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Chong Y, Zhou H, Zhang P, Xue L, Du Q, Chong T, Wang Z. Establishing cM0 (i+) stage criteria in localized renal cell carcinoma based on postoperative circulating tumor cells monitoring. BMC Cancer 2025; 25:436. [PMID: 40069681 PMCID: PMC11895218 DOI: 10.1186/s12885-025-13815-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 02/25/2025] [Indexed: 03/15/2025] Open
Abstract
BACKGROUND The diagnostic criteria for cM0 (i+) stage proposed by American Joint Committee on Cancer (AJCC) in renal cell carcinoma (RCC) still remains unclear. The present study aimed to establish and validate the criteria of cM0 (i+) stage based on postoperative circulating tumor cells (CTCs) monitoring in patients with localized renal cell carcinoma (LRCC). MATERIALS AND METHODS This study enrolled 204 patients with LRCC who received partial or radical nephrectomy from January 2015 to November 2021. Cases were randomly divided into test set and validation set. The correlation between clinicopathological features and CTCs counts were analyzed and prognostic variables were determined by Lasso regression. Receiver operating characteristic curve of the prognosis-related CTCs terms were plotted to determine their optimal cut-off value to establish the criteria of cM0 (i+) stage. Its clinical prognostic significance was explored by Kaplan-Meier analysis and Log-rank test. The above analysis was conducted by SPSS26.0 software and R Studio software. P < 0.05 was considered to be statistically significant. RESULTS A total of 204 patients were analyzed in this study.There were no significant differences in variables between the validation and test sets (P>0.05). Total CTCs, mesenchymal CTCs (MCTCs), and CTCs showing a progressive trend were selected as the diagnostic basis for the cM0 (i+) stage through correlation analysis and Lasso regression. The cM0 (i+) stage identified patients meeting the following criteria simultaneously: (1) total CTCs ≥ 6; (2) MCTCs ≥ 1; and (3) a demonstrated trend of progression in either total CTCs or MCTCs. In the validation group, Kaplan-Meier analysis showed that patients with cM0 (i+) stage had significantly shorter progression-free survival than the control group(P<0.05). The results of multivariate Cox regression analysis also showed cM0 (i+) was an independent risk factor for postoperative progression of LRCC patients [12.448 (1.874-82.666) P < 0.05]. Its 1-3 years' prediction discrimination is better than that of UISS score and SSIGN score, which was also verified in the validation set. CONCLUSION The study proposed a diagnostic criterion for M0 (i+) stage in LRCC based on postoperative CTCs monitoring. It was identified as an independent risk factor for postoperative progression and demonstrated potential advantages over the UISS and SSIGN scores in internal validation.
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Affiliation(s)
- Yue Chong
- Department of Urology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi Wu Road, Xin Cheng district, Xi'an, Shaanxi, 710004, China
| | - Haibin Zhou
- Department of Urology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi Wu Road, Xin Cheng district, Xi'an, Shaanxi, 710004, China
- Department of Urology, First Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi, 710077, China
| | - Peng Zhang
- Department of Urology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi Wu Road, Xin Cheng district, Xi'an, Shaanxi, 710004, China
| | - Li Xue
- Department of Urology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi Wu Road, Xin Cheng district, Xi'an, Shaanxi, 710004, China
| | - Qiao Du
- Department of Urology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi Wu Road, Xin Cheng district, Xi'an, Shaanxi, 710004, China
- Baoji People's Hospital, Baoji, 721001, Shaanxi, China
| | - Tie Chong
- Department of Urology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi Wu Road, Xin Cheng district, Xi'an, Shaanxi, 710004, China
| | - Zhenlong Wang
- Department of Urology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi Wu Road, Xin Cheng district, Xi'an, Shaanxi, 710004, China.
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Rao J, Wang X, Wan X, Chen C, Xiong X, Xiong A, Yang Z, Chen L, Wang T, Mao L, Jiang C, Zeng J, Zheng Z. Multiomics Approach Identifies Key Proteins and Regulatory Pathways in Colorectal Cancer. J Proteome Res 2025; 24:356-367. [PMID: 39699012 DOI: 10.1021/acs.jproteome.4c00902] [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: 12/20/2024]
Abstract
The prevalence rate of colorectal cancer (CRC) has dramatically increased in recent decades. However, robust CRC biomarkers with therapeutic value for early diagnosis are still lacking. To comprehensively reveal the molecular characteristics of CRC development, we employed a multiomics strategy to investigate eight different types of CRC samples. Proteomic analysis revealed 2022 and 599 differentially expressed tissue proteins between CRC and control groups in CRC patients and CRC mice, respectively. In patients with colorectal precancerous lesions, 25 and 34 significantly changed proteins were found between patients and healthy controls in plasma and white blood cells, respectively. Notably, vesicle-associated membrane protein-associated protein A (VAPA) was found to be consistently and significantly decreased in most types of CRC samples, and its level was also significantly correlated with increased overall survival of CRC patients. Furthermore, 37 significantly enriched pathways in CRC were further validated via metabolomics analysis. Ten VAPA-related pathways were found to be significantly enriched in CRC samples, among which PI3K-Akt signaling, central carbon metabolism in cancer, cholesterol metabolism, and ABC transporter pathways were also enriched in the premalignant stage. Our study identified VAPA and its associated pathways as key regulators, suggesting their potential applications in the early diagnosis and prognosis of CRC.
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Affiliation(s)
- Jun Rao
- The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Cancer Institute, Jiangxi Cancer Hospital, Nanchang 330029, Jiangxi Province, China
| | - Xing Wang
- The First Affiliated Hospital of Nanchang Medical College, Jiangxi Provincial People's Hospital, Nanchang 330006, Jiangxi Province, China
| | - Xianghui Wan
- The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Cancer Institute, Jiangxi Cancer Hospital, Nanchang 330029, Jiangxi Province, China
| | - Chao Chen
- The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Cancer Institute, Jiangxi Cancer Hospital, Nanchang 330029, Jiangxi Province, China
| | - Xiaopeng Xiong
- The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Cancer Institute, Jiangxi Cancer Hospital, Nanchang 330029, Jiangxi Province, China
| | - Aihua Xiong
- The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Cancer Institute, Jiangxi Cancer Hospital, Nanchang 330029, Jiangxi Province, China
| | - Zhiqing Yang
- The Second Clinical Medical College, Shaanxi University of Chinese Medicine, Xian 710000, Shaanxi Province, China
| | - Lanyu Chen
- The First Affiliated Hospital of Nanchang Medical College, Jiangxi Provincial People's Hospital, Nanchang 330006, Jiangxi Province, China
| | - Ting Wang
- The First Affiliated Hospital of Nanchang Medical College, Jiangxi Provincial People's Hospital, Nanchang 330006, Jiangxi Province, China
| | - Lihua Mao
- The First Affiliated Hospital of Nanchang Medical College, Jiangxi Provincial People's Hospital, Nanchang 330006, Jiangxi Province, China
| | - Chunling Jiang
- Department of Radiation Oncology, Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital, Nanchang 330029, China
| | - Jiquan Zeng
- The Second Affiliated Hospital of Nanchang Medical College, Jiangxi Cancer Institute, Jiangxi Cancer Hospital, Nanchang 330029, Jiangxi Province, China
| | - Zhi Zheng
- The First Affiliated Hospital of Nanchang Medical College, Jiangxi Provincial People's Hospital, Nanchang 330006, Jiangxi Province, China
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Dong X, Zhang K, Yi S, Wang L, Wang X, Li M, Liang S, Wang Y, Zeng Y. Multi-omics profiling combined with molecular docking reveals immune-inflammatory proteins as potential drug targets in colorectal cancer. Biochem Biophys Res Commun 2024; 739:150598. [PMID: 39213754 DOI: 10.1016/j.bbrc.2024.150598] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2024] [Revised: 08/20/2024] [Accepted: 08/22/2024] [Indexed: 09/04/2024]
Abstract
Colorectal cancer is globally ranked as the third most common malignant tumor. Its development involves a complex biological process driven by various genetic and epigenetic alterations. To elucidate the biological significance of the extensive omics data, we conducted comparative multi-omics studies on colorectal cancer patients at different clinical stages. Bioinformatics methods were applied to analyze multi-omics datasets and explore the molecular landscape. Drug prediction and molecular docking also were conducted to assess potential therapeutic interventions. In vitro experiments were used to validate the inhibitory effect on the migration and proliferation of cell lines. The results indicate up-regulated proteins involved in immune-inflammatory related pathways, while biomarkers related to muscular contraction and cell adhesion are significantly down-regulated. Drug prediction, coupled with in vitro experiments, suggests that AZ-628 may act as a potential drug to inhibit the proliferation and migration of CRC cell lines HCT-116 and HT-29 by regulating the aforementioned key biological pathways or proteins. Complementing these findings, metabolomics analysis unveiled a down-regulation of key carbon metabolism pathways, alongside an up-regulation in amino acid metabolism, particularly proline metabolism. This metabolic shift may reflect an adaptive response in cancer cells, favoring specific amino acids to support their growth. Together, these integrated results provide valuable insights into the intricate landscape of tumor development, highlighting the crossroads of immune regulation, cellular structure, and metabolic reprogramming in the tumorigenic process and providing valuable insights into cancer pathology.
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Affiliation(s)
- Xiaoping Dong
- National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China; Peptide and Small Molecule Drug R&D Platform, Furong Laboratory, Hunan Normal University, Changsha, 410081, China
| | - Kun Zhang
- The State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha, 410081, Hunan, China
| | - Siwei Yi
- National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China; Peptide and Small Molecule Drug R&D Platform, Furong Laboratory, Hunan Normal University, Changsha, 410081, China
| | - Lingxiang Wang
- National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China; Peptide and Small Molecule Drug R&D Platform, Furong Laboratory, Hunan Normal University, Changsha, 410081, China; The State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha, 410081, Hunan, China
| | - Xingyao Wang
- National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China; Peptide and Small Molecule Drug R&D Platform, Furong Laboratory, Hunan Normal University, Changsha, 410081, China
| | - Mengtuo Li
- National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China; Peptide and Small Molecule Drug R&D Platform, Furong Laboratory, Hunan Normal University, Changsha, 410081, China
| | - Songping Liang
- National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China; Peptide and Small Molecule Drug R&D Platform, Furong Laboratory, Hunan Normal University, Changsha, 410081, China
| | - YongJun Wang
- Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China.
| | - Yong Zeng
- National & Local Joint Engineering Laboratory of Animal Peptide Drug Development, College of Life Sciences, Hunan Normal University, Changsha, Hunan, China; Peptide and Small Molecule Drug R&D Platform, Furong Laboratory, Hunan Normal University, Changsha, 410081, China; The State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha, 410081, Hunan, China.
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Yun Y, Kim S, Lee SN, Cho HY, Choi JW. Nanomaterial-based detection of circulating tumor cells and circulating cancer stem cells for cancer immunotherapy. NANO CONVERGENCE 2024; 11:56. [PMID: 39671082 PMCID: PMC11645384 DOI: 10.1186/s40580-024-00466-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/29/2024] [Accepted: 12/04/2024] [Indexed: 12/14/2024]
Abstract
Nanomaterials have emerged as transformative tools for detecting circulating tumor cells (CTCs) and circulating cancer stem cells (CCSCs), significantly enhancing cancer diagnostics and immunotherapy. Nanomaterials, including those composed of gold, magnetic materials, and silica, have enhanced the sensitivity, specificity, and efficiency of isolating these rare cells from blood. These developments are of paramount importance for the early detection of cancer and for providing real-time insights into metastasis and treatment resistance, which are essential for the development of personalized immunotherapies. The combination of nanomaterial-based platforms with phenotyping techniques, such as Raman spectroscopy and microfluidics, enables researchers to enhance immunotherapy protocols targeting specific CTC and CCSC markers. Nanomaterials also facilitate the targeted delivery of immunotherapeutic agents, including immune checkpoint inhibitors and therapeutic antibodies, directly to tumor cells. This synergistic approach has the potential to enhance therapeutic efficacy and mitigate the risk of metastasis and relapse. In conclusion, this review critically examines the use of nanomaterial-driven detection systems for detecting CTCs and CCSCs, their application in immunotherapy, and suggests future directions, highlighting their potential to transform the integration of diagnostics and treatment, thereby paving the way for more precise and personalized cancer therapies.
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Affiliation(s)
- Yeochan Yun
- Department of Bio and Fermentation Convergence Technology, Kookmin University, 77 Jeongneung-ro, Seongbuk-gu, Seoul, 02707, Republic of Korea
| | - Seewoo Kim
- Department of Chemical and Biomolecular Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul, 04107, Republic of Korea
| | - Sang-Nam Lee
- Uniance Gene Inc., 273, Digital-ro, Guro-gu, Seoul, 08381, Republic of Korea.
| | - Hyeon-Yeol Cho
- Department of Bio and Fermentation Convergence Technology, Kookmin University, 77 Jeongneung-ro, Seongbuk-gu, Seoul, 02707, Republic of Korea.
| | - Jeong-Woo Choi
- Department of Chemical and Biomolecular Engineering, Sogang University, 35 Baekbeom-ro, Mapo-gu, Seoul, 04107, Republic of Korea.
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Liu Z, Zhou Y, Lu J, Gong T, Ibáñez E, Cifuentes A, Lu W. Microfluidic biosensors for biomarker detection in body fluids: a key approach for early cancer diagnosis. Biomark Res 2024; 12:153. [PMID: 39639411 PMCID: PMC11622463 DOI: 10.1186/s40364-024-00697-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Accepted: 11/22/2024] [Indexed: 12/07/2024] Open
Abstract
Early detection of cancer significantly improves patient outcomes, with biomarkers offering a promising avenue for earlier and more precise diagnoses. Microfluidic biosensors have emerged as a powerful tool for detecting these biomarkers in body fluids, providing enhanced sensitivity, specificity, and rapid analysis. This review focuses on recent advances in microfluidic biosensors from 2018 to 2024, detailing their operational principles, fabrication techniques, and integration with nanotechnology for cancer biomarker detection. Additionally, we have reviewed recent innovations in several aspects of microfluidic biosensors, such as novel detection technologies, nanomaterials and novel microfluidic chip structures, which significantly enhance detection capabilities. We highlight key biomarkers pertinent to early cancer detection and explore how these innovations in biosensor technology contribute to the evolving landscape of personalized medicine. We further explore how these technologies could be incorporated into clinical cancer diagnostic workflows to improve early detection and treatment outcomes. These innovations could help enable more precise and personalized cancer diagnostics. In addition, this review addresses several important issues such as enhancing the scalability and sensitivity of these biosensors in clinical settings and points out future possibilities of combining artificial intelligence diagnostics with microfluidic biosensors to optimize their practical applications. This overview aims to guide future research and clinical applications by addressing current challenges and identifying opportunities for further development in the field of biomarker research.
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Affiliation(s)
- Zhiting Liu
- School of Medicine and Health, Harbin Institute of Technology, 92 Xidazhi Street, Nangang District, Harbin, 150001, China
- National and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, 92 Xidazhi Street, Nangang District, Harbin, 150001, China
| | - Yingyu Zhou
- School of Medicine and Health, Harbin Institute of Technology, 92 Xidazhi Street, Nangang District, Harbin, 150001, China.
- Zhengzhou Research Institute, Harbin Institute of Technology, Zhengzhou, Henan, China.
- National and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, 92 Xidazhi Street, Nangang District, Harbin, 150001, China.
| | - Jia Lu
- School of Mechatronics Engineering, Harbin Institute of Technology, 92 Xidazhi Street, Nangang District, Harbin, 150001, China.
- Zhengzhou Research Institute, Harbin Institute of Technology, Zhengzhou, Henan, China.
| | - Ting Gong
- School of Medicine and Health, Harbin Institute of Technology, 92 Xidazhi Street, Nangang District, Harbin, 150001, China
- National and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, 92 Xidazhi Street, Nangang District, Harbin, 150001, China
| | - Elena Ibáñez
- Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera 9, Madrid, 28049, Spain
| | - Alejandro Cifuentes
- Laboratory of Foodomics, Institute of Food Science Research, CIAL, CSIC, Nicolás Cabrera 9, Madrid, 28049, Spain
| | - Weihong Lu
- School of Medicine and Health, Harbin Institute of Technology, 92 Xidazhi Street, Nangang District, Harbin, 150001, China.
- Zhengzhou Research Institute, Harbin Institute of Technology, Zhengzhou, Henan, China.
- National and Local Joint Engineering Laboratory for Synthesis Transformation and Separation of Extreme Environmental Nutrients, 92 Xidazhi Street, Nangang District, Harbin, 150001, China.
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Coskun A, Ertaylan G, Pusparum M, Van Hoof R, Kaya ZZ, Khosravi A, Zarrabi A. Advancing personalized medicine: Integrating statistical algorithms with omics and nano-omics for enhanced diagnostic accuracy and treatment efficacy. Biochim Biophys Acta Mol Basis Dis 2024; 1870:167339. [PMID: 38986819 DOI: 10.1016/j.bbadis.2024.167339] [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: 04/04/2024] [Revised: 06/25/2024] [Accepted: 07/03/2024] [Indexed: 07/12/2024]
Abstract
Medical laboratory services enable precise measurement of thousands of biomolecules and have become an inseparable part of high-quality healthcare services, exerting a profound influence on global health outcomes. The integration of omics technologies into laboratory medicine has transformed healthcare, enabling personalized treatments and interventions based on individuals' distinct genetic and metabolic profiles. Interpreting laboratory data relies on reliable reference values. Presently, population-derived references are used for individuals, risking misinterpretation due to population heterogeneity, and leading to medical errors. Thus, personalized references are crucial for precise interpretation of individual laboratory results, and the interpretation of omics data should be based on individualized reference values. We reviewed recent advancements in personalized laboratory medicine, focusing on personalized omics, and discussed strategies for implementing personalized statistical approaches in omics technologies to improve global health and concluded that personalized statistical algorithms for interpretation of omics data have great potential to enhance global health. Finally, we demonstrated that the convergence of nanotechnology and omics sciences is transforming personalized laboratory medicine by providing unparalleled diagnostic precision and innovative therapeutic strategies.
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Affiliation(s)
- Abdurrahman Coskun
- Acibadem University, School of Medicine, Department of Medical Biochemistry, Istanbul, Turkey.
| | - Gökhan Ertaylan
- Unit Health, Environmental Intelligence, Flemish Institute for Technological Research (VITO), Mol 2400, Belgium
| | - Murih Pusparum
- Unit Health, Environmental Intelligence, Flemish Institute for Technological Research (VITO), Mol 2400, Belgium; I-Biostat, Data Science Institute, Hasselt University, Hasselt 3500, Belgium
| | - Rebekka Van Hoof
- Unit Health, Environmental Intelligence, Flemish Institute for Technological Research (VITO), Mol 2400, Belgium
| | - Zelal Zuhal Kaya
- Nisantasi University, School of Medicine, Department of Medical Biochemistry, Istanbul, Turkey
| | - Arezoo Khosravi
- Department of Genetics and Bioengineering, Faculty of Engineering and Natural Sciences, Istanbul Okan University, Istanbul 34959, Turkey
| | - Ali Zarrabi
- Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul 34396, Turkey; Graduate School of Biotehnology and Bioengeneering, Yuan Ze University, Taoyuan 320315, Taiwan; Department of Research Analytics, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600 077, India
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Portella L, Bertolini G, Guardascione G, Di Febbraro DG, Ieranò C, D'Alterio C, Rea G, Napolitano M, Santagata S, Trotta AM, Camerlingo R, Scarpa E, Cecere SC, Ottaiano A, Palumbo G, Morabito A, Somma T, De Rosa G, Mayol L, Pacelli R, Pignata S, Scala S. CXCL12-loaded-hydrogel (CLG): A new device for metastatic circulating tumor cells (CTCs) capturing and characterization. Heliyon 2024; 10:e35524. [PMID: 39170328 PMCID: PMC11336720 DOI: 10.1016/j.heliyon.2024.e35524] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2023] [Revised: 07/29/2024] [Accepted: 07/30/2024] [Indexed: 08/23/2024] Open
Abstract
Background Circulating Tumor Cells (CTCs) represent a small, heterogeneous population that comprise the minority of cells able to develop metastasis. To trap and characterize CTCs with metastatic attitude, a CXCL12-loaded hyaluronic-gel (CLG) was developed. CXCR4+cells with invasive capability would infiltrate CLG. Methods Human colon, renal, lung and ovarian cancer cells (HT29, A498, H460 and OVCAR8 respectively) were seeded on 150 μl Empty Gels (EG) or 300 ng/ml CXCL12 loaded gel (CLG) and allowed to infiltrate for 16 h. Gels were then digested and fixed with 2 % FA-HAse for human cancer cell enumeration or digested with HAse and cancer cells recovered. CLG-recovered cells migrated toward CXCL12 and were tested for colonies/spheres formation. Moreover, CXCR4, E-Cadherin and Vimentin expression was assessed through flow cytometry and RT-PCR. The clinical trial "TRAP4MET" recruited 48 metastatic/advanced cancer patients (8 OC, 8 LC, 8 GBM, 8 EC, 8 RCC and 8 EC). 10 cc whole blood were devoted to PBMCs extraction (7 cc) and ScreenCell™ filters (3 cc) CTCs evaluation. Ficoll-isolated patient's PBMCs were seeded over CLG and allowed to infiltrate for 16 h; gels were digested and fixed with 2 % FA-HAse, cells stained and DAPI+/CD45-/pan-CK + cells enumerated as CTCs. Results Human cancer cells infiltrate CLG more efficiently than EG (CLG/EG ratio 1.25 for HT29/1.58 for A498/1.71 for H460 and 2.83 for OVCAR8). CLG-recovered HT29 cells display hybrid-mesenchymal features [low E-cadherin (40 %) and high vimentin (235 %) as compared to HT29], CXCR4 two-fold higher than HT29, efficiently migrate toward CXCL12 (two-fold higher than HT29) and developed higher number of colonies (171 ± 21 for HT29-CLG vs 131 ± 8 colonies for HT29)/larger spheres (spheroid area: 26561 ± 6142 μm2 for HT29-CLG vs 20297 ± 7238 for HT29). In TRAP4MET clinical trial, CLG-CTCs were isolated in 8/8 patients with OC, 6/8 with LC, 6/8 with CRC, 8/8 with EC, 8/8 with RCC cancer and 5/8 with GBM. Interestingly, in OC, LC and GBM, CLG isolated higher number of CTCs as compared to the conventional ScreenCell™ (CLG/SC ratio = 1.88 for OC, 2.47 for LC and 11.89 for GBM). Bland and Altman blot analysis and Passing and Bablok regression analysis showed concordance between the methodological approaches but indicate that SC and CLG are not superimposable suggesting that the two systems select cells with different features. Conclusion CLG might represent a new and easy tool to isolate invasive CTCs in multiple cancers such as OC, LC and GBM at today orphan of reliable methods to consistently detect CTCs.
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Affiliation(s)
- Luigi Portella
- Microenvironment Molecular Targets, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
| | - Giulia Bertolini
- Tumor Genomic Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
| | - Giuseppe Guardascione
- Microenvironment Molecular Targets, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
| | - Dario Guido Di Febbraro
- Microenvironment Molecular Targets, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
| | - Caterina Ieranò
- Microenvironment Molecular Targets, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
| | - Crescenzo D'Alterio
- Microenvironment Molecular Targets, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
| | - Giuseppina Rea
- Microenvironment Molecular Targets, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
| | - Maria Napolitano
- Microenvironment Molecular Targets, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
| | - Sara Santagata
- Microenvironment Molecular Targets, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
| | - Anna Maria Trotta
- Microenvironment Molecular Targets, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
| | - Rosa Camerlingo
- Cell Biology and Biotherapy, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
| | - Emilia Scarpa
- Gynecology Oncology, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
| | - Sabrina Chiara Cecere
- Gynecology Oncology, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
| | - Alessandro Ottaiano
- Abdominal Oncology, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
| | - Giuliano Palumbo
- Thoracic Medical Oncology, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
| | - Alessandro Morabito
- Thoracic Medical Oncology, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
| | - Teresa Somma
- Department of Neurosciences, University of Naples Federico II, Italy
| | | | - Laura Mayol
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Italy
| | - Roberto Pacelli
- Department of Advanced Biomedical Sciences, University of Naples Federico II, Italy
| | - Sandro Pignata
- Gynecology Oncology, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
| | - Stefania Scala
- Microenvironment Molecular Targets, Istituto Nazionale Tumori IRCCS - Fondazione G Pascale, Napoli, Italy
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da Silva TF, de Azevedo JC, Teixeira EB, Casseb SMM, Moreira FC, de Assumpção PP, dos Santos SEB, Calcagno DQ. From haystack to high precision: advanced sequencing methods to unraveling circulating tumor DNA mutations. Front Mol Biosci 2024; 11:1423470. [PMID: 39165643 PMCID: PMC11333322 DOI: 10.3389/fmolb.2024.1423470] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2024] [Accepted: 07/11/2024] [Indexed: 08/22/2024] Open
Abstract
Identifying mutations in cancer-associated genes to guide patient treatments is essential for precision medicine. Circulating tumor DNA (ctDNA) offers valuable insights for early cancer detection, treatment assessment, and surveillance. However, a key issue in ctDNA analysis from the bloodstream is the choice of a technique with adequate sensitivity to identify low frequent molecular changes. Next-generation sequencing (NGS) technology, evolving from parallel to long-read capabilities, enhances ctDNA mutation analysis. In the present review, we describe different NGS approaches for identifying ctDNA mutation, discussing challenges to standardized methodologies, cost, specificity, clinical context, and bioinformatics expertise for optimal NGS application.
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Affiliation(s)
- Tamires Ferreira da Silva
- Programa de Residência Multiprofissional em Saúde (Oncologia), Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil
| | - Juscelino Carvalho de Azevedo
- Programa de Residência Multiprofissional em Saúde (Oncologia), Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil
| | | | | | | | | | | | - Danielle Queiroz Calcagno
- Programa de Residência Multiprofissional em Saúde (Oncologia), Hospital Universitário João de Barros Barreto, Universidade Federal do Pará, Belém, Brazil
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil
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9
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Dang Q, Zuo L, Hu X, Zhou Z, Chen S, Liu S, Ba Y, Zuo A, Xu H, Weng S, Zhang Y, Luo P, Cheng Q, Liu Z, Han X. Molecular subtypes of colorectal cancer in the era of precision oncotherapy: Current inspirations and future challenges. Cancer Med 2024; 13:e70041. [PMID: 39054866 PMCID: PMC11272957 DOI: 10.1002/cam4.70041] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2024] [Revised: 07/07/2024] [Accepted: 07/12/2024] [Indexed: 07/27/2024] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is among the most hackneyed malignancies. Even patients with identical clinical symptoms and the same TNM stage still exhibit radically different clinical outcomes after receiving equivalent treatment regimens, indicating extensive heterogeneity of CRC. Myriad molecular subtypes of CRC have been exploited for decades, including the most compelling consensus molecular subtype (CMS) classification that has been broadly applied for patient stratification and biomarker-drug combination formulation. Encountering barriers to clinical translation, however, CMS classification fails to fully reflect inter- or intra-tumor heterogeneity of CRC. As a consequence, addressing heterogeneity and precisely managing CRC patients with unique characteristics remain arduous tasks for clinicians. REVIEW In this review, we systematically summarize molecular subtypes of CRC and further elaborate on their clinical applications, limitations, and future orientations. CONCLUSION In recent years, exploration of subtypes through cell lines, animal models, patient-derived xenografts (PDXs), organoids, and clinical trials contributes to refining biological insights and unraveling subtype-specific therapies in CRC. Therapeutic interventions including nanotechnology, clustered regulatory interspaced short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9), gut microbiome, and liquid biopsy are powerful tools with the possibility to shift the immunologic landscape and outlook for CRC precise medicine.
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Affiliation(s)
- Qin Dang
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
- Department of Colorectal SurgeryThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Lulu Zuo
- Center for Reproductive MedicineThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Xinru Hu
- Department of Cardiology, West China HospitalSichuan UniversityChengduSichuanChina
| | - Zhaokai Zhou
- Department of UrologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Shuang Chen
- Center for Reproductive MedicineThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Shutong Liu
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Yuhao Ba
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Anning Zuo
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Hui Xu
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Siyuan Weng
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Yuyuan Zhang
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
| | - Peng Luo
- Department of Oncology, Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdongChina
| | - Quan Cheng
- Department of Neurosurgery, Xiangya HospitalCentral South UniversityChangshaHunanChina
| | - Zaoqu Liu
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
- Interventional Treatment and Clinical Research Center of Henan ProvinceZhengzhouHenanChina
- Interventional Institute of Zhengzhou UniversityZhengzhouHenanChina
- Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Xinwei Han
- Department of Interventional RadiologyThe First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina
- Interventional Treatment and Clinical Research Center of Henan ProvinceZhengzhouHenanChina
- Interventional Institute of Zhengzhou UniversityZhengzhouHenanChina
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10
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Kotsifaki A, Maroulaki S, Armakolas A. Exploring the Immunological Profile in Breast Cancer: Recent Advances in Diagnosis and Prognosis through Circulating Tumor Cells. Int J Mol Sci 2024; 25:4832. [PMID: 38732051 PMCID: PMC11084220 DOI: 10.3390/ijms25094832] [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: 03/15/2024] [Revised: 04/25/2024] [Accepted: 04/25/2024] [Indexed: 05/13/2024] Open
Abstract
This review offers a comprehensive exploration of the intricate immunological landscape of breast cancer (BC), focusing on recent advances in diagnosis and prognosis through the analysis of circulating tumor cells (CTCs). Positioned within the broader context of BC research, it underscores the pivotal role of the immune system in shaping the disease's progression. The primary objective of this investigation is to synthesize current knowledge on the immunological aspects of BC, with a particular emphasis on the diagnostic and prognostic potential offered by CTCs. This review adopts a thorough examination of the relevant literature, incorporating recent breakthroughs in the field. The methodology section succinctly outlines the approach, with a specific focus on CTC analysis and its implications for BC diagnosis and prognosis. Through this review, insights into the dynamic interplay between the immune system and BC are highlighted, with a specific emphasis on the role of CTCs in advancing diagnostic methodologies and refining prognostic assessments. Furthermore, this review presents objective and substantiated results, contributing to a deeper understanding of the immunological complexity in BC. In conclusion, this investigation underscores the significance of exploring the immunological profile of BC patients, providing valuable insights into novel advances in diagnosis and prognosis through the utilization of CTCs. The objective presentation of findings emphasizes the crucial role of the immune system in BC dynamics, thereby opening avenues for enhanced clinical management strategies.
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Affiliation(s)
| | | | - Athanasios Armakolas
- Physiology Laboratory, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece; (A.K.); (S.M.)
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11
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Díaz del Arco C, Fernández Aceñero MJ, Ortega Medina L. Liquid biopsy for gastric cancer: Techniques, applications, and future directions. World J Gastroenterol 2024; 30:1680-1705. [PMID: 38617733 PMCID: PMC11008373 DOI: 10.3748/wjg.v30.i12.1680] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/04/2023] [Revised: 02/01/2024] [Accepted: 03/08/2024] [Indexed: 03/28/2024] Open
Abstract
After the study of circulating tumor cells in blood through liquid biopsy (LB), this technique has evolved to encompass the analysis of multiple materials originating from the tumor, such as nucleic acids, extracellular vesicles, tumor-educated platelets, and other metabolites. Additionally, research has extended to include the examination of samples other than blood or plasma, such as saliva, gastric juice, urine, or stool. LB techniques are diverse, intricate, and variable. They must be highly sensitive, and pre-analytical, patient, and tumor-related factors significantly influence the detection threshold, diagnostic method selection, and potential results. Consequently, the implementation of LB in clinical practice still faces several challenges. The potential applications of LB range from early cancer detection to guiding targeted therapy or immunotherapy in both early and advanced cancer cases, monitoring treatment response, early identification of relapses, or assessing patient risk. On the other hand, gastric cancer (GC) is a disease often diagnosed at advanced stages. Despite recent advances in molecular understanding, the currently available treatment options have not substantially improved the prognosis for many of these patients. The application of LB in GC could be highly valuable as a non-invasive method for early diagnosis and for enhancing the management and outcomes of these patients. In this comprehensive review, from a pathologist's perspective, we provide an overview of the main options available in LB, delve into the fundamental principles of the most studied techniques, explore the potential utility of LB application in the context of GC, and address the obstacles that need to be overcome in the future to make this innovative technique a game-changer in cancer diagnosis and treatment within clinical practice.
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Affiliation(s)
- Cristina Díaz del Arco
- Department of Surgical Pathology, Health Research Institute of the Hospital Clínico San Carlos, Hospital Clínico San Carlos, Madrid 28040, Spain
- Department of Legal Medicine, Psychiatry and Pathology, Universidad Complutense de Madrid, Madrid 28040, Spain
| | - M Jesús Fernández Aceñero
- Department of Surgical Pathology, Health Research Institute of the Hospital Clínico San Carlos, Hospital Clínico San Carlos, Madrid 28040, Spain
- Department of Legal Medicine, Psychiatry and Pathology, Universidad Complutense de Madrid, Madrid 28040, Spain
| | - Luis Ortega Medina
- Department of Surgical Pathology, Health Research Institute of the Hospital Clínico San Carlos, Hospital Clínico San Carlos, Madrid 28040, Spain
- Department of Legal Medicine, Psychiatry and Pathology, Universidad Complutense de Madrid, Madrid 28040, Spain
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12
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Dastafkan Z, Rezvani N, Amini S. Diagnostic value of FOXF1 gene promoter-methylated DNA in the plasma samples of patients with colorectal cancer. Int J Biol Markers 2023; 38:194-202. [PMID: 37847578 DOI: 10.1177/03936155231207109] [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: 10/19/2023]
Abstract
BACKGROUND Epigenetic modifications such as DNA methylation in the CpG islands of genes occur at a high rate. In this study, we measured the methylation level of the promoter region of the FOXF1 gene as a new blood biomarker for the detection of colorectal cancer in the early stages. METHODS The methylation level of the promoter region of the FOXF1 gene was measured in the plasma samples of 50 colorectal cancer patients and 50 normal individuals. DNA was extracted after exposure to sodium bisulfite by the MethyLight polymerase chain reaction (PCR) method. The percentage of promoter region was measured in all samples, and statistical analysis was done using SPSS v24 software. RESULTS The average promoter region between the plasma samples of colorectal cancer patients and healthy individuals had a significant difference (P < 0.001). The average promoter region of the FOXF1 gene in tumor plasma samples was 7.1 and in the control samples was 0.48. The sensitivity and specificity of the sample plasma levels were 78% and 89.5%, respectively. CONCLUSION The promoter region value of the FOXF1 gene in plasma samples using the MethyLight PCR method had high sensitivity and specificity as a non-invasive method for colorectal cancer diagnosis. This research is the first report that has been presented regarding the investigation of FOXF1 gene methylation in plasma samples in colorectal cancer. Therefore, it is necessary to conduct more studies with larger size samples to evaluate the efficiency of the gene under investigation.
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Affiliation(s)
- Zahra Dastafkan
- Medical Genetics Laboratory, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Nayebali Rezvani
- Department of Clinical Biochemistry, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Sabrieh Amini
- Department of Biology, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran
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13
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Islam MS, Gopalan V, Lam AK, Shiddiky MJA. Current advances in detecting genetic and epigenetic biomarkers of colorectal cancer. Biosens Bioelectron 2023; 239:115611. [PMID: 37619478 DOI: 10.1016/j.bios.2023.115611] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 08/07/2023] [Accepted: 08/16/2023] [Indexed: 08/26/2023]
Abstract
Colorectal carcinoma (CRC) is the third most common cancer in terms of diagnosis and the second in terms of mortality. Recent studies have shown that various proteins, extracellular vesicles (i.e., exosomes), specific genetic variants, gene transcripts, cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and altered epigenetic patterns, can be used to detect, and assess the prognosis of CRC. Over the last decade, a plethora of conventional methodologies (e.g., polymerase chain reaction [PCR], direct sequencing, enzyme-linked immunosorbent assay [ELISA], microarray, in situ hybridization) as well as advanced analytical methodologies (e.g., microfluidics, electrochemical biosensors, surface-enhanced Raman spectroscopy [SERS]) have been developed for analyzing genetic and epigenetic biomarkers using both optical and non-optical tools. Despite these methodologies, no gold standard detection method has yet been implemented that can analyze CRC with high specificity and sensitivity in an inexpensive, simple, and time-efficient manner. Moreover, until now, no study has critically reviewed the advantages and limitations of these methodologies. Here, an overview of the most used genetic and epigenetic biomarkers for CRC and their detection methods are discussed. Furthermore, a summary of the major biological, technical, and clinical challenges and advantages/limitations of existing techniques is also presented.
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Affiliation(s)
- Md Sajedul Islam
- Cancer Molecular Pathology, School of Medicine & Dentistry, Griffith University, Gold Coast Campus, Southport, QLD, 4222, Australia; Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, 4222, Australia
| | - Vinod Gopalan
- Cancer Molecular Pathology, School of Medicine & Dentistry, Griffith University, Gold Coast Campus, Southport, QLD, 4222, Australia; Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, 4222, Australia.
| | - Alfred K Lam
- Cancer Molecular Pathology, School of Medicine & Dentistry, Griffith University, Gold Coast Campus, Southport, QLD, 4222, Australia; Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, 4222, Australia; Pathology Queensland, Gold Coast University Hospital, Southport, QLD, 4215, Australia
| | - Muhammad J A Shiddiky
- Rural Health Research Institute, Charles Sturt University, Orange, NSW, 2800, Australia.
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14
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Koinis F, Zafeiriou Z, Messaritakis I, Katsaounis P, Koumarianou A, Kontopodis E, Chantzara E, Aidarinis C, Lazarou A, Christodoulopoulos G, Emmanouilides C, Hatzidaki D, Kallergi G, Georgoulias V, Kotsakis A. Prognostic Role of Circulating Tumor Cells in Patients with Metastatic Castration-Resistant Prostate Cancer Receiving Cabazitaxel: A Prospective Biomarker Study. Cancers (Basel) 2023; 15:4511. [PMID: 37760481 PMCID: PMC10527446 DOI: 10.3390/cancers15184511] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2023] [Revised: 08/18/2023] [Accepted: 08/29/2023] [Indexed: 09/29/2023] Open
Abstract
RATIONAL Circulating tumor cells (CTCs) appear to be a promising tool for predicting the clinical outcome and monitoring the response to treatment in patients with solid tumors. The current study assessed the clinical relevance of monitoring CTCs in patients with metastatic castration resistant prostate cancer (mCRPC) treated with cabazitaxel. PATIENTS AND METHODS Patients with histologically confirmed mCRPC who were previously treated with a docetaxel-containing regimen and experienced disease progression were enrolled in this multicenter prospective study. CTC counts were enumerated using the CellSearch system at baseline (before cabazitaxel initiation), after one cabazitaxel cycle (post 1st cycle) and at disease progression (PD). Patients were stratified into predetermined CTC-positive and CTC-negative groups. The phenotypic characterization was performed using double immunofluorescence staining with anti-CKs and anti-Ki67, anti-M30 or anti-vimentin antibodies. RESULTS The median PFS and OS were 4.0 (range, 1.0-17.9) and 14.5 (range, 1.2-33.9) months, respectively. At baseline, 48 out of 57 (84.2%) patients had ≥1 CTCs/7.5 mL of peripheral blood (PB) and 37 (64.9%) had ≥5 CTCs/7.5 mL of PB. After one treatment cycle, 30 (75%) out of the 40 patients with available measurements had ≥1 detectable CTC/7.5 mL of PB and 24 (60%) ≥ 5CTCs/7.5 mL of PB; 12.5% of the patients with detectable CTCs at the baseline sample had no detectable CTCs after one treatment cycle. The detection of ≥5CTCs/7.5 mL of PB at baseline and post-cycle 1 was associated with shorter PFS and OS (p = 0.002), whereas a positive CTC status post-cycle 1 strongly correlated with poorer OS irrespective of the CTC cut-off used. Multivariate analysis revealed that the detection of non-apoptotic (CK+/M30-) CTCs at baseline is an independent predictor of shorter OS (p = 0.005). CONCLUSIONS In patients with mCRPC treated with cabazitaxel, CTC counts both at baseline and after the first cycle retain their prognostic significance, implying that liquid biopsy monitoring might serve as a valuable tool for predicting treatment efficacy and survival outcomes.
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Affiliation(s)
- Filippos Koinis
- Department of Medical Oncology, University General Hospital of Larissa, 41334 Larisa, Greece; (E.C.); (C.A.); (A.L.); (G.C.)
- Faculty οf Medicine, School of Health Sciences, University of Thessaly, 41335 Larissa, Greece
| | - Zafeiris Zafeiriou
- Second Department of Medical Oncology, Theageneion Anticancer Hospital, 54007 Thessaloniki, Greece;
| | - Ippokratis Messaritakis
- Laboratory of Tumor Cell Biology, School of Medicine, University of Crete, Heraklion, 70013 Crete, Greece;
| | - Panagiotis Katsaounis
- First Department of Medical Oncology, Metropolitan General Hospital, 15562 Athens, Greece; (P.K.); (V.G.)
| | - Anna Koumarianou
- Medical Oncology Unit, 4th Department of Internal Medicine, “ATTIKON” University Hospital of Athens, 11528 Athens, Greece;
| | - Emmanouil Kontopodis
- Department of Medical Oncology, “Venizelion” General Hospital of Heraklion, 71409 Crete, Greece;
| | - Evangelia Chantzara
- Department of Medical Oncology, University General Hospital of Larissa, 41334 Larisa, Greece; (E.C.); (C.A.); (A.L.); (G.C.)
| | - Chrissovalantis Aidarinis
- Department of Medical Oncology, University General Hospital of Larissa, 41334 Larisa, Greece; (E.C.); (C.A.); (A.L.); (G.C.)
| | - Alexandros Lazarou
- Department of Medical Oncology, University General Hospital of Larissa, 41334 Larisa, Greece; (E.C.); (C.A.); (A.L.); (G.C.)
| | - George Christodoulopoulos
- Department of Medical Oncology, University General Hospital of Larissa, 41334 Larisa, Greece; (E.C.); (C.A.); (A.L.); (G.C.)
| | - Christos Emmanouilides
- Department of Medical Oncology, Diavalkanikon General Hospital of Thessaloniki, 55535 Thessaloniki, Greece;
| | - Dora Hatzidaki
- Hellenic Oncology Research Group (HORG), 11526 Athens, Greece;
| | - Galatea Kallergi
- Division of Genetics, Cell and Developmental Biology, Department of Biology, University of Patras, 26504 Patras, Greece;
| | - Vassilis Georgoulias
- First Department of Medical Oncology, Metropolitan General Hospital, 15562 Athens, Greece; (P.K.); (V.G.)
- Hellenic Oncology Research Group (HORG), 11526 Athens, Greece;
| | - Athanasios Kotsakis
- Department of Medical Oncology, University General Hospital of Larissa, 41334 Larisa, Greece; (E.C.); (C.A.); (A.L.); (G.C.)
- Faculty οf Medicine, School of Health Sciences, University of Thessaly, 41335 Larissa, Greece
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15
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Wang W, Zheng Z, Lei J. CTC, ctDNA, and Exosome in Thyroid Cancers: A Review. Int J Mol Sci 2023; 24:13767. [PMID: 37762070 PMCID: PMC10530859 DOI: 10.3390/ijms241813767] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/11/2023] [Revised: 08/29/2023] [Accepted: 09/04/2023] [Indexed: 09/29/2023] Open
Abstract
Thyroid cancer has become more common in recent years all around the world. Many issues still need to be urgently addressed in the diagnosis, treatment, and prognosis of thyroid cancer. Liquid biopsy (mainly circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and circulating exosomes) may provide a novel and ideal approach to solve these issues, allows us to assess the features of diseases more comprehensively, and has a function in a variety of malignancies. Recently, liquid biopsy has been shown to be critical in thyroid cancer diagnosis, treatment, and prognosis in numerous previous studies. In this review, by testing CTCs, ctDNA, and exosomes, we focus on the possible clinical role of liquid biopsy in thyroid cancer, including diagnostic and prognostic biomarkers and response to therapy. We briefly review how liquid biopsy components have progressed in thyroid cancer by consulting the existing public information. We also discuss the clinical potential of liquid biopsy in thyroid cancer and provide a reference for liquid biopsy research. Liquid biopsy has the potential to be a useful tool in the early detection, monitoring, or prediction of response to therapies and prognosis in thyroid cancer, with promising clinical applications.
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Affiliation(s)
- Wenwen Wang
- Division of Thyroid Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Zhiyao Zheng
- Division of Thyroid Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
- Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
| | - Jianyong Lei
- Division of Thyroid Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, China
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Serrano MJ, Rolfo C, Expósito-Hernandez J, Garrido-Navas C, Lopez-Hidalgo J, Denninghoff V. Circulating tumor cells in cancer-risk populations as a cancer interception tool. INTERNATIONAL REVIEW OF CELL AND MOLECULAR BIOLOGY 2023; 381:113-129. [PMID: 37739481 DOI: 10.1016/bs.ircmb.2023.07.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/24/2023]
Abstract
Cancer interception (CI) is a new approach to cancer prevention and treatment in a cancer-risk population that aims to detect and treat pre-tumoral stages. It has several potential advantages over traditional cancer diagnosis and monitoring methods because it is non-invasive, making it less painful and risky than conventional biopsy procedures. The circulating tumor cells (CTCs), liquid biopsy family members, are essential for the CI approach; then, the liquid biopsy (LB) is used as a CI tool. LB can be performed frequently because of its easy sampling and early pathological stages, which allow repeated non-invasive monitoring of cancer progression and response to treatment. CTCs have been found in the bloodstream of several types of cancer patients, including in early-stage cancer and premalignant lesions, suggesting a tumor development role in cancer's early stages. This chapter will present foundational scientific studies addressing CI and the clinical impact of CTC screening in a population at risk for cancer.
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Affiliation(s)
- María José Serrano
- GENYO Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, Liquid Biopsy and Cancer Interception Group, Granada, Spain; IBS Granada, Biosanitary Research Institute, Spain; Comprehensive Oncology Division, Virgen de las Nieves University Hospital, Granada, Spain.
| | - Christian Rolfo
- Center for Thoracic Oncology, The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York City, NY, United States
| | - José Expósito-Hernandez
- GENYO Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, Liquid Biopsy and Cancer Interception Group, Granada, Spain; IBS Granada, Biosanitary Research Institute, Spain; Comprehensive Oncology Division, Virgen de las Nieves University Hospital, Granada, Spain
| | - Carmen Garrido-Navas
- IBS Granada, Biosanitary Research Institute, Spain; Comprehensive Oncology Division, Virgen de las Nieves University Hospital, Granada, Spain
| | - Javier Lopez-Hidalgo
- Department of Pathological Anatomy, Faculty of Medicine, University of Granada, Spain
| | - Valeria Denninghoff
- GENYO Centre for Genomics and Oncological Research: Pfizer, University of Granada, Andalusian Regional Government, Liquid Biopsy and Cancer Interception Group, Granada, Spain; Molecular-Clinical Lab - University of Buenos Aires (UBA) - National Council for Scientific and Technical Research (CONICET), Argentina.
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17
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Mishra PK, Kaur P. Future-ready technologies for sensing the stemness of circulating tumor cells. Nanomedicine (Lond) 2023; 18:1327-1330. [PMID: 37585672 DOI: 10.2217/nnm-2023-0066] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/18/2023] Open
Affiliation(s)
- Pradyumna Kumar Mishra
- Division of Environmental Biotechnology, Genetics and Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, 462030, India
| | - Prasan Kaur
- Division of Environmental Biotechnology, Genetics and Molecular Biology, ICMR-National Institute for Research in Environmental Health, Bhopal, 462030, India
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18
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Rapanotti MC, Cugini E, Campione E, Di Raimondo C, Costanza G, Rossi P, Ferlosio A, Bernardini S, Orlandi A, De Luca A, Bianchi L. Epithelial-to-Mesenchymal Transition Gene Signature in Circulating Melanoma Cells: Biological and Clinical Relevance. Int J Mol Sci 2023; 24:11792. [PMID: 37511550 PMCID: PMC10380315 DOI: 10.3390/ijms241411792] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Revised: 07/14/2023] [Accepted: 07/20/2023] [Indexed: 07/30/2023] Open
Abstract
The most promising method for monitoring patients with minimal morbidity is the detection of circulating melanoma cells (CMCs). We have shown that CD45-CD146+ABCB5+ CMCs identify a rare primitive stem/mesenchymal CMCs population associated with disease progression. The epithelial-to-mesenchymal transition (EMT) confers cancer cells a hybrid epithelial/mesenchymal phenotype promoting metastatization. Thus, we investigated the potential clinical value of the EMT gene signature of these primitive CMCs. A reliable quantitative real-time polymerase chain reaction (qRT-PCR) protocol was settled up using tumor cell lines RNA dilutions. Afterwards, immune-magnetically isolated CMCs from advanced melanoma patients, at onset and at the first checkpoint (following immune or targeted therapy), were tested for the level of EMT hallmarks and EMT transcription factor genes. Despite the small cohort of patients, we obtained promising results. Indeed, we observed a deep gene rewiring of the EMT investigated genes: in particular we found that the EMT gene signature of isolated CMCs correlated with patients' clinical outcomes. In conclusion, We established a reliable qRT-PCR protocol with high sensitivity and specificity to characterize the gene expression of isolated CMCs. To our knowledge, this is the first evidence demonstrating the impact of immune or targeted therapies on EMT hallmark gene expressions in CMCs from advanced melanoma patients.
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Affiliation(s)
- Maria Cristina Rapanotti
- Department of Anatomic Pathology, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
- Department of Laboratory Medicine, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
| | - Elisa Cugini
- Department of Laboratory Medicine, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
| | - Elena Campione
- Dermatology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
| | - Cosimo Di Raimondo
- Dermatology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
| | - Gaetana Costanza
- Department of Laboratory Medicine, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
| | - Piero Rossi
- Surgery Division, Department of Surgery Sciences, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
| | - Amedeo Ferlosio
- Department of Anatomic Pathology, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
| | - Sergio Bernardini
- Department of Laboratory Medicine, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
| | - Augusto Orlandi
- Department of Anatomic Pathology, University of Rome Tor Vergata, Viale Oxford 81, 00133 Rome, Italy
| | - Anastasia De Luca
- Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica 1, 00133 Rome, Italy
| | - Luca Bianchi
- Dermatology Unit, Department of Systems Medicine, University of Rome Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
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Mirza S, Bhadresha K, Mughal MJ, McCabe M, Shahbazi R, Ruff P, Penny C. Liquid biopsy approaches and immunotherapy in colorectal cancer for precision medicine: Are we there yet? Front Oncol 2023; 12:1023565. [PMID: 36686736 PMCID: PMC9853908 DOI: 10.3389/fonc.2022.1023565] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Accepted: 12/08/2022] [Indexed: 01/07/2023] Open
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer-related deaths globally, with nearly half of patients detected in the advanced stages. This is due to the fact that symptoms associated with CRC often do not appear until the cancer has reached an advanced stage. This suggests that CRC is a cancer with a slow progression, making it curable and preventive if detected in its early stage. Therefore, there is an urgent clinical need to improve CRC early detection and personalize therapy for patients with this cancer. Recently, liquid biopsy as a non-invasive or nominally invasive approach has attracted considerable interest for its real-time disease monitoring capability through repeated sample analysis. Several studies in CRC have revealed the potential for liquid biopsy application in a real clinical setting using circulating RNA/miRNA, circulating tumor cells (CTCs), exosomes, etc. However, Liquid biopsy still remains a challenge since there are currently no promising results with high specificity and specificity that might be employed as optimal circulatory biomarkers. Therefore, in this review, we conferred the plausible role of less explored liquid biopsy components like mitochondrial DNA (mtDNA), organoid model of CTCs, and circulating cancer-associated fibroblasts (cCAFs); which may allow researchers to develop improved strategies to unravel unfulfilled clinical requirements in CRC patients. Moreover, we have also discussed immunotherapy approaches to improve the prognosis of MSI (Microsatellite Instability) CRC patients using neoantigens and immune cells in the tumor microenvironment (TME) as a liquid biopsy approach in detail.
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Affiliation(s)
- Sheefa Mirza
- Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa,Department of Internal Medicine, Common Epithelial Cancer Research Centre, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Kinjal Bhadresha
- Hematology/Oncology Division, School of Medicine, Indiana University, Indianapolis, IN, United States
| | - Muhammed Jameel Mughal
- Department of Biochemistry and Molecular Medicine, School of Medicine and Health Science, The George Washington University, Washington, DC, United States
| | - Michelle McCabe
- Department of Anatomical Pathology, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Parktown, Johannesburg, South Africa
| | - Reza Shahbazi
- Hematology/Oncology Division, School of Medicine, Indiana University, Indianapolis, IN, United States
| | - Paul Ruff
- Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa,Department of Internal Medicine, Common Epithelial Cancer Research Centre, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa
| | - Clement Penny
- Department of Internal Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa,Department of Internal Medicine, Common Epithelial Cancer Research Centre, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa,*Correspondence: Clement Penny,
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20
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Couto-Cunha A, Jerónimo C, Henrique R. Circulating Tumor Cells as Biomarkers for Renal Cell Carcinoma: Ready for Prime Time? Cancers (Basel) 2022; 15:cancers15010287. [PMID: 36612281 PMCID: PMC9818240 DOI: 10.3390/cancers15010287] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2022] [Revised: 12/19/2022] [Accepted: 12/28/2022] [Indexed: 01/03/2023] Open
Abstract
Renal cell carcinoma (RCC) is among the 15 most common cancers worldwide, with rising incidence. In most cases, this is a silent disease until it reaches advance stages, demanding new effective biomarkers in all domains, from detection to post-therapy monitoring. Circulating tumor cells (CTC) have the potential to provide minimally invasive information to guide assessment of the disease's aggressiveness and therapeutic strategy, representing a special pool of neoplastic cells which bear metastatic potential. In some tumor models, CTCs' enumeration has been associated with prognosis, but there is a largely unexplored potential for clinical applicability encompassing screening, diagnosis, early detection of metastases, prognosis, response to therapy and monitoring. Nonetheless, lack of standardization and high cost hinder the translation into clinical practice. Thus, new methods for collection and analysis (genomic, proteomic, transcriptomic, epigenomic and metabolomic) are needed to ascertain the role of CTC as a RCC biomarker. Herein, we provide a critical overview of the most recently published data on the role and clinical potential of CTCs in RCC, addressing their biology and the molecular characterization of this remarkable set of tumor cells. Furthermore, we highlight the existing and emerging techniques for CTC enrichment and detection, exploring clinical applications in RCC. Notwithstanding the notable progress in recent years, the use of CTCs in a routine clinical scenario of RCC patients requires further research and technological development, enabling multimodal analysis to take advantage of the wealth of information they provide.
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Affiliation(s)
- Anabela Couto-Cunha
- Integrated Master in Medicine, School of Medicine & Biomedical Sciences, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
| | - Carmen Jerónimo
- Department of Pathology and Molecular Immunology, School of Medicine & Biomedical Sciences, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
- Department of Pathology & Cancer Biology & Epigenetics Group—Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Centre Raquel Seruca (P.CCC Raquel Seruca), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
| | - Rui Henrique
- Department of Pathology and Molecular Immunology, School of Medicine & Biomedical Sciences, University of Porto (ICBAS-UP), Rua Jorge Viterbo Ferreira 228, 4050-313 Porto, Portugal
- Department of Pathology & Cancer Biology & Epigenetics Group—Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO-Porto)/Porto Comprehensive Cancer Centre Raquel Seruca (P.CCC Raquel Seruca), Rua Dr. António Bernardino de Almeida, 4200-072 Porto, Portugal
- Correspondence: or
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21
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Galoș D, Gorzo A, Balacescu O, Sur D. Clinical Applications of Liquid Biopsy in Colorectal Cancer Screening: Current Challenges and Future Perspectives. Cells 2022; 11:3493. [PMID: 36359889 PMCID: PMC9657568 DOI: 10.3390/cells11213493] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2022] [Revised: 10/26/2022] [Accepted: 11/02/2022] [Indexed: 08/13/2023] Open
Abstract
Colorectal cancer (CRC) represents the third most prevalent cancer worldwide and a leading cause of mortality among the population of western countries. However, CRC is frequently a preventable malignancy due to various screening tests being available. While failing to obtain real-time data, current screening methods (either endoscopic or stool-based tests) also require disagreeable preparation protocols and tissue sampling through invasive procedures, rendering adherence to CRC screening programs suboptimal. In this context, the necessity for novel, less invasive biomarkers able to identify and assess cancer at an early stage is evident. Liquid biopsy comes as a promising minimally invasive diagnostic tool, able to provide comprehensive information on tumor heterogeneity and dynamics during carcinogenesis. This review focuses on the potential use of circulating tumor cells (CTCs), circulating nucleic acids (CNAs) and extracellular vesicles as emerging liquid biopsy markers with clinical application in the setting of CRC screening. The review also examines the opportunity to implement liquid biopsy analysis during everyday practice and provides highlights on clinical trials researching blood tests designed for early cancer diagnosis. Additionally, the review explores potential applications of liquid biopsies in the era of immunotherapy.
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Affiliation(s)
- Diana Galoș
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuţă”, 400015 Cluj-Napoca, Romania
| | - Alecsandra Gorzo
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuţă”, 400015 Cluj-Napoca, Romania
| | - Ovidiu Balacescu
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuţă”, 400015 Cluj-Napoca, Romania
- Department of Genetics, Genomics and Experimental Pathology, The Oncology Institute “Prof. Dr. Ion Chiricuţă”, 400015 Cluj-Napoca, Romania
| | - Daniel Sur
- Department of Medical Oncology, The Oncology Institute “Prof. Dr. Ion Chiricuţă”, 400015 Cluj-Napoca, Romania
- Department of Medical Oncology, University of Medicine and Pharmacy “Iuliu Hațieganu”, 400012 Cluj-Napoca, Romania
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22
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Wu J, Li Z, Zou J, Li L, Cui N, Hao T, Yi K, Yang J, Wu Y. A meta-analysis of the value of circulating tumor cells in monitoring postoperative recurrence and metastasis of colorectal cancer. PLoS One 2022; 17:e0274282. [PMID: 36121855 PMCID: PMC9484659 DOI: 10.1371/journal.pone.0274282] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2021] [Accepted: 08/24/2022] [Indexed: 11/19/2022] Open
Abstract
Objective Circulating tumor cells (CTCs) as novel biomarkers are widely investigated in various cancers, although most of the literature shows that CTCs have predictive value for recurrence, metastasis, and prognosis after CRC surgery, results remain controversial. We aimed to systematically evaluate the value of CTCs in monitoring of colorectal cancer (CRC) recurrence and metastasis after surgery. Method The PubMed, Cochrane Library, Embase, and other databases were searched from the establishment of the database to May 27, 2021. Relevant literature searches and data extraction were performed independently by two reviewers. The quality assessment was performed using the QUADAS2 scale developed by the Cochrane collaboration. The heterogeneity was checked using the Spearman correlation coefficient and the Cochran-Q test in the Meta-Disc1.4 software. Subgroup analysis was used to explore the source of heterogeneity. Considering that all the included papers were clinical studies with clinical heterogeneity, random effect model was adopted for analysis. And the sensitivity (Sen), specificity (Spe), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic (SROC) curves of CTCs, in monitoring recurrence and metastasis after CRC, were calculated. The publication bias of the included studies was assessed using Deek’s funnel figure. Result The literature included a total of 13 articles, comprising 1788 cases, and the overall quality of the literature was high. After summing up the indicators, the sensitivity pooled-value of the peripheral blood CTCs to monitor the recurrence and metastasis value of CRC after CRC was 0.67 [95%CI (0.62, 0.71)], specificity pooled-value was 0.71 [95%CI (0.67, 0.72)], PLR pooled-value was 2.37 [95%CI [1.52, 3.71]), NLR pooled into 0.53 [95%CI (0.36, 0.78)], DOR pooled into 4.97 [95%CI (2.11, 11.72)], AUC was 0.7395. Conclusion Peripheral blood CTCs have a moderate monitoring value for recurrence and metastasis after CRC; CTCs detected one week after surgery may be more correlated with recurrence and metastasis.
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Affiliation(s)
- Jiao Wu
- Oncology Department of Xiyuan Hospital, China Academy of Chinese Medical Science Haidian District, Beijing, China
| | - Zhongyu Li
- Oncology Department of Xiyuan Hospital, China Academy of Chinese Medical Science Haidian District, Beijing, China
| | - Jianhua Zou
- Oncology Department of Xiyuan Hospital, China Academy of Chinese Medical Science Haidian District, Beijing, China
| | - Liusheng Li
- Oncology Department of Xiyuan Hospital, China Academy of Chinese Medical Science Haidian District, Beijing, China
| | - Ning Cui
- Oncology Department of Xiyuan Hospital, China Academy of Chinese Medical Science Haidian District, Beijing, China
| | - Tengteng Hao
- Oncology Department of Xiyuan Hospital, China Academy of Chinese Medical Science Haidian District, Beijing, China
| | - Kangjun Yi
- Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Jingyan Yang
- Graduate School of Beijing University of Chinese Medicine, Beijing, China
| | - Yu Wu
- Oncology Department of Xiyuan Hospital, China Academy of Chinese Medical Science Haidian District, Beijing, China
- Graduate School of Beijing University of Chinese Medicine, Beijing, China
- * E-mail:
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23
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Advances in the Biology, Detection Techniques, and Clinical Applications of Circulating Tumor Cells. JOURNAL OF ONCOLOGY 2022; 2022:7149686. [PMID: 36090904 PMCID: PMC9462976 DOI: 10.1155/2022/7149686] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 07/12/2022] [Accepted: 08/02/2022] [Indexed: 12/01/2022]
Abstract
Circulating tumor cells (CTCs) play a crucial role in tumor recurrence and metastasis, and their early detection has shown remarkable benefits in clinical theranostics. However, CTCs are extremely rare, thus detecting them in the blood is very challenging. New CTC detection techniques are continuously being developed, enabling deeper analysis of CTC biology and potential clinical application. This article reviews current CTC detection techniques and their clinical application. CTCs have provided, and will continue to provide, important insights into the process of metastasis, which could lead to development of new therapies for different cancers.
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24
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Functional Precision Oncology: The Next Frontier to Improve Glioblastoma Outcome? Int J Mol Sci 2022; 23:ijms23158637. [PMID: 35955765 PMCID: PMC9369403 DOI: 10.3390/ijms23158637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2022] [Revised: 07/31/2022] [Accepted: 08/01/2022] [Indexed: 11/30/2022] Open
Abstract
Glioblastoma remains the most malignant and intrinsically resistant brain tumour in adults. Despite intensive research over the past few decades, through which numerous potentially druggable targets have been identified, virtually all clinical trials of the past 20 years have failed to improve the outcome for the vast majority of GBM patients. The observation that small subgroups of patients displayed a therapeutic response across several unsuccessful clinical trials suggests that the GBM patient population probably consists of multiple subgroups that probably all require a distinct therapeutic approach. Due to extensive inter- and intratumoral heterogeneity, assigning the right therapy to each patient remains a major challenge. Classically, bulk genetic profiling would be used to identify suitable therapies, although the success of this approach remains limited due to tumor heterogeneity and the absence of direct relationships between mutations and therapy responses in GBM. An attractive novel strategy aims at implementing methods for functional precision oncology, which refers to the evaluation of treatment efficacies and vulnerabilities of (ex vivo) living tumor cells in a highly personalized way. Such approaches are currently being implemented for other cancer types by providing rapid, translatable information to guide patient-tailored therapeutic selections. In this review, we discuss the current state of the art of transforming technologies, tools and challenges for functional precision oncology and how these could improve therapy selection for GBM patients.
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25
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Rehman AU, Khan P, Maurya SK, Siddiqui JA, Santamaria-Barria JA, Batra SK, Nasser MW. Liquid biopsies to occult brain metastasis. Mol Cancer 2022; 21:113. [PMID: 35538484 PMCID: PMC9088117 DOI: 10.1186/s12943-022-01577-x] [Citation(s) in RCA: 39] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2021] [Accepted: 04/19/2022] [Indexed: 02/08/2023] Open
Abstract
Brain metastasis (BrM) is a major problem associated with cancer-related mortality, and currently, no specific biomarkers are available in clinical settings for early detection. Liquid biopsy is widely accepted as a non-invasive method for diagnosing cancer and other diseases. We have reviewed the evidence that shows how the molecular alterations are involved in BrM, majorly from breast cancer (BC), lung cancer (LC), and melanoma, with an inception in how they can be employed for biomarker development. We discussed genetic and epigenetic changes that influence cancer cells to breach the blood-brain barrier (BBB) and help to establish metastatic lesions in the uniquely distinct brain microenvironment. Keeping abreast with the recent breakthroughs in the context of various biomolecules detections and identifications, the circulating tumor cells (CTC), cell-free nucleotides, non-coding RNAs, secretory proteins, and metabolites can be pursued in human body fluids such as blood, serum, cerebrospinal fluid (CSF), and urine to obtain potential candidates for biomarker development. The liquid biopsy-based biomarkers can overlay with current imaging techniques to amplify the signal viable for improving the early detection and treatments of occult BrM.
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Affiliation(s)
- Asad Ur Rehman
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68108, USA
| | - Parvez Khan
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68108, USA
| | - Shailendra Kumar Maurya
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68108, USA
| | - Jawed A Siddiqui
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68108, USA.,Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68108, USA
| | | | - Surinder K Batra
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68108, USA.,Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68108, USA.,Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE-68198, USA
| | - Mohd Wasim Nasser
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68108, USA. .,Fred and Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68108, USA.
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26
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Li H, Huang B. <em>miR-19a</em> targeting <em>CLCA4</em> to regulate the proliferation, migration, and invasion of colorectal cancer cells. Eur J Histochem 2022; 66. [PMID: 35266369 PMCID: PMC8958453 DOI: 10.4081/ejh.2022.3381] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2022] [Accepted: 02/19/2022] [Indexed: 12/24/2022] Open
Abstract
The role of miR-19a in colorectal cancer (CRC), a devastating disease with high mortality and morbidity, remains controversial. In the present study, we show that the level of miR-19a is significantly higher in clinical CRC tissue samples than in paracancerous tissue samples, and significantly higher in CRC cells lines HT29, SW480, and CaCO2 than in the normal human colon mucosal epithelial cell line NCM460. miR-19a mimics and inhibitors were synthesized and validated. Overexpression of miR-19a mimics significantly promoted, while miR-19a inhibitors inhibited, the proliferation, survival, migration, and invasion of SW480 and CaCO2 CRC cells. Furthermore, mRNA and protein levels of chloride channel accessory 4 (CLCA4) were lower in CRC cells and tissues. Bioinformatics and a luciferase reporter assay confirmed that CLCA4 was a miR-19a target. Further, miR-19a inhibition increased CLCA4 expression. The inhibitory effect of miR-19a on cell growth, survival, migration, and invasion was reversed by knockdown of CLCA4 expression. The data demonstrated that the miR-19a/CLCA4 axis modulates phospho-activation of the PI3K/AKT pathway in CRC cells. In conclusion, our results revealed that miR-19a overexpression decreases CLCA4 levels to promote CRC oncogenesis, suggesting that miR-19a inhibitors have potential applications for future therapeutic of CRC.
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Affiliation(s)
- Huiwen Li
- Department of Pediatrics, the First Affiliated Hospital of Jinan University, Guangzhou; Department of Gastroenterology, Guangzhou Women and Children's Medical Center, Guangzhou.
| | - Bo Huang
- Department of Gastrointestinal Surgery, Guangzhou Red Cross Hospital, Jinan University, Guangzhou.
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