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Budhbaware T, Rathored J, Shende S. Molecular methods in cancer diagnostics: a short review. Ann Med 2024; 56:2353893. [PMID: 38753424 PMCID: PMC11100444 DOI: 10.1080/07853890.2024.2353893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 04/18/2024] [Indexed: 05/18/2024] Open
Abstract
BACKGROUND One of the ailments with the greatest fatality rates in the 21st century is cancer. Globally, molecular methods are widely employed to treat cancer-related disorders, and the body of research on this subject is growing yearly. A thorough and critical summary of the data supporting molecular methods for illnesses linked to cancer is required. OBJECTIVE In order to guide clinical practice and future research, it is important to examine and summarize the systematic reviews (SRs) that evaluate the efficacy and safety of molecular methods for disorders associated to cancer. METHODS We developed a comprehensive search strategy to find relevant articles from electronic databases like PubMed, Google Scholar, Web of Science (WoS), or Scopus. We looked through the literature and determined which diagnostic methods in cancer genetics were particularly reliable. We used phrases like 'cancer genetics', genetic susceptibility, Hereditary cancer, cancer risk assessment, 'cancer diagnostic tools', cancer screening', biomarkers, and molecular diagnostics, reviews and meta-analyses evaluating the efficacy and safety of molecular therapies for cancer-related disorders. Research that only consider treatment modalities that don't necessitate genetic or molecular diagnostics fall under the exclusion criteria. RESULTS The results of this comprehensive review clearly demonstrate the transformative impact of molecular methods in the realm of cancer genetics.This review underscores how these technologies have empowered researchers and clinicians to identify and understand key genetic alterations that drive malignancy, ranging from point mutations to structural variations. Such insights are instrumental in pinpointing critical oncogenic drivers and potential therapeutic targets, thus opening the door for methods in precision medicine that can significantly improve patient outcomes. LIMITATION The search does not specify a timeframe for publication inclusion, it may have missed recent advancements or changes in the field's landscape of molecular methods for cancer. As a result, it may not have included the most recent developments in the field. CONCLUSION After conducting an in-depth study on the molecular methods in cancer genetics, it is evident that these cutting-edge technologies have revolutionized the field of oncology, providing researchers and clinicians with powerful tools to unravel the complexities of cancer at the genetic level. The integration of molecular methods techniques has not only enhanced our understanding of cancer etiology, progression, and treatment response but has also opened new avenues for personalized medicine and targeted therapies, leading to improved patient outcomes.
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Affiliation(s)
- Tanushree Budhbaware
- Department of ‘School of Allied Health Sciences’, Central Research Laboratory (CRL) and Molecular Diagnostics, Datta Meghe Institute of Higher Education and Research, Sawangi (Meghe), Wardha, India
| | - Jaishriram Rathored
- Department of ‘School of Allied Health Sciences’, Central Research Laboratory (CRL) and Molecular Diagnostics, Datta Meghe Institute of Higher Education and Research, Sawangi (Meghe), Wardha, India
| | - Sandesh Shende
- Department of ‘School of Allied Health Sciences’, Central Research Laboratory (CRL) and Molecular Diagnostics, Datta Meghe Institute of Higher Education and Research, Sawangi (Meghe), Wardha, India
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Sun Y, Zhang C. The types of tumor infiltrating lymphocytes are valuable for the diagnosis and prognosis of breast cancer. Front Genet 2022; 13:1019062. [DOI: 10.3389/fgene.2022.1019062] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2022] [Accepted: 10/10/2022] [Indexed: 11/13/2022] Open
Abstract
This study aimed at constructing a diagnostic immune risk score (dIRS) system and a prognostic immune risk score (pIRS) system for diagnose and prognosis of breast cancer (BC). The gene expression data of BC were downloaded from TCGA dataset (training set), and from GSE65194, GSE29044, GSE42568, and GSE20685 (validation sets). Then, the immune cell type proportions in each dataset were assessed using EPIC tool, and the dIRS system was built based on the SVM-RFE and RF-VIMP algorithms. Subsequently, the pIRS system and the nomogram survival model were established separately using penalized and rms packages. Finally, the differential expressed genes (DEGs) between low and high pIRS groups were screened, and submitted for functional analysis. The dIRS system consisted of B cells, CD8 + T cells, endothelial cells, NK cells, and other cells had high accuracy in distinguishing BC patients from the healthy controls (AUROC >0.7). Subsequently, the pIRS system with the five prognosis-associated immune-infiltrating cell was constructed, and Kaplan-Meier analysis demonstrated that the survival rate of low pIRS group was significantly higher than that of high pIRS group (p < 0.05). Based on age, pathologic stage and the pIRS values, the nomogram survival model was built. The AUROC value, Specificity value, Sensitivity value and C-index of the nomogram survival model were higher than 0.7000, and had a good predictive ability for BC. Finally, a total of 539 DEGs were identified, and significantly enriched in six pathways. The dIRS system and the pIRS system composed of immune cells might be critical for the diagnosis and prognosis of BC patients.
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Construction and Validation of a Newly Prognostic Signature for CRISPR-Cas9-Based Cancer Dependency Map Genes in Breast Cancer. JOURNAL OF ONCOLOGY 2022; 2022:4566577. [PMID: 35096059 PMCID: PMC8791742 DOI: 10.1155/2022/4566577] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/24/2021] [Accepted: 12/01/2021] [Indexed: 12/11/2022]
Abstract
Cancer Dependency Map (CDM) genes comprise an extensive series of genome-scale RNAi-based loss-of-function tests; hence, it served as a method based on the CRISPR-Cas9 technique that could assist scientists in investigating potential gene functions. These CDM genes have a role in tumor cell survival and proliferation, suggesting that they may be used as new therapeutic targets for some malignant tumors. So far, there have been less research on the involvement of CDM genes in breast cancer, and only a tiny percentage of CDM genes have been studied. In this study, information of patients with breast cancer was extracted from The Cancer Genome Atlas (TCGA), from which differentially expressed CDM genes in breast cancer were determined. A variety of bioinformatics techniques were used to assess the functions and prognostic relevance of these confirmed CDM genes. In all, 290 CDM genes were found differentially expressed. Six CDM genes (SRF, RAD51, PMF1, EXOSC3, EXOC1, and TSEN54) were found to be associated with the prognosis of breast cancer samples. Based on the expression of the identified CDM genes and their coefficients, a prognosis model was constructed for prediction, according to which patients with breast cancer were separated into two risk groups. Those with high risk had substantially poorer overall survival (OS) than patients in the other risk group in the TCGA training set, TCGA testing set, and an external cohort from Gene Expression Omnibus (GEO) database. The area under the receiver operating characteristic (ROC) curve for this prognostic signature was, respectively, 0.717 and 0.635 for TCGA training and testing sets, demonstrating its reliability in predicting the prognosis of patients with breast cancer. We next created a nomogram using the six CDM genes discovered to create a therapeutically useful model. The Human Protein Atlas database was used to acquire all immunohistochemistry staining images of the discovered CDM genes. The proportions of tumor-infiltrating immune cells, as well as the expression levels of checkpoint genes, varied substantially between the two risk groups, according to the analyses of immune response. In conclusion, the findings of this research may aid in the understanding of the prognostic value and biological roles of CDM genes in breast cancer.
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Davidson BA, Croessmann S, Park BH. The breast is yet to come: current and future utility of circulating tumour DNA in breast cancer. Br J Cancer 2021; 125:780-788. [PMID: 34040179 PMCID: PMC8438047 DOI: 10.1038/s41416-021-01422-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2020] [Revised: 04/02/2021] [Accepted: 04/21/2021] [Indexed: 02/06/2023] Open
Abstract
Advances in genomic strategies and the development of targeted therapies have enabled precision medicine to revolutionise the field of oncology. Precision medicine uses patient-specific genetic and molecular information, traditionally obtained from tumour biopsy samples, to classify tumours and treat them accordingly. However, biopsy samples often fail to provide complete tumour profiling, and the technique is expensive and, of course, relatively invasive. Advances in genomic techniques have led to improvements in the isolation and detection of circulating tumour DNA (ctDNA), a component of a peripheral blood draw/liquid biopsy. Liquid biopsy offers a minimally invasive method to gather genetic information that is representative of a global snapshot of both primary and metastatic sites and can thereby provide invaluable information for potential targeted therapies and methods for tumour surveillance. However, a lack of prospective clinical trials showing direct patient benefit has limited the implementation of liquid biopsies in standard clinical applications. Here, we review the potential of ctDNA obtained by liquid biopsy to revolutionise personalised medicine and discuss current applications of ctDNA both at the benchtop and bedside.
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Affiliation(s)
- Brad A Davidson
- The Vanderbilt-Ingram Cancer Center, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Sarah Croessmann
- The Vanderbilt-Ingram Cancer Center, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Ben H Park
- The Vanderbilt-Ingram Cancer Center, Division of Hematology/Oncology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
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Cusenza VY, Bisagni A, Rinaldini M, Cattani C, Frazzi R. Copy Number Variation and Rearrangements Assessment in Cancer: Comparison of Droplet Digital PCR with the Current Approaches. Int J Mol Sci 2021; 22:ijms22094732. [PMID: 33946969 PMCID: PMC8124143 DOI: 10.3390/ijms22094732] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2021] [Revised: 04/27/2021] [Accepted: 04/28/2021] [Indexed: 12/13/2022] Open
Abstract
The cytogenetic and molecular assessment of deletions, amplifications and rearrangements are key aspects in the diagnosis and therapy of cancer. Not only the initial evaluation and classification of the disease, but also the follow-up of the tumor rely on these laboratory approaches. The therapeutic choice can be guided by the results of the laboratory testing. Genetic deletions and/or amplifications directly affect the susceptibility or the resistance to specific therapies. In an era of personalized medicine, the correct and reliable molecular characterization of the disease, also during the therapeutic path, acquires a pivotal role. Molecular assays like multiplex ligation-dependent probe amplification and droplet digital PCR represent exceptional tools for a sensitive and reliable detection of genetic alterations and deserve a role in molecular oncology. In this manuscript we provide a technical comparison of these two approaches with the golden standard represented by fluorescence in situ hybridization. We also describe some relevant targets currently evaluated with these techniques in solid and hematologic tumors.
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Affiliation(s)
- Vincenza Ylenia Cusenza
- Laboratory of Translational Research, Azienda Unità Sanitaria Locale—IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy;
| | - Alessandra Bisagni
- Pathology Unit, Azienda Unità Sanitaria Locale—IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy;
| | - Monia Rinaldini
- Medical Genetics Unit, Azienda Unità Sanitaria Locale—IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy; (M.R.); (C.C.)
| | - Chiara Cattani
- Medical Genetics Unit, Azienda Unità Sanitaria Locale—IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy; (M.R.); (C.C.)
| | - Raffaele Frazzi
- Laboratory of Translational Research, Azienda Unità Sanitaria Locale—IRCCS di Reggio Emilia, 42122 Reggio Emilia, Italy;
- Correspondence:
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Zhou W, Li J, Lu X, Liu F, An T, Xiao X, Kuo ZC, Wu W, He Y. Derivation and Validation of a Prognostic Model for Cancer Dependency Genes Based on CRISPR-Cas9 in Gastric Adenocarcinoma. Front Oncol 2021; 11:617289. [PMID: 33732644 PMCID: PMC7959733 DOI: 10.3389/fonc.2021.617289] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2020] [Accepted: 01/06/2021] [Indexed: 12/12/2022] Open
Abstract
As a CRISPR-Cas9-based tool to help scientists to investigate gene functions, Cancer Dependency Map genes (CDMs) include an enormous series of loss-of-function screens based on genome-scale RNAi. These genes participate in regulating survival and growth of tumor cells, which suggests their potential as novel therapeutic targets for malignant tumors. By far, studies on the roles of CDMs in gastric adenocarcinoma (GA) are scarce and only a small fraction of CDMs have been investigated. In the present study, datasets of the differentially expressed genes (DEGs) were extracted from the TCGA-based (The Cancer Genome Atlas) GEPIA database, from which differentially expressed CDMs were determined. Functions and prognostic significance of these verified CDMs were evaluated using a series of bioinformatics methods. In all, 246 differentially expressed CDMs were determined, with 147 upregulated and 99 downregulated. Ten CDMs (ALG8, ATRIP, CCT6A, CFDP1, CINP, MED18, METTL1, ORC1, TANGO6, and PWP2) were identified to be prognosis-related and subsequently a prognosis model based on these ten CDMs was constructed. In comparison with that of patients with low risk in TCGA training, testing and GSE84437 cohort, overall survival (OS) of patients with high risk was significantly worse. It was then subsequently demonstrated that for this prognostic model, area under the ROC (receiver operating characteristic) curve was 0.771 and 0.697 for TCGA training and testing cohort respectively, justifying its reliability in predicting survival of GA patients. With the ten identified CDMs, we then constructed a nomogram to generate a clinically practical model. The regulatory networks and functions of the ten CDMs were then explored, the results of which demonstrated that as the gene significantly associated with survival of GA patients and Hazard ratio (HR), PWP2 promoted in-vitro invasion and migration of GA cell lines through the EMT signaling pathway. Therefore, in conclusion, the present study might help understand the prognostic significance and molecular functions of CDMs in GA.
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Affiliation(s)
- Wenjie Zhou
- Digestive Disease Center, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.,Department of Gastrointestinal Surgery, First Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Junqing Li
- Digestive Disease Center, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.,Department of Gastrointestinal Surgery, First Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Xiaofang Lu
- Department of Pathology, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Fangjie Liu
- Department of Hematology, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Tailai An
- Digestive Disease Center, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Xing Xiao
- Scientific Research Centre, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Zi Chong Kuo
- Digestive Disease Center, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Wenhui Wu
- Digestive Disease Center, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Yulong He
- Digestive Disease Center, Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China.,Department of Gastrointestinal Surgery, First Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
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Aberrant Telomere Length in Circulating Cell-Free DNA as Possible Blood Biomarker with High Diagnostic Performance in Endometrial Cancer. Pathol Oncol Res 2020; 26:2281-2289. [PMID: 32462419 DOI: 10.1007/s12253-020-00819-x] [Citation(s) in RCA: 36] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 05/12/2020] [Indexed: 02/07/2023]
Abstract
To investigate the diagnostic performance of relative telomere length (RTL) in cell-free DNA (cfDNA) for endometrioid endometrial cancer (EC). We measured RTL in cfDNA of 40 EC patients (65 ± 12 years) and 31 healthy controls (HC) (63 ± 13 years), excluding in both groups other oncologic and severe non-oncologic diseases to limit confounders. Circulating cfDNA was extracted from serum using the QIAamp DNA Blood Mini kit (Qiagen, Hilden, Germany). After the quantitative real-time polymerase chain reaction, telomere repeat copy number to single-gene copy number ratio was calculated. RTL in cfDNA was found to be significantly lower in EC patients than in HC (p < 0.0001). The diagnostic performance of cfDNA RTL was estimated with receiver operating characteristics (ROC) curve analysis, which showed a diagnostic accuracy for EC of 0.87 (95% CI: 0.79-0.95, p < 0.0001). The cutoff cfDNA RTL value of 2.505 (T/S copy ratio) reported a sensitivity of 80.0% (95% CI: 64.35-90.95) and a specificity of 80.65% (95% CI: 62.53-92.55). Significant differences of RTL among EC stages or grades (p = 0.85 and p = 0.89, respectively) were not observed. Our results suggest that cfDNA RTL analysis may be a diagnostic tool for EC detection since the early stage, whilst its diagnostic performance seems unsatisfactory for cancer progression, staging, and grading. However, further studies are needed to confirm these preliminary findings. In particular, future investigations should focus on high-risk patients (such as those with atypical endometrial hyperplasia) that may benefit from this tool, because TL shortening is not specific for EC and is influenced by other oncologic and non-oncologic diseases.
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Tuaeva NO, Falzone L, Porozov YB, Nosyrev AE, Trukhan VM, Kovatsi L, Spandidos DA, Drakoulis N, Kalogeraki A, Mamoulakis C, Tzanakakis G, Libra M, Tsatsakis A. Translational Application of Circulating DNA in Oncology: Review of the Last Decades Achievements. Cells 2019; 8:E1251. [PMID: 31615102 PMCID: PMC6829588 DOI: 10.3390/cells8101251] [Citation(s) in RCA: 50] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2019] [Revised: 09/30/2019] [Accepted: 10/12/2019] [Indexed: 02/06/2023] Open
Abstract
In recent years, the introduction of new molecular techniques in experimental and clinical settings has allowed researchers and clinicians to propose circulating-tumor DNA (ctDNA) analysis and liquid biopsy as novel promising strategies for the early diagnosis of cancer and for the definition of patients' prognosis. It was widely demonstrated that through the non-invasive analysis of ctDNA, it is possible to identify and characterize the mutational status of tumors while avoiding invasive diagnostic strategies. Although a number of studies on ctDNA in patients' samples significantly contributed to the improvement of oncology practice, some investigations generated conflicting data about the diagnostic and prognostic significance of ctDNA. Hence, to highlight the relevant achievements obtained so far in this field, a clearer description of the current methodologies used, as well as the obtained results, are strongly needed. On these bases, this review discusses the most relevant studies on ctDNA analysis in cancer, as well as the future directions and applications of liquid biopsy. In particular, special attention was paid to the early diagnosis of primary cancer, to the diagnosis of tumors with an unknown primary location, and finally to the prognosis of cancer patients. Furthermore, the current limitations of ctDNA-based approaches and possible strategies to overcome these limitations are presented.
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Affiliation(s)
- Natalia O Tuaeva
- I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia.
| | - Luca Falzone
- Department of Biomedical and Biotechnlogical Sciences, University of Catania, 95123 Catania, Italy.
- Epidemiology Unit, IRCCS Istituto Nazionale Tumori "Fondazione G. Pascale", 80131 Naples, Italy.
| | - Yuri B Porozov
- I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia.
- ITMO University, Saint Petersburg 197101, Russia.
| | - Alexander E Nosyrev
- I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia.
| | - Vladimir M Trukhan
- I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia.
| | - Leda Kovatsi
- Laboratory of Forensic Medicine and Toxicology, School of Medicine, Aristotle University of Thessaloniki, 54248 Thessaloniki, Greece.
| | - Demetrios A Spandidos
- Laboratory of Clinical Virology, Medical School, University of Crete, Heraklion, 70013 Crete, Greece.
| | - Nikolaos Drakoulis
- Research Group of Clinical Pharmacology and Pharmacogenomics, Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, 15771 Zografou, Greece.
| | - Alexandra Kalogeraki
- Department of Pathology-Cytopathology, Medical School, University of Crete, Heraklion, 70013 Crete, Greece.
| | - Charalampos Mamoulakis
- Department of Urology, University General Hospital of Heraklion, University of Crete, Medical School, Heraklion, 70013 Crete, Greece.
| | - George Tzanakakis
- Laboratory of Anatomy-Histology-Embryology, Medical School, University of Crete, Heraklion, 70013 Crete, Greece.
| | - Massimo Libra
- Department of Biomedical and Biotechnlogical Sciences, University of Catania, 95123 Catania, Italy.
- Research Center for Prevention, Diagnosis and Treatment of Cancer, University of Catania, 95123 Catania, Italy.
| | - Aristides Tsatsakis
- I.M. Sechenov First Moscow State Medical University (Sechenov University), 119048 Moscow, Russia.
- Department of Forensic Sciences and Toxicology, Faculty of Medicine, University of Crete, Heraklion, 71003 Crete, Greece.
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