohepatitis (NASH)-related HCC (NAHCC). Immunoblotting and immunostaining confirmed the presence of miR-21 regulatory proteins (i.e., PTEN, SMAD7, p-AKT, p-SMAD3, and p-STAT3) in human nonviral HCC tissues and LmiR21 models. Thus, we demonstrated that miR-21 can induce NAHCC via at least three mechanisms: First, the occurrence of hepatic steatosis increases with the decrease of ptenb, pparaa, and activation of the PI3K/AKT pathway; second, miR-21 induces hepatic inflammation (or NASH) through an increase in inflammatory gene expression via STAT3 signaling pathways, and induces liver fibrosis through hepatic stellate cell (HSC) activation and collagen deposition via TGF-β/Smad3/Smad7 signaling pathways; finally, oncogenic activation of Smad3/Stat3 signaling pathways induces HCC. Our LmiR21 models showed similar molecular pathology to the human cancer samples in terms of initiation of lipid metabolism disorder, inflammation, fibrosis and activation of the PI3K/AKT, TGF-β/SMADs and STAT3 (PTS) oncogenic signaling pathways. Our findings indicate that miR-21 plays critical roles in the mechanistic perspectives of NAHCC development via the PTS signaling networks.
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Affiliation(s)
- Chi-Yu Lai
- Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan; (C.-Y. L.); (C.-Y. L.); (Y.-W.H.)
- Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan;
- Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan
| | - Kun-Yun Yeh
- Division of Hemato-Oncology, Department of Internal Medicine, Chang Gung Memorial Hospital, Keelung 204, Taiwan;
| | - Chiu-Ya Lin
- Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan; (C.-Y. L.); (C.-Y. L.); (Y.-W.H.)
- Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan;
- Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan
| | - Yang-Wen Hsieh
- Department of Bioscience and Biotechnology, National Taiwan Ocean University, Keelung 202, Taiwan; (C.-Y. L.); (C.-Y. L.); (Y.-W.H.)
- Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan;
- Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan
| | - Hsin-Hung Lai
- Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan;
- Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan
| | - Jim-Ray Chen
- Department of Pathology, Chang Gung Memorial Hospital, Keelung 204, Taiwan;
| | - Chia-Chun Hsu
- Department of Radiology, Buddhist Tzu Chi General Hospital, Taichung Branch, Taichung 427, Taiwan;
- School of Medicine, Tzu Chi University, Hualien 970, Taiwan
| | - Guor Mour Her
- Institute of Biopharmaceutical Sciences, National Yang Ming Chiao Tung University, Taipei 112, Taiwan;
- Institute of Biopharmaceutical Sciences, National Yang-Ming University, Taipei 112, Taiwan
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Dos Santos IL, Penna KGBD, Dos Santos Carneiro MA, Libera LSD, Ramos JEP, Saddi VA. Tissue micro-RNAs associated with colorectal cancer prognosis: a systematic review. Mol Biol Rep 2021; 48:1853-1867. [PMID: 33598796 DOI: 10.1007/s11033-020-06075-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Accepted: 12/10/2020] [Indexed: 01/05/2023]
Abstract
Colorectal cancer (CRC) is a multifactorial disease commonly diagnosed worldwide, with high mortality rates. Several studies demonstrate important associations between differential expression of micro-RNAs (miRs) and the prognosis of CRC. The present study aimed to identify differentially expressed tissue miRs associated with prognostic factors in CRC patients, through a systematic review of the Literature. Using the PubMed database, Cochrane Library and Web of Science, studies published in English evaluating miRs differentially expressed in tumor tissue and significantly associated with the prognostic aspects of CRC were selected. All the included studies used RT-PCR (Taqman or SYBR Green) for miR expression analysis and the period of publication was from 2009 to 2018. A total of 115 articles accomplished the inclusion criteria and were included in the review. The studies investigated the expression of 100 different miRs associated with prognostic aspects in colorectal cancer patients. The most frequent oncogenic miRs investigated were miR-21, miR-181a, miR-182, miR-183, miR-210 and miR-224 and the hyperexpression of these miRs was associated with distant metastasis, lymph node metastasis and worse survival in patients with CRC. The most frequent tumor suppressor miRs were miR-126, miR-199b and miR-22 and the hypoexpression of these miRs was associated with distant metastasis, worse prognosis and a higher risk of disease relapse (worse disease-free survival). Specific tissue miRs are shown to be promising prognostic biomarkers in patients with CRC, given their strong association with the prognostic aspects of these tumors, however, new studies are necessary to establish the sensibility and specificity of the individual miRs in order to use them in clinical practice.
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Affiliation(s)
- Igor Lopes Dos Santos
- Programa de Mestrado em Ciências Ambientais e Saúde da Pontifícia Universidade Católica de Goiás, Laboratório de Genética e Biodiversidade, Escola de Ciências Médicas, Farmacêuticas e Biomédicas da Pontifícia Universidade Católica de Goiás, Área IV, Praça Universitária, 1440, Setor Leste Universitário, Goiânia, GO, 74605-010, Brazil.
| | - Karlla Greick Batista Dias Penna
- Programa de Mestrado em Ciências Ambientais e Saúde da Pontifícia Universidade Católica de Goiás, Laboratório de Genética e Biodiversidade, Escola de Ciências Médicas, Farmacêuticas e Biomédicas da Pontifícia Universidade Católica de Goiás, Área IV, Praça Universitária, 1440, Setor Leste Universitário, Goiânia, GO, 74605-010, Brazil
| | | | | | - Jéssica Enocencio Porto Ramos
- Programa de Mestrado em Ciências Ambientais e Saúde da Pontifícia Universidade Católica de Goiás, Laboratório de Genética e Biodiversidade, Escola de Ciências Médicas, Farmacêuticas e Biomédicas da Pontifícia Universidade Católica de Goiás, Área IV, Praça Universitária, 1440, Setor Leste Universitário, Goiânia, GO, 74605-010, Brazil
| | - Vera Aparecida Saddi
- Programa de Mestrado em Ciências Ambientais e Saúde da Pontifícia Universidade Católica de Goiás, Laboratório de Genética e Biodiversidade, Escola de Ciências Médicas, Farmacêuticas e Biomédicas da Pontifícia Universidade Católica de Goiás, Área IV, Praça Universitária, 1440, Setor Leste Universitário, Goiânia, GO, 74605-010, Brazil
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Gallardo-Gómez M, De Chiara L, Álvarez-Chaver P, Cubiella J. Colorectal cancer screening and diagnosis: omics-based technologies for development of a non-invasive blood-based method. Expert Rev Anticancer Ther 2021; 21:723-738. [PMID: 33507120 DOI: 10.1080/14737140.2021.1882858] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Colorectal cancer (CRC) is one of the most important health problems in the Western world. In order to reduce the burden of the disease, two strategies are proposed: screening and prompt detection in symptomatic patients. Although diagnosis and prevention are mainly based on colonoscopy, fecal hemoglobin detection has been widely implemented as a noninvasive strategy. Various studies aiming to discover blood-based biomarkers have recently emerged.Areas covered: The burgeoning omics field provides diverse high-throughput approaches for CRC blood-based biomarker discovery. In this review, we appraise the most robust and commonly used technologies within the fields of genomics, transcriptomics, epigenomics, proteomics, and metabolomics, together with their targeted validation approaches. We summarize the transference process from the discovery phase until clinical translation. Finally, we review the best candidate biomarkers and their potential clinical applicability.Expert opinion: Some available biomarkers are promising, especially in the field of epigenomics: DNA methylation and microRNA. Transference requires the joint collaboration of basic researchers, intellectual property experts, technology transfer officers and clinicians. Blood-based biomarkers will be selected not only based on their diagnostic accuracy and cost but also on their reliability, applicability to clinical analysis laboratories and their acceptance by the population.
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Affiliation(s)
- María Gallardo-Gómez
- Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain.,Biomedical Research Center (CINBIO), University of Vigo, Vigo, Spain
| | - Loretta De Chiara
- Department of Biochemistry, Genetics and Immunology, University of Vigo, Vigo, Spain.,Biomedical Research Center (CINBIO), University of Vigo, Vigo, Spain
| | - Paula Álvarez-Chaver
- Proteomics Unit, Service of Structural Determination, Proteomics and Genomics, Center for Scientific and Technological Research Support (CACTI), University of Vigo, Vigo, Spain
| | - Joaquin Cubiella
- Department of Gastroenterology, Hospital Universitario De Ourense, Ourense, Spain.,Instituto De Investigación Sanitaria Galicia Sur, Ourense, Spain.,Centro De Investigación Biomédica En Red Enfermedades Hepáticas Y Digestivas, Ourense, Spain
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Rodriguez-Casanova A, Costa-Fraga N, Bao-Caamano A, López-López R, Muinelo-Romay L, Diaz-Lagares A. Epigenetic Landscape of Liquid Biopsy in Colorectal Cancer. Front Cell Dev Biol 2021; 9:622459. [PMID: 33614651 PMCID: PMC7892964 DOI: 10.3389/fcell.2021.622459] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Accepted: 01/05/2021] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most common malignancies and is a major cause of cancer-related deaths worldwide. Thus, there is a clinical need to improve early detection of CRC and personalize therapy for patients with this disease. In the era of precision oncology, liquid biopsy has emerged as a major approach to characterize the circulating tumor elements present in body fluids, including cell-free DNA and RNA, circulating tumor cells, and extracellular vesicles. This non-invasive tool has allowed the identification of relevant molecular alterations in CRC patients, including some indicating the disruption of epigenetic mechanisms. Epigenetic alterations found in solid and liquid biopsies have shown great utility as biomarkers for early detection, prognosis, monitoring, and evaluation of therapeutic response in CRC patients. Here, we summarize current knowledge of the most relevant epigenetic mechanisms associated with cancer development and progression, and the implications of their deregulation in cancer cells and liquid biopsy of CRC patients. In particular, we describe the methodologies used to analyze these epigenetic alterations in circulating tumor material, and we focus on the clinical utility of epigenetic marks in liquid biopsy as tumor biomarkers for CRC patients. We also discuss the great challenges and emerging opportunities of this field for the diagnosis and personalized management of CRC patients.
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Affiliation(s)
- Aitor Rodriguez-Casanova
- Cancer Epigenomics Laboratory, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, Spain.,Roche-Chus Joint Unit, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain
| | - Nicolás Costa-Fraga
- Cancer Epigenomics Laboratory, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, Spain
| | - Aida Bao-Caamano
- Cancer Epigenomics Laboratory, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, Spain
| | - Rafael López-López
- Roche-Chus Joint Unit, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), Santiago de Compostela, Spain.,Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, Spain.,Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain
| | - Laura Muinelo-Romay
- Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain.,Liquid Biopsy Analysis Unit, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, Spain
| | - Angel Diaz-Lagares
- Cancer Epigenomics Laboratory, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago (IDIS), University Clinical Hospital of Santiago (CHUS/SERGAS), Santiago de Compostela, Spain.,Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain
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Sabarimurugan S, Madhav MR, Kumarasamy C, Gupta A, Baxi S, Krishnan S, Jayaraj R. Prognostic Value of MicroRNAs in Stage II Colorectal Cancer Patients: A Systematic Review and Meta-Analysis. Mol Diagn Ther 2021; 24:15-30. [PMID: 32020560 DOI: 10.1007/s40291-019-00440-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
BACKGROUND We performed a systematic review and meta-analysis to identify and underline multiple microRNAs (miRNAs) as biomarkers of disease prognosis in stage II colorectal cancer (CRC) patients. METHODS AND ANALYSIS This systematic review and meta-analysis study was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The required articles were collected from online bibliographic databases from January 2011 to November 2019 with multiple permutation keywords. Quantitative data synthesis was based on a meta-analysis with pooled data to observe and analyse the outcome measures and effect estimates by using the random effect model. The subgroup analysis was performed from demographic characteristics and the available data. RESULTS Eighteen articles were included in this study, 16 of which were incorporated for meta-analysis to examine the stage II CRC prognosis with up- and downregulated miRNA expressions. The pooled hazard ratio (HR) for death in stage II CRC patients was 1.90 (95% confidence interval 1.63-2.211), with a significant p value. A subgroup analysis based on up- or downregulated miRNA expression individually and any deregulated miRNA was also associated with a worse prognosis. The subgroup analysis included parameters such as age, gender, stage II and III combined patients' survival and the repetitive miRNAs (miR21, miR215, miR143-5p, miR106a and miR145) individually. CONCLUSION MicroRNAs play a significant role in determining prognosis in stage II CRC patients, with upregulation of miR21, miR215, miR143-5p and miR106a, in particular, portending a worse prognosis. These miRNAs could be considered for further evaluation as biomarkers of prognosis and to guide the decision to administer adjuvant chemotherapy.
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Affiliation(s)
| | | | - Chellan Kumarasamy
- University of Adelaide, North Terrace Campus, Adelaide, SA, 5005, Australia
| | - Ajay Gupta
- American Oncology Institute, Nagpur, India
| | | | - Sunil Krishnan
- Department of Radiation Oncology, The University of Texas, Houston, TX, USA
| | - Rama Jayaraj
- College of Health and Human Sciences, Charles Darwin University, Ellengowan Drive, Darwin, NT, 0810, Australia.
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Maugeri A, Barchitta M, Magnano San Lio R, Li Destri G, Agodi A, Basile G. Epigenetic Aging and Colorectal Cancer: State of the Art and Perspectives for Future Research. Int J Mol Sci 2020; 22:ijms22010200. [PMID: 33379143 PMCID: PMC7795459 DOI: 10.3390/ijms22010200] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2020] [Revised: 12/22/2020] [Accepted: 12/24/2020] [Indexed: 12/13/2022] Open
Abstract
Although translational research has identified a large number of potential biomarkers involved in colorectal cancer (CRC) carcinogenesis, a better understanding of the molecular pathways associated with biological aging in colorectal cells and tissues is needed. Here, we aim to summarize the state of the art about the role of age acceleration, defined as the difference between epigenetic age and chronological age, in the development and progression of CRC. Some studies have shown that accelerated biological aging is positively associated with the risk of cancer and death in general. In line with these findings, other studies have shown how the assessment of epigenetic age in people at risk for CRC could be helpful for monitoring the molecular response to preventive interventions. Moreover, it would be interesting to investigate whether aberrant epigenetic aging could help identify CRC patients with a high risk of recurrence and a worst prognosis, as well as those who respond poorly to treatment. Yet, the application of this novel concept is still in its infancy, and further research should be encouraged in anticipation of future applications in clinical practice.
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Affiliation(s)
- Andrea Maugeri
- Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, via S. Sofia, 87, 95123 Catania, Italy; (A.M.); (R.M.S.L.); (G.L.D.); (A.A.)
| | - Martina Barchitta
- Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, via S. Sofia, 87, 95123 Catania, Italy; (A.M.); (R.M.S.L.); (G.L.D.); (A.A.)
- Correspondence:
| | - Roberta Magnano San Lio
- Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, via S. Sofia, 87, 95123 Catania, Italy; (A.M.); (R.M.S.L.); (G.L.D.); (A.A.)
| | - Giovanni Li Destri
- Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, via S. Sofia, 87, 95123 Catania, Italy; (A.M.); (R.M.S.L.); (G.L.D.); (A.A.)
| | - Antonella Agodi
- Department of Medical and Surgical Sciences and Advanced Technologies “GF Ingrassia”, University of Catania, via S. Sofia, 87, 95123 Catania, Italy; (A.M.); (R.M.S.L.); (G.L.D.); (A.A.)
| | - Guido Basile
- Department of General Surgery and Medical-Surgical Specialties, University of Catania, via S. Sofia, 78, 95123 Catania, Italy;
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Wu Z, Li Y, Zhang Y, Hu H, Wu T, Liu S, Chen W, Xie S, Lu Z. Colorectal Cancer Screening Methods and Molecular Markers for Early Detection. Technol Cancer Res Treat 2020; 19:1533033820980426. [PMID: 33353503 PMCID: PMC7768867 DOI: 10.1177/1533033820980426] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common malignant tumors in the digestive tract in humans. The development of colorectal cancer is composed of multiple stages, starting with benign adenomatous polyps in the inner wall of the large intestine and rectum, and then gradually developing. Then it developed into advanced adenomas carcinoma in situ and invasive carcinoma. Represents the distant metastasis of the most advanced development. The purpose of this review is to novel routine screening and diagnostic methods (e.g., Endoscopy and CT colonoscopy, SEPT9 methylation assay, Fecal test) and find reliable molecular markers for early diagnosis of CRC.
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Affiliation(s)
- Ziwei Wu
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, 12443Huazhong University of Science and Technology, Wuhan, China.,School of Laboratory Medicine, Hubei University of Traditional Chinese Medicine, Wuhan, China
| | - You Li
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, 12443Huazhong University of Science and Technology, Wuhan, China.,School of Laboratory Medicine, Hubei University of Traditional Chinese Medicine, Wuhan, China
| | - Yibin Zhang
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, 12443Huazhong University of Science and Technology, Wuhan, China.,School of Laboratory Medicine, Hubei University of Traditional Chinese Medicine, Wuhan, China
| | - Hui Hu
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, 12443Huazhong University of Science and Technology, Wuhan, China
| | - Tangwei Wu
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, 12443Huazhong University of Science and Technology, Wuhan, China
| | - Shuiyi Liu
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, 12443Huazhong University of Science and Technology, Wuhan, China.,Cancer Research Institute of Wuhan, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Weiqun Chen
- Cancer Research Institute of Wuhan, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Shenggao Xie
- School of Laboratory Medicine, Hubei University of Traditional Chinese Medicine, Wuhan, China
| | - Zhongxin Lu
- Department of Medical Laboratory, the Central Hospital of Wuhan, Tongji Medical College, 12443Huazhong University of Science and Technology, Wuhan, China.,School of Laboratory Medicine, Hubei University of Traditional Chinese Medicine, Wuhan, China.,Cancer Research Institute of Wuhan, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
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Farouk S, Khairy A, Salem AM, Soliman AF, Bader El Din NG. Differential Expression of miR-21, miR-23a, and miR-27a, and Their Diagnostic Significance in Egyptian Colorectal Cancer Patients. Genet Test Mol Biomarkers 2020; 24:825-834. [PMID: 33290159 DOI: 10.1089/gtmb.2020.0184] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background: Colorectal cancer (CRC) rates are affected by genetics, ethnicity, and environmental factors; it is considered one of the most aggressive human malignancies with high mortality and morbidity rates worldwide due, in part, to its asymptomatic nature during the early stages of disease. Objective: Owing to the impact of microRNA (miRNA) dysregulation on CRC development and progression, this study was conducted to explore the expression levels of mir-21, -23a, and -27a in the sera and tissues of Egyptian CRC patients and to evaluate their diagnostic efficacy based on circulating levels. Methods: In the test phase, the relative expression levels of the studied miRNAs were evaluated in the sera of 70 participants (35 CRC patients and 35 healthy controls) using quantitative real-time-polymerase chain reaction and to verify their diagnostic value. The exploratory phase was designed to validate the tumor-derived trait by comparing the miRNA levels in the cancerous and adjacent noncancerous tissues. Results: The relative expression levels of the studied miRNAs were significantly upregulated in both serum and tumor tissues of the patients compared to their corresponding controls. In addition, significant positive correlations were found between the relative expression levels of the studied miRNAs in serum samples and their levels in the matched CRC tissues. The serum expression levels of mir-21 and -23a were more predictive of CRC than mir-27a. Conclusion: Circulating mir-21, -23a, and -27a expression levels appear to be valuable diagnostic biomarkers for CRC, especially when combined.
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Affiliation(s)
- Sally Farouk
- Microbial Biotechnology Department, National Research Centre, Giza, Egypt
| | - Ahmed Khairy
- Endemic Medicine Department, Kasr Elainy Hospitals, Cairo University, Giza, Egypt
| | - Ahmed M Salem
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
| | - Ahmed F Soliman
- Biochemistry Department, Faculty of Science, Ain Shams University, Cairo, Egypt
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Cancer-Associated Stemness and Epithelial-to-Mesenchymal Transition Signatures Related to Breast Invasive Carcinoma Prognostic. Cancers (Basel) 2020; 12:cancers12103053. [PMID: 33092068 PMCID: PMC7589570 DOI: 10.3390/cancers12103053] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2020] [Revised: 10/12/2020] [Accepted: 10/16/2020] [Indexed: 02/06/2023] Open
Abstract
Simple Summary Breast cancer is one of the most common oncological diseases in women, as its incidence is rapidly growing. In this study, we have investigated the mechanism of epithelial-to-mesenchymal transition (EMT) and cancer stem cells (CSCs), demonstrating presence of an interconnectedness between them. This interconnectedness plays important roles in patient prognostic, as well as in diagnostic and therapeutic targets. It is identified that there is a common signature between CSCs and EMT, and this is represented by ALDH1A1, SFRP1, miR-139, miR-21, and miR-200c. This finding will provide a better understanding of this mechanism, and will facilitate the development of novel treatment options. Abstract Breast cancer is one of the most common oncological diseases in women, as its incidence is rapidly growing, rendering it unpredictable and causing more harm than ever before on an annual basis. Alterations of coding and noncoding genes are related to tumorigenesis and breast cancer progression. In this study, several key genes associated with epithelial-to-mesenchymal transition (EMT) and cancer stem cell (CSC) features were identified. EMT and CSCs are two key mechanisms responsible for self-renewal, differentiation, and self-protection, thus contributing to drug resistance. Therefore, understanding of the relationship between these processes may identify a therapeutic vulnerability that can be further exploited in clinical practice, and evaluate its correlation with overall survival rate. To determine expression levels of altered coding and noncoding genes, The Cancer Omics Atlas (TCOA) are used, and these data are overlapped with a list of CSCs and EMT-specific genes downloaded from NCBI. As a result, it is observed that CSCs are reciprocally related to EMT, thus identifying common signatures that allow for predicting the overall survival for breast cancer genes (BRCA). In fact, common CSCs and EMT signatures, represented by ALDH1A1, SFRP1, miR-139, miR-21, and miR-200c, are deemed useful as prognostic biomarkers for BRCA. Therefore, by mapping changes in gene expression across CSCs and EMT, suggesting a cross-talk between these two processes, we have been able to identify either the most common or specific genes or miRNA markers associated with overall survival rate. Thus, a better understanding of these mechanisms will lead to more effective treatment options.
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The Clinical Impact of MicroRNA-21 in Low Rectal Cancer Treated with High-Dose Chemoradiotherapy in the Organ Preserving Setting. GASTROINTESTINAL DISORDERS 2020. [DOI: 10.3390/gidisord2040034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Background: Organ preservation in the treatment of rectal cancer has seen an increase in interest. Clinical complete response (cCR) after high-dose chemoradiotherapy (CRT) allows for non-surgical management (NSM), but the selection of patients is challenging and standard clinical staging insufficient. MicroRNA-21-5p (miR-21) is ubiquitously upregulated in cancer and has been associated with treatment response in rectal cancer treated with standard preoperative CRT. The aim of the present study was to investigate this association in low rectal cancer treated in the NSM setting. Methods: Forty-eight patients from our single-arm phase II trial (NCT00952926) were eligible for analysis. All patients had resectable T2 or T3, N0–N1 low adenocarcinoma and received intensity-modulated radiotherapy plus brachytherapy boost and oral tegafur–uracil. Patients with cCR six weeks after end of treatment assessed by clinical examination, magnetic resonance imaging, and biopsy, were referred to observation and close follow-up. The miR expression in the diagnostic biopsies was measured by qPCR. The relationship between miR-21 expression and cCR was assessed using the Wilcoxon rank-sum test. Results: Thirty-eight patients had cCR after treatment and were allocated to observation while 10 patients had incomplete response and underwent surgery. MicroRNA-21 was successfully analyzed in all samples. The median tumor expression of miR-21 was significantly higher in patients with incomplete response than in those with cCR, 24.3 (95% confidence interval (CI) 17.1–36.8) and 16.6 (95% CI 13.9–21.1), respectively, p = 0.03. Conclusions: The present study adds to the evidence of the clinical impact of miR-21 in rectal cancer treated with CRT. The findings are comparable with results seen in patients treated in the standard preoperative setting and may assist in the selection of patients for an organ preserving approach.
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Ourô S, Mourato C, Ferreira MP, Albergaria D, Cardador A, Castro RE, Maio R, Rodrigues CMP. Evaluation of Tissue and Circulating miR-21 as Potential Biomarker of Response to Chemoradiotherapy in Rectal Cancer. Pharmaceuticals (Basel) 2020; 13:E246. [PMID: 32937907 PMCID: PMC7559906 DOI: 10.3390/ph13090246] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2020] [Revised: 09/10/2020] [Accepted: 09/12/2020] [Indexed: 11/17/2022] Open
Abstract
Response to chemoradiotherapy (CRT) in patients with locally advanced rectal cancer (RC) is quite variable and it is urgent to find predictive biomarkers of response. We investigated miR-21 as tissue and plasma biomarker of response to CRT in a prospective cohort of RC patients; The expression of miR-21 was analyzed in pre- and post-CRT rectal tissue and plasma in 37 patients with RC. Two groups were defined: Pathological responders (TRG 0, 1 and 2) and non-responders (TRG 3). The association between miR-21, clinical and oncological outcomes was assessed; miR-21 was upregulated in tumor tissue and we found increased odds of overexpression in pre-CRT tumor tissue (OR: 1.63; 95% CI: 0.40-6.63, p = 0.498) and pre-CRT plasma (OR: 1.79; 95% CI: 0.45-7.19, p = 0.414) of non-responders. The overall recurrence risk increased with miR-21 overexpression in pre-CRT tumor tissue (HR: 2.175, p = 0.37); Significantly higher miR-21 expression is observed in tumor tissue comparing with non-neoplastic. Increased odds of non-response is reported in patients expressing higher miR-21, although without statistical significance. This is one of the first studies on circulating miR-21 as a potential biomarker of response to CRT in RC patients.
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Affiliation(s)
- Susana Ourô
- Surgical Department, Hospital Beatriz Ângelo, 2674-514 Loures, Portugal; (M.P.F.); (D.A.); (R.M.)
- NOVA Medical School, Faculdade de Ciências Médicas, 1169-056 Lisboa, Portugal
| | - Cláudia Mourato
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal; (C.M.); (A.C.); (R.E.C.)
| | - Marisa P. Ferreira
- Surgical Department, Hospital Beatriz Ângelo, 2674-514 Loures, Portugal; (M.P.F.); (D.A.); (R.M.)
| | - Diogo Albergaria
- Surgical Department, Hospital Beatriz Ângelo, 2674-514 Loures, Portugal; (M.P.F.); (D.A.); (R.M.)
| | - André Cardador
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal; (C.M.); (A.C.); (R.E.C.)
| | - Rui E. Castro
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal; (C.M.); (A.C.); (R.E.C.)
| | - Rui Maio
- Surgical Department, Hospital Beatriz Ângelo, 2674-514 Loures, Portugal; (M.P.F.); (D.A.); (R.M.)
- NOVA Medical School, Faculdade de Ciências Médicas, 1169-056 Lisboa, Portugal
| | - Cecília M. P. Rodrigues
- Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisboa, Portugal; (C.M.); (A.C.); (R.E.C.)
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50
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Ahadi A. The significance of microRNA deregulation in colorectal cancer development and the clinical uses as a diagnostic and prognostic biomarker and therapeutic agent. Noncoding RNA Res 2020; 5:125-134. [PMID: 32954092 PMCID: PMC7476809 DOI: 10.1016/j.ncrna.2020.08.003] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Revised: 08/19/2020] [Accepted: 08/19/2020] [Indexed: 12/14/2022] Open
Abstract
Colorectal cancer (CRC) is one of the most widely recognized and deadly malignancies worldwide. Although death rates have declined over the previous decade, mainly because of enhanced screening or potential treatment alternatives, CRC remains the third leading cause of cancer-related mortality globally, with an estimated incidence of over 1 million new cases and approximately 600 000 deaths estimated yearly. Therefore, many scientific efforts are put into the development of new diagnostic biomarkers for CRC. MicroRNAs (miRNAs), one of the epigenetics categories, have demonstrated significant roles in carcinogenesis and progression through regulating epithelial-mesenchymal transition (EMT), oncogenic signaling pathways, and metastasis. Dysregulation of miRNAs expression has been reported in many cancers, including CRC. The expression profile of miRNAs is reproducibly altered in CRC, and their expression patterns are associated with diagnosis, prognosis, and therapeutic outcomes in CRC. Recently, many studies were conducted on the dysregulation of miRNAs as a diagnostic and prognostic biomarker in CRC. Among them, some miRNAs, which include miR-21, miR-34 family, miR-155, miR-224, and miR-378, have been more studied in CRC with more prominent roles in diagnosis, prognosis, and therapy. In the present review, we summarized the latest information regarding the dysregulated miRNAs in CRC and the advantages of using miRNAs as a biomarker for CRC diagnosis, treatment, and their function in different signaling pathways involved in CRC progression. Moreover, we described the translation of miRNA research to potential therapeutic applications in the management of CRC in clinical settings.
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Affiliation(s)
- Alireza Ahadi
- Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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