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Han Y, Guo XP, Zhi QM, Xu JJ, Liu F, Kuang YT. Circulating exosomal miR-17-92 cluster serves as a novel noninvasive diagnostic marker for patients with gastric cancer. World J Gastrointest Oncol 2025; 17:104776. [DOI: 10.4251/wjgo.v17.i5.104776] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/31/2024] [Revised: 02/25/2025] [Accepted: 03/13/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Gastric cancer (GC) is among the most common malignant tumors and remains a leading cause of cancer-related mortality worldwide. Furthermore, exosomal miRNAs are regarded as promising noninvasive biomarkers for diagnosing malignant tumors.
AIM To investigate the expression of exosomal miR-17-92 clusters and develop a potential biomarker for GC diagnosis
METHODS Exosomes were isolated from serum samples obtained from 72 GC patients and 20 healthy controls. The isolated exosomes were validated using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. Exosomal RNA was then extracted, and the expression profile of the miR-17-92 cluster was analyzed using qRT-PCR. Statistical methods were employed to evaluate the relationship between the serum exosomal miR-17-92 cluster expression and the clinicopathological parameters of GC patients as well as to assess the diagnostic utility of these miRNAs.
RESULTS The expression of four members of the exosomal miR-17-92 cluster-miR-17, miR-18, miR-19a, and miR-92-was significantly upregulated in the serum samples of patients with GC compared with those of healthy controls. The miR-17-92 cluster panel demonstrated substantially higher clinical diagnostic value for GC than any individual component or pair. Additionally, the expression of traditional tumor biomarkers-carcinoembryonic antigen and carbohydrate antigen 19-9-was significantly elevated in the serum of patients with GC compared with that of healthy controls. Each biomarker, whether alone or in combination, effectively differentiated the patients from healthy controls. Furthermore, a combined panel of the two traditional tumor biomarkers and the four miR-17-92 cluster members exhibited the highest diagnostic accuracy for GC. Elevated miR-17-92 expression was also strongly associated with tumor size, tumor depth, lymph node metastasis, distant metastasis, and tumor-node-metastasis stage.
CONCLUSION Our findings revealed that the circulating exosomal miR-17-92 cluster may be used as a potential noninvasive biomarker to improve diagnostic efficiency for GC.
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Affiliation(s)
- Ye Han
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Xing-Po Guo
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Qiao-Ming Zhi
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Jing-Jing Xu
- Department of Central Laboratory, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Fei Liu
- Department of Gastroenterology, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
| | - Yu-Ting Kuang
- Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215006, Jiangsu Province, China
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2
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Kotsifa E, Saffioti F, Mavroeidis VK. Cholangiocarcinoma: The era of liquid biopsy. World J Gastroenterol 2025; 31:104170. [PMID: 40124277 PMCID: PMC11924015 DOI: 10.3748/wjg.v31.i11.104170] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Revised: 01/28/2025] [Accepted: 02/14/2025] [Indexed: 03/13/2025] Open
Abstract
Cholangiocarcinoma (CCA) is a highly aggressive and heterogeneous malignancy arising from the epithelial cells of the biliary tract. The limitations of the current methods in the diagnosis of CCA highlight the urgent need for new, accurate tools for early cancer detection, better prognostication and patient monitoring. Liquid biopsy (LB) is a modern and non-invasive technique comprising a diverse group of methodologies aiming to detect tumour biomarkers from body fluids. These biomarkers include circulating tumour cells, cell-free DNA, circulating tumour DNA, RNA and extracellular vesicles. The aim of this review is to explore the current and potential future applications of LB in CCA management, with a focus on diagnosis, prognostication and monitoring. We examine both its significant potential and the inevitable limitations associated with this technology. We conclude that LB holds considerable promise, but further research is necessary to fully integrate it into precision oncology for CCA.
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Affiliation(s)
- Evgenia Kotsifa
- The Second Propaedeutic Department of Surgery, National and Kapodistrian University of Athens, General Hospital of Athens “Laiko”, Athens 11527, Greece
| | - Francesca Saffioti
- Department of Gastroenterology and Hepatology, Oxford University Hospitals NHS Foundation Trust, Oxford OX3 9DU, United Kingdom
- University College London Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and University College London, London NW3 2QG, United Kingdom
- Division of Clinical and Molecular Hepatology, Department of Clinical and Experimental Medicine, University Hospital of Messina, Messina 98124, Italy
| | - Vasileios K Mavroeidis
- Department of Transplant Surgery, North Bristol NHS Trust, Southmead Hospital, Bristol BS10 5NB, United Kingdom
- Department of Gastrointestinal Surgery, North Bristol NHS Trust, Southmead Hospital, Bristol BS10 5NB, United Kingdom
- Department of HPB Surgery, Bristol Royal Infirmary, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol BS2 8HW, United Kingdom
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3
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Wang X, Bai L, Kong L, Guo Z. Advances in circulating tumor cells for early detection, prognosis and metastasis reduction in lung cancer. Front Oncol 2024; 14:1411731. [PMID: 38974237 PMCID: PMC11224453 DOI: 10.3389/fonc.2024.1411731] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2024] [Accepted: 06/07/2024] [Indexed: 07/09/2024] Open
Abstract
Globally, lung cancer stands as the leading type of cancer in terms of incidence and is the major source of mortality attributed to cancer. We have outlined the molecular biomarkers for lung cancer that are available clinically. Circulating tumor cells (CTCs) spread from the original location, circulate in the bloodstream, extravasate, and metastasize, forming secondary tumors by invading and establishing a favorable environment. CTC analysis is considered a common liquid biopsy method for lung cancer. We have enumerated both in vivo and ex vivo techniques for CTC separation and enrichment, examined the advantages and limitations of these methods, and also discussed the detection of CTCs in other bodily fluids. We have evaluated the value of CTCs, as well as CTCs in conjunction with other biomarkers, for their utility in the early detection and prognostic assessment of patients with lung cancer. CTCs engage with diverse cells of the metastatic process, interfering with the interaction between CTCs and various cells in metastasis, potentially halting metastasis and enhancing patient prognosis.
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Affiliation(s)
- Xiaochen Wang
- Department of Pathology and Pathophysiology, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China
- Department of Pathology, Cancer Hospital Affiliated to Inner Mongolia Medical University / Peking University Cancer Hospital Inner Mongolia Hospital, Hohhot, Inner Mongolia, China
| | - Lu Bai
- Department of Pathology and Pathophysiology, Inner Mongolia Medical University, Hohhot, Inner Mongolia, China
- Department of Pathology, Cancer Hospital Affiliated to Inner Mongolia Medical University / Peking University Cancer Hospital Inner Mongolia Hospital, Hohhot, Inner Mongolia, China
| | - Linghui Kong
- Department of Pathology, Cancer Hospital Affiliated to Inner Mongolia Medical University / Peking University Cancer Hospital Inner Mongolia Hospital, Hohhot, Inner Mongolia, China
| | - Zhijuan Guo
- Department of Pathology, Cancer Hospital Affiliated to Inner Mongolia Medical University / Peking University Cancer Hospital Inner Mongolia Hospital, Hohhot, Inner Mongolia, China
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4
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Capuozzo M, Ferrara F, Santorsola M, Zovi A, Ottaiano A. Circulating Tumor Cells as Predictive and Prognostic Biomarkers in Solid Tumors. Cells 2023; 12:2590. [PMID: 37998325 PMCID: PMC10670669 DOI: 10.3390/cells12222590] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2023] [Revised: 11/06/2023] [Accepted: 11/07/2023] [Indexed: 11/25/2023] Open
Abstract
Circulating tumor cells (CTCs) have emerged as pivotal biomarkers with significant predictive and prognostic implications in solid tumors. Their presence in peripheral blood offers a non-invasive window into the dynamic landscape of cancer progression and treatment response. This narrative literature review synthesizes the current state of knowledge surrounding the multifaceted role of CTCs in predicting clinical outcomes and informing prognosis across a spectrum of solid tumor malignancies. This review delves into the evolving landscape of CTC-based research, emphasizing their potential as early indicators of disease recurrence, metastatic potential, and therapeutic resistance. Moreover, we have underscored the dynamic nature of CTCs and their implications for personalized medicine. A descriptive and critical analysis of CTC detection methodologies, their clinical relevance, and their associated challenges is also presented, with a focus on recent advancements and emerging technologies. Furthermore, we examine the integration of CTC-based liquid biopsies into clinical practice, highlighting their role in guiding treatment decisions, monitoring treatment efficacy, and facilitating precision oncology. This review highlights the transformative impact of CTCs as predictive and prognostic biomarkers in the management of solid tumors by promoting a deeper understanding of the clinical relevance of CTCs and their role in advancing the field of oncology.
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Affiliation(s)
| | | | - Mariachiara Santorsola
- Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, Via M. Semmola, 80131 Naples, Italy;
| | - Andrea Zovi
- Ministry of Health, Viale Giorgio Ribotta 5, 00144 Rome, Italy;
| | - Alessandro Ottaiano
- Istituto Nazionale Tumori di Napoli, IRCCS “G. Pascale”, Via M. Semmola, 80131 Naples, Italy;
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5
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Kumarasamy G, Mohd Salim NH, Mohd Afandi NS, Hazlami Habib MA, Mat Amin ND, Ismail MN, Musa M. Glycoproteomics-based liquid biopsy: translational outlook for colorectal cancer clinical management in Southeast Asia. Future Oncol 2023; 19:2313-2332. [PMID: 37937446 DOI: 10.2217/fon-2023-0704] [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: 11/09/2023] Open
Abstract
Colorectal cancer (CRC) signifies a significant healthcare challenge in Southeast Asia. Despite advancements in screening approaches and treatment modalities, significant medical gaps remain, ranging from prevention and early diagnosis to determining targeted therapy and establishing personalized approaches to managing CRC. There is a need to expand more validated biomarkers in clinical practice. An advanced technique incorporating high-throughput mass spectrometry as a liquid biopsy to unravel a repertoire of glycoproteins and glycans would potentially drive the development of clinical tools for CRC screening, diagnosis and monitoring, and it can be further adapted to the existing standard-of-care procedure. Therefore this review offers a perspective on glycoproteomics-driven liquid biopsy and its potential integration into the clinical care of CRC in the southeast Asia region.
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Affiliation(s)
- Gaayathri Kumarasamy
- Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Pulau Pinang, 11800, Malaysia
| | - Nurul Hakimah Mohd Salim
- Department of Pathology, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, 16150, Malaysia
| | - Nur Syafiqah Mohd Afandi
- Analytical Biochemistry Research Centre, Universiti Sains Malaysia, Bayan Lepas, Pulau Pinang, 11900, Malaysia
| | - Mohd Afiq Hazlami Habib
- Analytical Biochemistry Research Centre, Universiti Sains Malaysia, Bayan Lepas, Pulau Pinang, 11900, Malaysia
| | - Nor Datiakma Mat Amin
- Analytical Biochemistry Research Centre, Universiti Sains Malaysia, Bayan Lepas, Pulau Pinang, 11900, Malaysia
- Nature Products Division, Forest Research Institute Malaysia, Kepong, Selangor, 52109, Malaysia
| | - Mohd Nazri Ismail
- Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Pulau Pinang, 11800, Malaysia
- Analytical Biochemistry Research Centre, Universiti Sains Malaysia, Bayan Lepas, Pulau Pinang, 11900, Malaysia
| | - Marahaini Musa
- Human Genome Centre, School of Medical Sciences, Universiti Sains Malaysia, Kubang Kerian, Kelantan, 16150, Malaysia
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6
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Qi C, Xiong XZ. Value of peripheral blood circulating tumor cell detection in the diagnosis of thoracic diseases and the prediction of severity. Clin Exp Med 2023; 23:2331-2339. [PMID: 36929453 PMCID: PMC10543157 DOI: 10.1007/s10238-023-01022-3] [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: 01/18/2023] [Accepted: 02/05/2023] [Indexed: 03/18/2023]
Abstract
Circulating tumor cell (CTC) detection, as a noninvasive liquid biopsy method, has been used in the diagnosis, prognostic indication, and monitoring of a variety of cancers. In this study, we aimed to investigate whether CTC detection could be used in the early diagnosis and prediction of severity of thoracic diseases. We enrolled 168 thoracic disease patients, all of whom underwent pathological biopsy. Carcinoembryonic antigen (CEA) and neuron-specific enolase (NSE) measurement was also performed in 146 patients. There were 131 cases of malignant thoracic diseases and 37 cases of benign lesions. We detected CTCs in a 5 ml peripheral blood sample with the CTCBiopsy® system and analyzed the value of CTC count for predicting disease severity. Of 131 patients with a diagnosis of thoracic malignancy, CTCs were found in blood samples from 122 patients. However, only 2 out of 37 patients with benign thoracic disease had no detectable CTCs. There was no significant correlation between CTC count and benign and malignant lesions (P = 0.986). However, among 131 patients who had been diagnosed with malignant lesions, 33 had lymph node metastasis or distant metastasis. The presence of CTCs was significantly correlated with metastasis (P = 0.016 OR = 1.14). The area under the receiver operating characteristic (ROC) curve was 0.625 (95% confidence interval (CI), 0.519 to 0.730 P = 0.032). In addition, with stage IA1 as the cutoff, all patients were further divided into an early-stage group and a late-stage group. CTC count was significantly correlated with disease progression (P = 0.031 OR = 1.11), with an area under the curve (AUC) of 0.599 (95% CI, 0.506-0.692 P = 0.47). The sensitivity and specificity of CTC detection for the diagnosis of disease stage were 72.3% and 45.5%, respectively. In addition, the cutoff of 2.5 CTCs was the same when predicting disease metastasis and staging. Furthermore, the combination of CTC count, demographic characteristics and tumor markers had better predictive significance for disease staging. CTC count can effectively indicate the stages and metastasis of thoracic diseases, but it cannot differentiate benign and malignant diseases.
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Affiliation(s)
- Chang Qi
- Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China
| | - Xian-Zhi Xiong
- Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, Hubei, China.
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7
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Napolitano S, Parikh AR, Henry J, Parseghian CM, Willis J, Raghav KP, Morris VK, Johnson B, Kee BK, Dasari AN, Overman MJ, Luthra R, Drusbosky LM, Corcoran RB, Kopetz S, Sun R. Novel Clinical Tool to Estimate Risk of False-Negative KRAS Mutations in Circulating Tumor DNA Testing. JCO Precis Oncol 2023; 7:e2300228. [PMID: 37824798 DOI: 10.1200/po.23.00228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/29/2023] [Accepted: 08/03/2023] [Indexed: 10/14/2023] Open
Abstract
PURPOSE In metastatic colorectal cancer, the detection of RAS mutations by circulating tumor DNA (ctDNA) has emerged as a valid and noninvasive alternative approach to determining RAS status. However, some RAS mutations may be missed, that is, false negatives can occur, possibly compromising important treatment decisions. We propose a statistical model to assess the probability of false negatives when performing ctDNA testing for RAS. METHODS Cohorts of 172 subjects with tissue and multipanel ctDNA testing from MD Anderson Cancer Center and 146 subjects from Massachusetts General Hospital were collected. We developed a Bayesian model that uses observed frequencies of reference mutations (the maximum of APC and TP53) to provide information about the probability of KRAS false negatives. The model was alternatively trained on one cohort and tested on the other. All data were collected on Guardant assays. RESULTS The model suggests that negative KRAS findings are believable when the maximum of APC and TP53 frequencies is at least 8% (corresponding posterior probability of false negative <5%). Validation studies demonstrated the ability of our tool to discriminate between false-negative and true-negative subjects. Simulations further confirmed the utility of the proposed approach. CONCLUSION We suggest clinicians use the tool to more precisely quantify KRAS false-negative ctDNA results when at least one of the reference mutations (APC, TP53) is observed; usage may be especially important for subjects with a maximum reference frequency of <8%. Extension of the methodology to predict false negatives of other genes is possible. Additional reference genes can also be considered. Use of personal training data sets is supported. An open-source R Shiny application is available for public use.
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Affiliation(s)
- Stefania Napolitano
- Department of Precision Medicine, Università degli Studi della Campania Luigi Vanvitelli, Napoli, Italy
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Aparna R Parikh
- Department of Medicine, Division of Hematology and Oncology, Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA
| | | | - Christine M Parseghian
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Jason Willis
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Kanwal P Raghav
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Van K Morris
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Benny Johnson
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Bryan K Kee
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Arvind N Dasari
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Michael J Overman
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Raja Luthra
- Department of Hematopathology, Division of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX
| | | | | | - Scott Kopetz
- Department of Gastrointestinal Medical Oncology, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX
| | - Ryan Sun
- Department of Biostatistics, Division of Basic Science, The University of Texas MD Anderson Cancer Center, Houston, TX
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Zaky W, Ragoonanan D, Batth I, Dao L, Wang J, Xia X, Daw NC, Gill JB, Khatua S, Li S. Automated Capture and Analysis of Circulating Tumor Cells in Pediatric, Adolescent and Young Adult Patients with Central Nervous System Tumors. Cancers (Basel) 2023; 15:3853. [PMID: 37568669 PMCID: PMC10417345 DOI: 10.3390/cancers15153853] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2023] [Revised: 07/24/2023] [Accepted: 07/26/2023] [Indexed: 08/13/2023] Open
Abstract
Tumors of the central nervous system (CNS) are the most common and lethal childhood malignancy. Detection of residual disease and longitudinal monitoring of treatment response in patients are challenging and rely on serial imaging. This current standard of care fails to detect microscopic disease or provide molecular characteristics of residual tumors. As such, there is dire need for minimally invasive liquid biopsy techniques. We have previously shown the high specificity of using cell surface vimentin (CSV) to identify circulating tumor cells (CTCs) from patients bearing various types of cancers. Here, we describe the first report of CTCs captured from peripheral blood samples in 58 pediatric CNS tumor patients. In this study, we used a CSV-coated cell capture chip, the Abnova CytoQuest automated CTC isolation system, to boost the CTC capture from pediatric patients with CNS tumors. We successfully isolated CTCs in six glioma patients using immunostaining of histone H3 lysine27-to-methionine (H3K27M) mutations which are highly expressed by this tumor. We show that CSV is a viable marker for CNS CTC isolation and that this is a feasible method for detecting microscopic disease. Larger-scale studies focusing on CTCs in pediatric CNS tumors to explore their diagnostic and prognostic value are warranted.
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Affiliation(s)
- Wafik Zaky
- Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77023, USA
| | - Dristhi Ragoonanan
- Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77023, USA
| | - Izhar Batth
- Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77023, USA
| | - Long Dao
- Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77023, USA
| | - Jian Wang
- Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
| | - Xueqing Xia
- Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77023, USA
| | - Najat C. Daw
- Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77023, USA
| | - Jonathan B. Gill
- Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77023, USA
| | - Soumen Khatua
- Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77023, USA
| | - Shulin Li
- Department of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, TX 77023, USA
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9
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Liu F, Wang Y, Gu H, Wang X. Technologies and applications of single-cell DNA methylation sequencing. Theranostics 2023; 13:2439-2454. [PMID: 37215576 PMCID: PMC10196823 DOI: 10.7150/thno.82582] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 04/09/2023] [Indexed: 05/24/2023] Open
Abstract
DNA methylation is the most stable epigenetic modification. In mammals, it usually occurs at the cytosine of CpG dinucleotides. DNA methylation is essential for many physiological and pathological processes. Aberrant DNA methylation has been observed in human diseases, particularly cancer. Notably, conventional DNA methylation profiling technologies require a large amount of DNA, often from a heterogeneous cell population, and provide an average methylation level of many cells. It is often not realistic to collect sufficient numbers of cells, such as rare cells and circulating tumor cells in peripheral blood, for bulk sequencing assays. It is therefore essential to develop sequencing technologies that can accurately profile DNA methylation using small numbers of cells or even single cells. Excitingly, many single-cell DNA methylation sequencing and single-cell omics sequencing technologies have been developed, and applications of these methods have greatly expanded our understanding of the molecular mechanism of DNA methylation. Here, we summaries single-cell DNA methylation and multi-omics sequencing methods, delineate their applications in biomedical sciences, discuss technical challenges, and present our perspective on future research directions.
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Affiliation(s)
- Fang Liu
- Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China
- University of Science and Technology of China, Hefei, 230026, China
- Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, 230031, China
| | - Yunfei Wang
- Zhejiang ShengTing Biotech. Ltd, Hangzhou, 310000, China
| | - Hongcang Gu
- Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei, 230031, China
- University of Science and Technology of China, Hefei, 230026, China
- Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, 230031, China
| | - Xiaoxue Wang
- Department of Hematology, the First Hospital of China Medical University, Shenyang, 110001, China
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10
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Meng Y, Zhang Y, Liu J, Zhao L, Ren Q, Wang F, Li C. Dual-targeting surface-enhancement Raman scattering tags based on silver nanocubes for early diagnosis of pheochromocytoma. Anal Chim Acta 2023; 1256:341148. [PMID: 37037629 DOI: 10.1016/j.aca.2023.341148] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2023] [Revised: 03/24/2023] [Accepted: 03/26/2023] [Indexed: 03/29/2023]
Abstract
Pheochromocytoma (PCC), a rare tumor, often develops distant metastases after diagnosis, delaying early intervention treatment. In order to overcome the limitations of traditional diagnostic methods, dual-targeting Surface-Enhancement Raman Scattering (SERS) cytosensor was developed to identify and detect PCC-CTCs from peripheral blood. Meta-iodobenzylguanidine (MIBG) and octreotide-2,2',2″,2'''- (1,4,7,10 -tetraazacyclododecane-1,4,7,10-tetrayl) tetraacetic acid (DOTA) functionalized magnetic Fe3O4 and Ag-DTNB were prepared as capture probe and signal probe for SERS signal export, respectively. Ag nanocubes (AgNCs) as Raman active substrate offer an enhanced electromagnetic field, which could effectively enhance the signal intensity of DTNB and potentially realize trace analyte detection. The obtained SERS fingerprint spectroscopy possessed the characteristic of high sensitivity and resolution in the concentration range from 3.0-3.0 × 106 cells mL-1, with a detection limit of 1 cell mL-1, which laterally compensated the deficiency of scarce CTCs in peripheral blood. This work provided new insight into PCC-CTCs accurate detection.
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11
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Telekes A, Horváth A. The Role of Cell-Free DNA in Cancer Treatment Decision Making. Cancers (Basel) 2022; 14:6115. [PMID: 36551600 PMCID: PMC9776613 DOI: 10.3390/cancers14246115] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 11/28/2022] [Accepted: 11/30/2022] [Indexed: 12/14/2022] Open
Abstract
The aim of this review is to evaluate the present status of the use of cell-free DNA and its fraction of circulating tumor DNA (ctDNA) because this year July 2022, an ESMO guideline was published regarding the application of ctDNA in patient care. This review is for clinical oncologists to explain the concept, the terms used, the pros and cons of ctDNA; thus, the technical aspects of the different platforms are not reviewed in detail, but we try to help in navigating the current knowledge in liquid biopsy. Since the validated and adequately sensitive ctDNA assays have utility in identifying actionable mutations to direct targeted therapy, ctDNA may be used for this soon in routine clinical practice and in other different areas as well. The cfDNA fragments can be obtained by liquid biopsy and can be used for diagnosis, prognosis, and selecting among treatment options in cancer patients. A great proportion of cfDNA comes from normal cells of the body or from food uptake. Only a small part (<1%) of it is related to tumors, originating from primary tumors, metastatic sites, or circulating tumor cells (CTCs). Soon the data obtained from ctDNA may routinely be used for finding minimal residual disease, detecting relapse, and determining the sites of metastases. It might also be used for deciding appropriate therapy, and/or emerging resistance to the therapy and the data analysis of ctDNA may be combined with imaging or other markers. However, to achieve this goal, further clinical validations are inevitable. As a result, clinicians should be aware of the limitations of the assays. Of course, several open questions are still under research and because of it cfDNA and ctDNA testing are not part of routine care yet.
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Affiliation(s)
- András Telekes
- Omnimed-Etosz, Ltd., 81 Széher Rd., 1021 Budapest, Hungary
- Semmelweis University, 26. Üllői Rd., 1085 Budapest, Hungary
| | - Anna Horváth
- Department of Internal Medicine and Haematology, Semmelweis University, 46. Szentkirályi Rd., 1088 Budapest, Hungary
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12
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Xu CY, Zeng XX, Xu LF, Liu M, Zhang F. Circular RNAs as diagnostic biomarkers for gastric cancer: A comprehensive update from emerging functions to clinical significances. Front Genet 2022; 13:1037120. [PMID: 36386850 PMCID: PMC9650219 DOI: 10.3389/fgene.2022.1037120] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2022] [Accepted: 10/10/2022] [Indexed: 08/30/2023] Open
Abstract
The incidence and mortality of gastric cancer ranks as a fouth leading cause of cancer death worldwide, especially in East Asia. Due to the lack of specific early-stage symptoms, the majority of patients in most developing nations are diagnosed at an advanced stage. Therefore, it is urgent to find more sensitive and reliable biomarkers for gastric cancer screening and diagnosis. Circular RNAs (circRNAs), a novel type of RNAs with covalently closed loops, are becoming a latest hot spot in the field of. In recent years, a great deal of research has demonstrated that abnormal expression of circRNAs was associated with the development of gastric cancer, and suggested that circRNA might serve as a potential biomarker for gastric cancer diagnosis. In this review, we summarize the structural characteristics, formation mechanism and biological function of circRNAs, and elucidate research progress and existing problems in early screening of gastric cancer.
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Affiliation(s)
- Chun-Yi Xu
- Zhejiang Chinese Medical University, Hangzhou, China
- Core Facility, Quzhou People’s Hospital, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, China
| | - Xi-Xi Zeng
- Core Facility, Quzhou People’s Hospital, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, China
- Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China, Quzhou, China
| | - Li-Feng Xu
- Core Facility, Quzhou People’s Hospital, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, China
- Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China, Quzhou, China
| | - Ming Liu
- Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China, Quzhou, China
- The Joint Innovation Center for Engineering in Medicine, Quzhou, China
- University of Electronic Science and Technology of China, Chengdu, China
| | - Feng Zhang
- Core Facility, Quzhou People’s Hospital, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou, China
- Yangtze Delta Region Institute (Quzhou), University of Electronic Science and Technology of China, Quzhou, China
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13
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Qi C, Sun SW, Xiong XZ. From COPD to Lung Cancer: Mechanisms Linking, Diagnosis, Treatment, and Prognosis. Int J Chron Obstruct Pulmon Dis 2022; 17:2603-2621. [PMID: 36274992 PMCID: PMC9586171 DOI: 10.2147/copd.s380732] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 09/30/2022] [Indexed: 11/23/2022] Open
Abstract
Many studies have proved that the pathogenesis of the chronic obstructive pulmonary disease (COPD) and lung cancer is related, and may cause and affect each other to a certain extent. In fact, the change of chronic airway obstruction will continue to have an impact on the screening, treatment, and prognosis of lung cancer.In this comprehensive review, we outlined the links and heterogeneity between COPD and lung cancer and finds that factors such as gene expression and genetic susceptibility, epigenetics, smoking, epithelial mesenchymal transformation (EMT), chronic inflammation, and oxidative stress injury may all play a role in the process. Although the relationship between these two diseases have been largely determined, the methods to prevent lung cancer in COPD patients are still limited. Early diagnosis is still the key to a better prognosis. Thus, it is necessary to establish more intuitive screening evaluation criteria and find suitable biomarkers for lung cancer screening in high-risk populations with COPD. Some studies have indicated that COPD may change the efficacy of anti-tumor therapy by affecting the response of lung cancer patients to immune checkpoint inhibitors (ICIs). And for lung cancer patients with COPD, the standardized management of COPD can improve the prognosis. The treatment of lung cancer patients with COPD is an individualized, comprehensive, and precise process. The development of new targets and new strategies of molecular targeted therapy may be the breakthrough for disease treatment in the future.
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Affiliation(s)
- Chang Qi
- Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Sheng-Wen Sun
- Department of Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China
| | - Xian-Zhi Xiong
- Department of Respiratory and Critical Care Medicine, NHC Key Laboratory of Pulmonary Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China,Correspondence: Xian-Zhi Xiong, Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, People’s Republic of China, Tel/Fax +86 27-85726705, Email
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14
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Hewitt DB, Aziz H, Brown ZJ, Pawlik TM. Role of genetic testing in hepatic, pancreatic, and biliary cancers. Surg Oncol 2022; 44:101844. [PMID: 36116416 DOI: 10.1016/j.suronc.2022.101844] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 08/21/2022] [Accepted: 08/24/2022] [Indexed: 12/24/2022]
Abstract
Hepatic, pancreatic, and biliary (HPB) cancers, including hepatocellular carcinoma (HCC), pancreatic ductal adenocarcinoma (PDAC), and cholangiocarcinoma (CCA) cause a disproportionate amount of the global cancer-related mortality. Despite advances in surgical technique and improved systemic therapies, overall 5-year survival remains dismal, especially for patients with pancreatic and biliary cancer. Historically, systemic therapies for patients with HPB cancers were administered in a "one-size-fits-all" approach due to limited reliable data on efficacy for specific patient populations. However, recent advances in genetic testing techniques have greatly improved our understanding of HPB oncogenesis, shedding light on specific genetic mutations responsible for progression from physiologic cellular regulation to uninhibited cellular replication and invasive cancer. Investigations into the oncogenesis of HPB cancers have revealed multiple actionable genetic variants, as well as increased susceptibilities to currently available systemic therapies. For example, patients with PDAC and a known BRCA mutation are more likely to benefit from FOLFIRINOX or gemcitabine plus cisplatin. While patients with CCA and a IDH1 mutation may benefit from ivosidenib. As a result, many national and societal guidelines now recommend some form of genetic testing in the workup of patients with HPB cancers. We herein review the role of genetic testing in these aggressive cancers including DNA sequencing techniques, clinically relevant mutations, therapeutic implications, and current clinical recommendations.
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Affiliation(s)
- D Brock Hewitt
- Department of Surgery, The Ohio State Wexner Medical Center, Columbus, OH, USA
| | - Hassan Aziz
- Department of Surgery, Tufts University Medical Center, Boston, MA, USA
| | - Zachary J Brown
- Department of Surgery, The Ohio State Wexner Medical Center, Columbus, OH, USA
| | - Timothy M Pawlik
- Department of Surgery, The Ohio State Wexner Medical Center, Columbus, OH, USA.
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15
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Yurttaş NÖ, Eşkazan AE. Clinical Application of Biomarkers for Hematologic Malignancies. Biomark Med 2022. [DOI: 10.2174/9789815040463122010010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Over the last decade, significant advancements have been made in the
molecular mechanisms, diagnostic methods, prognostication, and treatment options in
hematologic malignancies. As the treatment landscape continues to expand,
personalized treatment is much more important.
With the development of new technologies, more sensitive evaluation of residual
disease using flow cytometry and next generation sequencing is possible nowadays.
Although some conventional biomarkers preserve their significance, novel potential
biomarkers accurately detect the mutational landscape of different cancers, and also,
serve as prognostic and predictive biomarkers, which can be used in evaluating therapy
responses and relapses. It is likely that we will be able to offer a more targeted and
risk-adapted therapeutic approach to patients with hematologic malignancies guided by
these potential biomarkers. This chapter summarizes the biomarkers used (or proposed
to be used) in the diagnosis and/or monitoring of hematologic neoplasms.;
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Affiliation(s)
- Nurgül Özgür Yurttaş
- Division of Hematology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine,
Istanbul University-Cerrahpasa, Istanbul, Turkey
| | - Ahmet Emre Eşkazan
- Division of Hematology, Department of Internal Medicine, Cerrahpasa Faculty of Medicine,
Istanbul University-Cerrahpasa, Istanbul, Turkey
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16
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Yin XX, Hadjiloucas S, Zhang Y, Tian Z. MRI radiogenomics for intelligent diagnosis of breast tumors and accurate prediction of neoadjuvant chemotherapy responses-a review. COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE 2022; 214:106510. [PMID: 34852935 DOI: 10.1016/j.cmpb.2021.106510] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 11/01/2021] [Indexed: 06/13/2023]
Abstract
BACKGROUND AND OBJECTIVE This paper aims to overview multidimensional mining algorithms in relation to Magnetic Resonance Imaging (MRI) radiogenomics for computer aided detection and diagnosis of breast tumours. The work also aims to address a new problem in radiogenomics mining: how to combine structural radiomics information with non-structural genomics information for improving the accuracy and efficacy of Neoadjuvant Chemotherapy (NAC). METHODS This requires the automated extraction of parameters from non-structural breast radiomics data, and finding feature vectors with diagnostic value, which then are combined with genomics data. In order to address the problem of weakly labelled tumour images, a Generative Adiversarial Networks (GAN) based deep learning strategy is proposed for the classification of tumour types; this has significant potential for providing accurate real-time identification of tumorous regions from MRI scans. In order to efficiently integrate in a deep learning framework different features from radiogenomics datasets at multiple spatio-temporal resolutions, pyramid structured and multi-scale densely connected U-Nets are proposed. A bidirectional gated recurrent unit (BiGRU) combined with an attention based deep learning approach is also proposed. RESULTS The aim is to accurately predict NAC responses by combining imaging and genomic datasets. The approaches discussed incorporate some of the latest developments in of current signal processing and artificial intelligence and have significant potential in advancing and provide a development platform for future cutting-edge biomedical radiogenomics analysis. CONCLUSIONS The association of genotypic and phenotypic features is at the core of the emergent field of Precision Medicine. It makes use of advances in biomedical big data analysis, which enables the correlation between disease-associated phenotypic characteristics, genetics polymorphism and gene activation to be revealed.
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Affiliation(s)
- Xiao-Xia Yin
- Cyberspace Institute of Advanced Technology, Guangzhou University, Guangzhou 510006, China.
| | - Sillas Hadjiloucas
- Department of Biomedical Engineering, The University of Reading, RG6 6AY, UK
| | - Yanchun Zhang
- Cyberspace Institute of Advanced Technology, Guangzhou University, Guangzhou 510006, China
| | - Zhihong Tian
- Cyberspace Institute of Advanced Technology, Guangzhou University, Guangzhou 510006, China
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17
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Tieng FYF, Abu N, Nasir SN, Lee LH, Ab Mutalib NS. Liquid Biopsy-Based Colorectal Cancer Screening via Surface Markers of Circulating Tumor Cells. Diagnostics (Basel) 2021; 11:2136. [PMID: 34829483 PMCID: PMC8618170 DOI: 10.3390/diagnostics11112136] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Accepted: 11/15/2021] [Indexed: 12/24/2022] Open
Abstract
Colorectal cancer (CRC) is ranked second for cancer-related deaths worldwide with approximately half of the patients being diagnosed at the late stages. The untimely detection of CRC results in advancement to the metastatic stage and nearly 90% of cancer-related deaths. The early detection of CRC is crucial to decrease its overall incidence and mortality rates. The recent introduction of circulating tumor cells (CTCs) has enabled a less invasive sampling method from liquid biopsies, besides revealing key information toward CRC metastasis. The current gold standard for CTC identification is the CellSearch® system (Veridex). This first-generation instrumentation relies on a single cell surface marker (CSM) to capture and count CTCs. Detection of CTCs allows the identification of patients at risk for metastasis, whereas CTC enumeration could improve risk assessment, monitoring of systemic therapy, and detection of therapy resistance in advanced metastatic CRC. In this review, we compared the pros and cons between single CSM-based CTC enrichment techniques and multi-marker-based systems. We also highlighted the challenges faced in the routine implementation of CSM-dependent CTC detection methods in CRC screening, prediction, prognosis, disease monitoring, and therapy selection toward precision medicine, as well as the dwelling on post-CTC analysis and characterization methods.
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Affiliation(s)
- Francis Yew Fu Tieng
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (S.N.N.)
| | - Nadiah Abu
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (S.N.N.)
| | - Siti Nurmi Nasir
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (S.N.N.)
| | - Learn-Han Lee
- Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University of Malaysia, Subang Jaya 47500, Selangor, Malaysia
| | - Nurul-Syakima Ab Mutalib
- UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; (F.Y.F.T.); (N.A.); (S.N.N.)
- Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University of Malaysia, Subang Jaya 47500, Selangor, Malaysia
- Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia
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18
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Kamińska P, Buszka K, Zabel M, Nowicki M, Alix-Panabières C, Budna-Tukan J. Liquid Biopsy in Melanoma: Significance in Diagnostics, Prediction and Treatment Monitoring. Int J Mol Sci 2021; 22:9714. [PMID: 34575876 PMCID: PMC8468624 DOI: 10.3390/ijms22189714] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/28/2021] [Revised: 08/25/2021] [Accepted: 09/06/2021] [Indexed: 02/06/2023] Open
Abstract
Liquid biopsy is a common term referring to circulating tumor cells and other biomarkers, such as circulating tumor DNA (ctDNA) or extracellular vesicles. Liquid biopsy presents a range of clinical advantages, such as the low invasiveness of the blood sample collection and continuous control of the tumor progression. In addition, this approach enables the mechanisms of drug resistance to be determined in various methods of cancer treatment, including immunotherapy. However, in the case of melanoma, the application of liquid biopsy in patient stratification and therapy needs further investigation. This review attempts to collect all of the relevant and recent information about circulating melanoma cells (CMCs) related to the context of malignant melanoma and immunotherapy. Furthermore, the biology of liquid biopsy analytes, including CMCs, ctDNA, mRNA and exosomes, as well as techniques for their detection and isolation, are also described. The available data support the notion that thoughtful selection of biomarkers and technologies for their detection can contribute to the development of precision medicine by increasing the efficacy of cancer diagnostics and treatment.
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Affiliation(s)
- Paula Kamińska
- Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland; (P.K.); (K.B.); (M.N.)
| | - Karolina Buszka
- Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland; (P.K.); (K.B.); (M.N.)
| | - Maciej Zabel
- Department of Anatomy and Histology, Collegium Medicum, University of Zielona Góra, 65-046 Zielona Góra, Poland;
| | - Michał Nowicki
- Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland; (P.K.); (K.B.); (M.N.)
| | - Catherine Alix-Panabières
- Laboratory of Rare Human Circulating Cells (LCCRH), University Medical Centre of Montpellier, 34093 Montpellier, France;
- CREEC/CANECEV, MIVEGEC (CREES), University of Montpellier, CNRS, IRD, 34000 Montpellier, France
| | - Joanna Budna-Tukan
- Department of Histology and Embryology, Poznan University of Medical Sciences, 60-781 Poznan, Poland; (P.K.); (K.B.); (M.N.)
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Viëtor CL, Creemers SG, van Kemenade FJ, van Ginhoven TM, Hofland LJ, Feelders RA. How to Differentiate Benign from Malignant Adrenocortical Tumors? Cancers (Basel) 2021; 13:cancers13174383. [PMID: 34503194 PMCID: PMC8431066 DOI: 10.3390/cancers13174383] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2021] [Revised: 08/18/2021] [Accepted: 08/24/2021] [Indexed: 12/16/2022] Open
Abstract
Simple Summary Adrenocortical carcinoma is a rare cancer with a poor prognosis. Adrenal tumors are, however, commonly identified in clinical practice. Discrimination between benign and malignant adrenal tumors is of great importance to determine the appropriate treatment and follow-up strategy. This review summarizes the current diagnostic strategies and challenges to distinguish benign from malignant adrenal lesions. We will focus both on radiological and biochemical assessments, enabling diagnosis of the adrenal lesion preoperatively, and on histopathological and a wide variety of molecular assessments that can be done after surgical removal of the adrenal lesion. Furthermore, new non-invasive strategies such as liquid biopsies, in which blood samples are used to study circulating tumor cells, tumor DNA and microRNA, will be addressed in this review. Abstract Adrenocortical carcinoma (ACC) is a rare cancer with a poor prognosis. Adrenal incidentalomas are, however, commonly identified in clinical practice. Discrimination between benign and malignant adrenal tumors is of great importance considering the large differences in clinical behavior requiring different strategies. Diagnosis of ACC starts with a thorough physical examination, biochemical evaluation, and imaging. Computed tomography is the first-level imaging modality in adrenal tumors, with tumor size and Hounsfield units being important features for determining malignancy. New developments include the use of urine metabolomics, also enabling discrimination of ACC from adenomas preoperatively. Postoperatively, the Weiss score is used for diagnosis of ACC, consisting of nine histopathological criteria. Due to known limitations as interobserver variability and lack of accuracy in borderline cases, much effort has been put into new tools to diagnose ACC. Novel developments vary from immunohistochemical markers and pathological scores, to markers at the level of DNA, methylome, chromosome, or microRNA. Molecular studies have provided insights into the most promising and most frequent alterations in ACC. The use of liquid biopsies for diagnosis of ACC is studied, although in a small number of patients, requiring further investigation. In this review, current diagnostic modalities and challenges in ACC will be addressed.
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Affiliation(s)
- Charlotte L. Viëtor
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, 3015GD Rotterdam, The Netherlands; (C.L.V.); (T.M.v.G.)
| | - Sara G. Creemers
- Department of Internal Medicine, Division of Endocrinology, Erasmus MC University Medical Center, 3015GD Rotterdam, The Netherlands; (S.G.C.); (L.J.H.)
| | - Folkert J. van Kemenade
- Department of Pathology, Erasmus MC University Medical Center, 3015GD Rotterdam, The Netherlands;
| | - Tessa M. van Ginhoven
- Department of Surgical Oncology and Gastrointestinal Surgery, Erasmus MC Cancer Institute, 3015GD Rotterdam, The Netherlands; (C.L.V.); (T.M.v.G.)
| | - Leo J. Hofland
- Department of Internal Medicine, Division of Endocrinology, Erasmus MC University Medical Center, 3015GD Rotterdam, The Netherlands; (S.G.C.); (L.J.H.)
| | - Richard A. Feelders
- Department of Internal Medicine, Division of Endocrinology, Erasmus MC University Medical Center, 3015GD Rotterdam, The Netherlands; (S.G.C.); (L.J.H.)
- Correspondence:
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20
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Rompianesi G, Di Martino M, Gordon-Weeks A, Montalti R, Troisi R. Liquid biopsy in cholangiocarcinoma: Current status and future perspectives. World J Gastrointest Oncol 2021; 13:332-350. [PMID: 34040697 PMCID: PMC8131901 DOI: 10.4251/wjgo.v13.i5.332] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2021] [Revised: 03/02/2021] [Accepted: 03/31/2021] [Indexed: 02/06/2023] Open
Abstract
Cholangiocarcinoma (CCA) are a heterogeneous group of tumors in terms of aetiology, natural history, morphological subtypes, molecular alterations and management, but all sharing complex diagnosis, management, and poor prognosis. Several mutated genes and epigenetic changes have been detected in CCA, with the potential to identify diagnostic and prognostic biomarkers and therapeutic targets. Accessing tumoral components and genetic material is therefore crucial for the diagnosis, management and selection of targeted therapies; but sampling tumor tissue, when possible, is often risky and difficult to be repeated at different time points. Liquid biopsy (LB) represents a way to overcome these issues and comprises a diverse group of methodologies centering around detection of tumor biomarkers from fluid samples. Compared to the traditional tissue sampling methods LB is less invasive and can be serially repeated, allowing a real-time monitoring of the tumor genetic profile or the response to therapy. In this review, we analysis the current evidence on the possible roles of LB (circulating DNA, circulating RNA, exosomes, cytokines) in the diagnosis and management of patients affected by CCA.
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Affiliation(s)
- Gianluca Rompianesi
- Hepato-Bilio-Pancreatic, Minimally Invasive and Robotic Surgery Unit, Department of Clinical Medicine and Surgery, Federico II University Hospital, Napoli 80131, Italy
| | - Marcello Di Martino
- Hepato-Bilio-Pancreatic Surgery Unit, Department of General and Digestive Surgery, Hospital Universitario La Princesa, Madrid 28006, Spain
| | - Alex Gordon-Weeks
- Nuffield Department of Surgical Sciences, University of Oxford, Oxford OX3 9DU, United Kingdom
| | - Roberto Montalti
- Hepato-Bilio-Pancreatic, Minimally Invasive and Robotic Surgery Unit, Department of Clinical Medicine and Surgery, Federico II University Hospital, Napoli 80131, Italy
| | - Roberto Troisi
- Hepato-Bilio-Pancreatic, Minimally Invasive and Robotic Surgery Unit, Department of Clinical Medicine and Surgery, Federico II University Hospital, Napoli 80131, Italy
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21
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Rodríguez J, Avila J, Rolfo C, Ruíz-Patiño A, Russo A, Ricaurte L, Ordóñez-Reyes C, Arrieta O, Zatarain-Barrón ZL, Recondo G, Cardona AF. When Tissue is an Issue the Liquid Biopsy is Nonissue: A Review. Oncol Ther 2021; 9:89-110. [PMID: 33689160 PMCID: PMC8140006 DOI: 10.1007/s40487-021-00144-6] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2020] [Accepted: 02/11/2021] [Indexed: 02/07/2023] Open
Abstract
Precision medicine has impacted the field of medical oncology by introducing personalized therapies, improving all measurable outcomes. This field, in turn, has expanded to obtaining and analyzing a vast and ever-increasing amount of genomic information. One technique currently applied is the liquid biopsy, which consists of detecting and isolating DNA and exosomes in cancer patients. Newly developed techniques have made it possible to use the liquid biopsy in a wide range of settings. However, challenges regarding the validation of its clinical utility exist because of a lack of standardization across different techniques and tumor types, confounder genomic information, lack of appropriate clinical trial designs, and a non-measured, and therefore not estimated, economic impact on population health. Nowadays, liquid biopsy is not routinely used, but ongoing research is increasing its popularity, and a new era in oncology is developing. Therefore, it is essential to have an in-depth understanding of the liquid biopsy technique. In this review, we summarize the leading techniques and liquid biopsy applications in cancer.
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Affiliation(s)
- July Rodríguez
- Foundation for Clinical and Applied Cancer Research (FICMAC), Bogota, Colombia
- Molecular Oncology and Biology Systems Research Group (Fox-G/ONCOLGroup), Universidad El Bosque, Bogota, Colombia
| | - Jenny Avila
- Foundation for Clinical and Applied Cancer Research (FICMAC), Bogota, Colombia
- Molecular Oncology and Biology Systems Research Group (Fox-G/ONCOLGroup), Universidad El Bosque, Bogota, Colombia
| | - Christian Rolfo
- Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD, USA
| | - Alejandro Ruíz-Patiño
- Foundation for Clinical and Applied Cancer Research (FICMAC), Bogota, Colombia
- Molecular Oncology and Biology Systems Research Group (Fox-G/ONCOLGroup), Universidad El Bosque, Bogota, Colombia
| | - Alessandro Russo
- Medical Oncology Unit A.O. Papardo and Department of Human Pathology, University of Messina, Messina, Italy
| | - Luisa Ricaurte
- Foundation for Clinical and Applied Cancer Research (FICMAC), Bogota, Colombia
- Pathology Department, Mayo Clinic, Rochester, MN, USA
| | | | - Oscar Arrieta
- Thoracic Oncology Unit, Instituto Nacional de Cancerología (INCan), Mexico City, Mexico
| | | | - Gonzalo Recondo
- Thoracic Oncology Section, Centro de Educación Médica e Investigaciones Clínicas (CEMIC), Buenos Aires, Argentina
| | - Andrés F Cardona
- Foundation for Clinical and Applied Cancer Research (FICMAC), Bogota, Colombia.
- Molecular Oncology and Biology Systems Research Group (Fox-G/ONCOLGroup), Universidad El Bosque, Bogota, Colombia.
- Clinical and Traslational Oncology Group, Clinica del Country, Bogota, Colombia.
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22
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Mussi V, Ledda M, Convertino A, Lisi A. Raman Mapping of Biological Systems Interacting with a Disordered Nanostructured Surface: A Simple and Powerful Approach to the Label-Free Analysis of Single DNA Bases. MICROMACHINES 2021; 12:mi12030264. [PMID: 33806524 PMCID: PMC8000830 DOI: 10.3390/mi12030264] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Revised: 02/27/2021] [Accepted: 03/01/2021] [Indexed: 11/16/2022]
Abstract
This article demonstrates the possibility to use a novel powerful approach based on Raman mapping of analyte solutions drop casted on a disordered array of Ag covered silicon nanowires (Ag/SiNWs), to identify the characteristic spectral signal of the four DNA bases, adenine (A), thymine (T), cytosine (C), and guanine (G), at concentration as low as 10 ng/µL, and to study their specific way of interacting with the nanostructured substrate. The results show a distinctive and amplified interaction of guanine, the base that is most susceptible to oxidation, with the nanostructured surface. Our findings explain the recently revealed diverse behaviour of cancer and normal DNA deposited on the same Ag/SiNWs, which is ascribed to mechanical deformation and base lesions present on the oxidised DNA molecule backbone and causes detectable variation in the Raman signal, usable for diagnostic purposes. The notable bio-analytical capability of the presented platform, and its sensitivity to the molecule mechanical conformation at the single-base level, thus provides a new reliable, rapid, label-free DNA diagnostic methodology alternative to more sophisticated and expensive sequencing ones.
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Affiliation(s)
- Valentina Mussi
- Institute for Microelectronics and Microsystems, National Research Council, IMM-CNR, 00133 Rome, Italy;
- Correspondence:
| | - Mario Ledda
- Institute of Translational Pharmacology, National Research Council, IFT-CNR, 00133 Rome, Italy; (M.L.); (A.L.)
| | - Annalisa Convertino
- Institute for Microelectronics and Microsystems, National Research Council, IMM-CNR, 00133 Rome, Italy;
| | - Antonella Lisi
- Institute of Translational Pharmacology, National Research Council, IFT-CNR, 00133 Rome, Italy; (M.L.); (A.L.)
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Gaya A, Crook T, Plowman N, Ranade A, Limaye S, Bhatt A, Page R, Patil R, Fulmali P, Datta V, Kumar P, Patil D, Akolkar D. Evaluation of circulating tumor cell clusters for pan-cancer noninvasive diagnostic triaging. Cancer Cytopathol 2021; 129:226-238. [PMID: 32996712 PMCID: PMC7984349 DOI: 10.1002/cncy.22366] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/03/2020] [Revised: 08/29/2020] [Accepted: 09/08/2020] [Indexed: 12/18/2022]
Abstract
BACKGROUND Histopathologic examination (HPE) of tumor tissue obtained by invasive biopsy is the standard for cancer diagnosis but is resource-intensive and has been associated with procedural risks. The authors demonstrate that immunocytochemistry (ICC) profiling of circulating ensembles of tumor-associated cells (C-ETACs) can noninvasively provide diagnostic guidance in solid organ cancers. METHODS The clinical performance of this approach was tested on blood samples from 30,060 individuals, including 9416 individuals with known cancer; 6725 symptomatic individuals with suspected cancer; and 13,919 asymptomatic individuals with no prior diagnosis of cancer. C-ETACs were harvested from peripheral blood and profiled by ICC for organ-specific and subtype-specific markers relevant to the cancer type. ICC profiles were compared with HPE diagnoses to determine concordance. RESULTS The presence of malignancy was confirmed by the detection of C-ETACs in 91.8% of the 9416 individuals with previously known cancer. Of the 6725 symptomatic individuals, 6025 were diagnosed with cancer, and 700 were diagnosed with benign conditions; C-ETACs were detected in 92.6% of samples from the 6025 individuals with cancer. In a subset of 3509 samples, ICC profiling of C-ETACs for organ-specific and subtype-specific markers was concordant with HPE findings in 93.1% of cases. C-ETACs were undetectable in 95% of samples from the 700 symptomatic individuals who had benign conditions and in 96.3% of samples from the 13,919 asymptomatic individuals. CONCLUSIONS C-ETACs were ubiquitous (>90%) in various cancers and provided diagnostically relevant information in the majority (>90%) of cases. This is the first comprehensive report on the feasibility of ICC profiling of C-ETACs to provide pan-cancer diagnostic guidance with accuracy comparable to that of HPE.
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Affiliation(s)
| | - Timothy Crook
- Department of OncologyBroomsfield HospitalChelmsfordUnited Kingdom
| | - Nicholas Plowman
- Department of Clinical OncologySt Bartholomew's HospitalLondonUnited Kingdom
| | | | - Sewanti Limaye
- Department of Medical OncologyKokilaben Dhirubhai Ambani Hospital and Medical Research InstituteMumbaiIndia
| | - Amit Bhatt
- Department of Medical OncologyAvinash Cancer ClinicPuneIndia
| | - Raymond Page
- Department of BioengineeringWorcester Polytechnic InstituteWorcesterMassachusetts
| | - Revati Patil
- Department of Research and InnovationsDatar Cancer GeneticsNashikIndia
| | - Pradip Fulmali
- Department of Research and InnovationsDatar Cancer GeneticsNashikIndia
| | - Vineet Datta
- Department of Research and InnovationsDatar Cancer GeneticsNashikIndia
| | - Prashant Kumar
- Department of Research and InnovationsDatar Cancer GeneticsNashikIndia
| | - Darshana Patil
- Department of Research and InnovationsDatar Cancer GeneticsNashikIndia
| | - Dadasaheb Akolkar
- Department of Research and InnovationsDatar Cancer GeneticsNashikIndia
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Abonar AA, Ayoub SE, Tagreda IA, Abdelhafez MN, Khamiss MM, Abdelaziz MI, Gaber SN, Amin A, Mohammed SR. Impact Of Cell-Free Plasma DNA In Metastatic And Non-Metastatic Prostate Cancer. Curr Mol Med 2021; 22:67-73. [PMID: 33632098 DOI: 10.2174/1566524021666210225101358] [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: 09/23/2020] [Revised: 12/17/2020] [Accepted: 01/06/2021] [Indexed: 12/24/2022]
Abstract
Increased cell-free DNA (cfDNA) is observed in many diseases such as cancer, myocardial infarction, and autoimmune diseases. It has the ability to alter the receptor cell phenotype, triggering events related to malignant transformation. Our study aims at assessing the use of Cell-free plasma DNA in the diagnosis of metastatic and non-metastatic prostate cancer. The study included 180 subjects who were classified into four groups: Group I (GI) included 50 in perfect health subjects as the control group, Group II (GII) included 40 patients with prostatitis, group III (GIII) included 40 patients with benign prostatic hyperplasia (BPH) and Group IV (GIV) included 50 patients with pre-operative prostate cancer (PC). Evaluation of the plasma level of circulating cell-free DNA by real-time PCR and measurement of total PSA (tPSA) and free to total PSA percent (f/tPSA%) were done for all groups. Our study revealed that the level of tPSA was significantly higher in prostate cancer patients while levels of f/t PSA were found to be significantly lower. The level of cfDNA was significantly higher in prostate cancer patients (399.9±88.6ng/ul) when compared to that of the group I (12.1±1.5ng/ul) (p<0.01), group II (14.7±2.4 ng/ul) (p<0.01), and group III (26.6±45.6 ng/ul) (p<0.01) respectively. There was a statistically significant difference in yields of cfDNA between metastatic and non- metastatic groups (P=0.03) with a higher level in the metastatic group.
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Affiliation(s)
- Abdelraouf A Abonar
- Department of Clinical Pathology, Faculty of Medicine, Al-Azhar University. Egypt
| | - Shymaa E Ayoub
- Department of Biochemistry, Fayoum University, Al Fayoum. Egypt
| | - Ibrahim A Tagreda
- Department of Urology, Faculty of Medicine, Al-Azhar University. Egypt
| | | | - Mohammed M Khamiss
- Department of physiology, Faculty of Medicine, Fayoum University, Al Fayoum. Egypt
| | - Mohamed I Abdelaziz
- Surgical oncology unit, general surgery department, Fayoum University. Egypt
| | - Sylvana N Gaber
- Department of Medical Microbiology and Immunology Faculty of Medicine Fayoum university Al Fayoum. Egypt
| | - Amal Amin
- Department of Medical Microbiology and Immunology Faculty of Medicine Fayoum university Al Fayoum. Egypt
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26
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Liu Y, Yang S, Zhao J, He Z, Ma J, Guo Y, Wang W, Yoshizawa A, Prelaj A, Tiseo M, Normanno N, Van Schil PE, Wang Q, Yang X. Cell-free DNA from cerebrospinal fluid can be used to detect the EGFR mutation status of lung adenocarcinoma patients with central nervous system metastasis. Transl Lung Cancer Res 2021; 10:914-925. [PMID: 33718032 PMCID: PMC7947414 DOI: 10.21037/tlcr-21-62] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Background EGFR tyrosine kinase inhibitors (TKIs) have revolutionized the therapeutic approach for EGFR mutated patients. However, acquired resistance to EGFR-TKI therapy is unavoidable. Repeat biopsy cannot be used, and peripheral blood detection shows a low positive rate in cases of brain-only disease progression. Methods Droplet digital polymerase chain reaction (PCR) (ddPCR) was performed on the plasma and cerebrospinal fluid (CSF) samples of 79 lung adenocarcinoma (LUAD) patients with EGFR mutations and central nervous system (CNS) metastasis. The differences in the EGFR mutation status between the paired plasma and CSF samples were assessed, and the role of CSF testing as a predictor of overall survival was evaluated. Results The CSF of patients with neurological symptoms, EGFR-TKI treatment, or leptomeningeal metastasis (LM) had a significantly higher positive rate of EGFR mutation compared to the plasma samples (P=0.001, P=0.035, P=0.019, respectively). Moreover, EGFR mutation status in CSF was consistent with neurological symptoms and LM (kappa =0.455, P<0.001; kappa =0.508, P<0.001; respectively). For the patients with brain metastasis, EGFR mutation-positive rate in CSF samples was lower than that in plasma samples (28.3% vs. 64.2%, P<0.001), while the patients with LM had the opposite result (84.6% vs. 38.5%, P=0.004). Moreover, patients with EGFR mutation in their CSF experienced worse survival [hazard ratio (HR) =2.93, 95% confidence interval (CI): 1.45–5.92; P=0.003, P adjust <0.0001]. Conclusions The EGFR mutation status of CSF was different from that of plasma and is correlated with patient prognosis. CSF could be helpful in detecting the EGFR mutation status of patients, particularly in cases of LM.
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Affiliation(s)
- Yang Liu
- Department of Radiotherapy, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Sen Yang
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China.,Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Jiuzhou Zhao
- Department of Molecular Pathology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Henan Key Laboratory of Molecular Pathology, Zhengzhou, China
| | - Zhen He
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Jie Ma
- Department of Molecular Pathology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Henan Key Laboratory of Molecular Pathology, Zhengzhou, China
| | - Yongjun Guo
- Department of Molecular Pathology, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Henan Key Laboratory of Molecular Pathology, Zhengzhou, China
| | - Wei Wang
- Henan Medical Association, Zhengzhou, China
| | - Akihiko Yoshizawa
- Department of Diagnostic Pathology, Kyoto University Hospital, Sakyo-ku, Kyoto, Japan
| | - Arsela Prelaj
- Medical Oncology Department, Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy.,Department of Electronics, Information, and Bioengineering, Polytechnic University of Milan, Milan, Italy
| | - Marcello Tiseo
- Department of Medicine and Surgery, University of Parma and Medical Oncology Unit, University Hospital of Parma, Parma, Italy
| | - Nicola Normanno
- Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori-IRCCS-"Fondazione G. Pascale", Naples, Italy
| | - Paul E Van Schil
- Department of Thoracic and Vascular Surgery, University Hospital of Antwerp, Edegem, Belgiu
| | - Qiming Wang
- Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou, China
| | - Xiaopeng Yang
- Department of Neurology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, China
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27
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Singh B, Arora S, D'Souza A, Kale N, Aland G, Bharde A, Quadir M, Calderón M, Chaturvedi P, Khandare J. Chemo-specific designs for the enumeration of circulating tumor cells: advances in liquid biopsy. J Mater Chem B 2021; 9:2946-2978. [PMID: 33480960 DOI: 10.1039/d0tb02574g] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Advanced materials and chemo-specific designs at the nano/micrometer-scale have ensured revolutionary progress in next-generation clinically relevant technologies. For example, isolating a rare population of cells, like circulating tumor cells (CTCs) from the blood amongst billions of other blood cells, is one of the most complex scientific challenges in cancer diagnostics. The chemical tunability for achieving this degree of exceptional specificity for extra-cellular biomarker interactions demands the utility of advanced entities and multistep reactions both in solution and in the insoluble state. Thus, this review delineates the chemo-specific substrates, chemical methods, and structure-activity relationships (SARs) of chemical platforms used for isolation and enumeration of CTCs in advancing the relevance of liquid biopsy in cancer diagnostics and disease management. We highlight the synthesis of cell-specific, tumor biomarker-based, chemo-specific substrates utilizing functionalized linkers through chemistry-based conjugation strategies. The capacity of these nano/micro substrates to enhance the cell interaction specificity and efficiency with the targeted tumor cells is detailed. Furthermore, this review accounts for the importance of CTC capture and other downstream processes involving genotypic and phenotypic CTC analysis in real-time for the detection of the early onset of metastases progression and chemotherapy treatment response, and for monitoring progression free-survival (PFS), disease-free survival (DFS), and eventually overall survival (OS) in cancer patients.
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Affiliation(s)
- Balram Singh
- Actorius Innovations and Research Pvt. Ltd, Pune, 411057, India.
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Bagley SJ, Till J, Abdalla A, Sangha HK, Yee SS, Freedman J, Black TA, Hussain J, Binder ZA, Brem S, Desai AS, O’Rourke DM, Long Q, Nabavizadeh SA, Carpenter EL. Association of plasma cell-free DNA with survival in patients with IDH wild-type glioblastoma. Neurooncol Adv 2021; 3:vdab011. [PMID: 33615225 PMCID: PMC7883768 DOI: 10.1093/noajnl/vdab011] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND We aimed to determine whether plasma cell-free DNA (cfDNA) concentration is associated with survival in patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma (GBM). METHODS Pre-operative and post-chemoradiotherapy blood samples were prospectively collected from patients with newly diagnosed IDH wild-type GBM. Patients underwent surgical resection or biopsy and received adjuvant radiotherapy with concomitant temozolomide. Cell-free DNA (cfDNA) was isolated from plasma and quantified using SYBR Green-based q polymerase chain reaction (qPCR). RESULTS Sixty-two patients were enrolled and categorized into high vs. low cfDNA groups relative to the pre-operative median value (25.2 ng/mL, range 5.7-153.0 ng/mL). High pre-operative cfDNA concentration was associated with inferior PFS (median progression-free survival (PFS), 3.4 vs. 7.7 months; log-rank P = .004; hazard ratio [HR], 2.19; 95% CI, 1.26-3.81) and overall survival (OS) (median OS, 8.0 vs. 13.9 months; log-rank P = .01; HR, 2.43; 95% CI, 1.19-4.95). After adjusting for risk factors, including O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status, pre-operative cfDNA remained independently associated with PFS (HR, 2.70; 95% CI, 1.50-4.83; P = .001) and OS (HR, 2.65; 95% CI, 1.25-5.59; P = .01). Post-hoc analysis of change in cfDNA post-chemoradiotherapy compared to pre-surgery (n = 24) showed increasing cfDNA concentration was associated with worse PFS (median, 2.7 vs. 6.0 months; log-rank P = .003; HR, 4.92; 95% CI, 1.53-15.84) and OS (median, 3.9 vs. 19.4 months; log-rank P < .001; HR, 7.77; 95% CI, 2.17-27.76). CONCLUSIONS cfDNA concentration is a promising prognostic biomarker for patients with IDH wild-type GBM. Plasma cfDNA can be obtained noninvasively and may enable more accurate estimates of survival and effective clinical trial stratification.
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Affiliation(s)
- Stephen J Bagley
- Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Abramson Cancer Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Jacob Till
- Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Aseel Abdalla
- Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Hareena K Sangha
- Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Stephanie S Yee
- Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Jake Freedman
- College of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Taylor A Black
- Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Jasmin Hussain
- Department of Neurosurgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Zev A Binder
- Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Neurosurgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Steven Brem
- Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Neurosurgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Arati S Desai
- Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Abramson Cancer Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Donald M O’Rourke
- Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Neurosurgery, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Qi Long
- Department of Biostatistics, Epidemiology, and Informatics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Seyed Ali Nabavizadeh
- Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Department of Radiology, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
| | - Erica L Carpenter
- Division of Hematology-Oncology, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
- Glioblastoma Translational Center of Excellence, Abramson Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, USA
- Abramson Cancer Center, University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
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Abstract
The goal of precision medicine in an oncology context is to offer individuals and their families the most effective and efficient methods available to screen, diagnose, and plan treatment. Much like the rapidly expanding use of circulating free DNA testing to screen for chromosomal anomalies during pregnancy, circulating tumor DNA (ctDNA) can assess for degraded DNA fragments released into the blood by tumors. Also known as liquid biopsy (LB), this technology has the potential to improve cancer screening and postdiagnosis monitoring, but it can also provide genetic information about evolving tumor characteristics, allowing clinicians to pinpoint the most appropriate treatment options and monitor response in real time. Novel uses for ctDNA are emerging almost daily, and every provider should know at least that earlier diagnosis and more targeted therapy may now be possible for many different cancers because of LB. Patients expect their providers, including nurse practitioners, to have an understanding of genomics and when advances in genomics might directly benefit them. Liquid biopsy techniques have been rapidly adopted by the oncology community, with findings moving quickly into clinical care.
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Exploration of Circulating Tumour Cell (CTC) Biology: A Paradigm Shift in Liquid Biopsy. Indian J Clin Biochem 2020; 36:131-142. [PMID: 33867703 PMCID: PMC7994460 DOI: 10.1007/s12291-020-00923-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Accepted: 09/01/2020] [Indexed: 01/07/2023]
Abstract
Circulating tumour cells (CTCs), are disseminated tumour cells found in the blood in solid tumour malignancies. Identification of CTCs act as emerging tools in the field of the Liquid Biopsy. Majority of the studies focused on detection and enumeration of CTCs due to technological challenges those results from the rarity of CTCs in the blood. Enumeration of CTCs has already proven their value as prognostic as well as predictive biomarkers for disease prognosis. However, recent advances in technology permitted to study the molecular and functional features of CTCs and these features have the potential to change the diagnostic, prognostic and predictive landscape in oncology. In this review, we summarize the paradigm shift in the field of liquid biopsy-based cancer diagnostics using CTC isolation and detection. We have discussed recent advances in the technologies for molecular characterization of CTCs which have aided a shift from CTC enumeration to an in-depth analysis of the CTC genome, transcriptomes, proteins, epigenomes along with various functional features. Finally, as a prognosticating strategy, the potentials of CTCs as a tool of liquid biopsy to predict micrometastasis, monitor prognosis and how to use them as an additional tool for cancer staging has been discussed.
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31
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Luo D, Li C, Wu L, Chen Q. [Advances of Exosomes Extraction and Its Mechanism in Early Diagnosis of Lung Cancer]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2020; 23:999-1006. [PMID: 32752584 PMCID: PMC7679221 DOI: 10.3779/j.issn.1009-3419.2020.101.24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
Abstract
肺癌是世界范围内发病率和死亡率较高的恶性肿瘤之一，严重威胁着国民的生命安全与健康。肺癌的早期诊断是肺癌预防和治疗过程中的关键环节，对肺癌进行早期诊断有利于提高患者的生存率。外泌体(exosomes)与肿瘤的侵袭与转移过程密切相关，在肺癌的发生发展过程中，外泌体发挥着重要的调控作用。近年来，以外泌体为载体的生物标记物成为肺癌强有力的诊断工具。外泌体是一种由细胞分泌的由膜包裹的大小均一、直径约为30 nm-200 nm的脂质双分子层结构小囊泡。外泌体的内容物包含不同类型的核酸和蛋白质，这些核酸和蛋白质来源于其亲本细胞(包括亲本癌细胞)，具有广泛的生理功能，包括参与免疫调节、细胞间联络等。外泌体中的生物大分子物质，如单链RNA、长非编码RNA、微小RNA(microRNA, miRNA)、蛋白质以及脂类，可以为肺癌的早期临床诊断提供有价值的信息。因此，本文就外泌体的来源、结构特点、提取方法、生物学特性和在肺癌早期诊断中的作用研究进展做简要阐述。
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Affiliation(s)
- Dan Luo
- Department of Medical Experimental Center, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan 442008, China.,Hubei University of Medicine, College of Pharmacy, Shiyan 442000, China
| | - Chunlei Li
- Department of Medical Experimental Center, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan 442008, China
| | - Lun Wu
- Department of Medical Experimental Center, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan 442008, China
| | - Qinhua Chen
- Department of Medical Experimental Center, Affiliated Dongfeng Hospital, Hubei University of Medicine, Shiyan 442008, China.,Shenzhen Baoan Authentic Traditional Chinese Medicine Therapy Hospital, Shenzhen 518102, China
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32
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Batth IS, Meng Q, Wang Q, Torres KE, Burks J, Wang J, Gorlick R, Li S. Rare osteosarcoma cell subpopulation protein array and profiling using imaging mass cytometry and bioinformatics analysis. BMC Cancer 2020; 20:715. [PMID: 32736533 PMCID: PMC7395380 DOI: 10.1186/s12885-020-07203-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2019] [Accepted: 07/22/2020] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Single rare cell characterization represents a new scientific front in personalized therapy. Imaging mass cytometry (IMC) may be able to address all these questions by combining the power of MS-CyTOF and microscopy. METHODS We have investigated this IMC method using < 100 to up to 1000 cells from human sarcoma tumor cell lines by incorporating bioinformatics-based t-Distributed Stochastic Neighbor Embedding (t-SNE) analysis of highly multiplexed IMC imaging data. We tested this process on osteosarcoma cell lines TC71, OHS as well as osteosarcoma patient-derived xenograft (PDX) cell lines M31, M36, and M60. We also validated our analysis using sarcoma patient-derived CTCs. RESULTS We successfully identified heterogeneity within individual tumor cell lines, the same PDX cells, and the CTCs from the same patient by detecting multiple protein targets and protein localization. Overall, these data reveal that our t-SNE-based approach can not only identify rare cells within the same cell line or cell population, but also discriminate amongst varied groups to detect similarities and differences. CONCLUSIONS This method helps us make greater inroads towards generating patient-specific CTC fingerprinting that could provide an accurate tumor status from a minimally-invasive liquid biopsy.
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Affiliation(s)
- Izhar S Batth
- Department of Pediatrics-Research, Division of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Qing Meng
- Department of Laboratory Medicine, Division of Pathology and Laboratory Medicine, Houston, USA
| | - Qi Wang
- Department of Bioinformatics and Computational Biology, Division of Science, Houston, USA
| | - Keila E Torres
- Department of Surgical Oncology, Division of Surgery, Houston, USA
| | - Jared Burks
- Department of Leukemia, Division of Cancer Medicine, UT MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Jing Wang
- Department of Bioinformatics and Computational Biology, Division of Science, Houston, USA.
| | - Richard Gorlick
- Department of Pediatrics-Research, Division of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA
| | - Shulin Li
- Department of Pediatrics-Research, Division of Pediatrics, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd, Houston, TX, 77030, USA.
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Kaur P, Campo D, Porras TB, Ring A, Lu J, Chairez Y, Su Y, Kang I, Lang JE. A Pilot Study for the Feasibility of Exome-Sequencing in Circulating Tumor Cells Versus Single Metastatic Biopsies in Breast Cancer. Int J Mol Sci 2020; 21:ijms21144826. [PMID: 32650480 PMCID: PMC7402350 DOI: 10.3390/ijms21144826] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 07/05/2020] [Accepted: 07/06/2020] [Indexed: 11/16/2022] Open
Abstract
The comparison of the landscape of somatic alterations in circulating tumor cells (CTCs) versus metastases is challenging. Here, we comprehensively characterized the somatic landscape in bulk (amplified and non-amplified), spike-in breast cancer cells, CTCs, and metastases from breast cancer patients using whole-exome sequencing (WES). We determined the level of genomic concordance for somatic nucleotide variants (SNVs), copy number alterations (CNAs), and structural variants (SVs). The variant allele fractions (VAFs) of somatic variants were remarkably similar between amplified and non-amplified cell line samples as technical replicates. In clinical samples, a significant fraction of somatic variants had low VAFs in CTCs compared to metastases. The most frequently recurrent gene mutations in clinical samples were associated with an elevated C > T mutational signature. We found complex rearrangement patterns including intra- and inter-chromosomal rearrangements, singleton, and recurrent gene fusions, and tandem duplications. We observed high molecular discordance for somatic alterations between paired samples consistent with marked heterogeneity of the somatic landscape. The most prevalent copy number calls were focal deletion events in CTCs and metastases. Our results demonstrate the feasibility of an integrated workflow for the identification of a complete repertoire of somatic alterations and highlight the intrapatient genomic differences that occur between CTCs and metastases.
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Affiliation(s)
- Pushpinder Kaur
- Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; (P.K.); (Y.S.)
- University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA; (J.L.); (I.K.)
| | - Daniel Campo
- Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089, USA;
| | - Tania B. Porras
- Cancer and Blood Disease Institute, Children Hospital Los Angeles, University of Southern California, Los Angeles, CA 90027, USA;
| | - Alexander Ring
- Department of Oncology and Hematology, UniversitätsSpital Zürich, Rämistrasse 100, 8091 Zürich, Switzerland;
| | - Janice Lu
- University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA; (J.L.); (I.K.)
- Division of Medical Oncology, Department of Medicine and University of Southern California Norris Cancer Center, University of Southern California, Los Angeles, CA 90033, USA
| | - Yvonne Chairez
- Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA;
| | - Yunyun Su
- Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; (P.K.); (Y.S.)
- University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA; (J.L.); (I.K.)
| | - Irene Kang
- University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA; (J.L.); (I.K.)
- Division of Medical Oncology, Department of Medicine and University of Southern California Norris Cancer Center, University of Southern California, Los Angeles, CA 90033, USA
| | - Julie E. Lang
- Department of Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA 90033, USA; (P.K.); (Y.S.)
- University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA; (J.L.); (I.K.)
- Correspondence: ; Tel.: +1-(323)-442-8140
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Chen L, Chen Y, Feng YL, Zhu Y, Wang LQ, Hu S, Cheng P. Tumor circulome in the liquid biopsies for digestive tract cancer diagnosis and prognosis. World J Clin Cases 2020; 8:2066-2080. [PMID: 32548136 PMCID: PMC7281040 DOI: 10.12998/wjcc.v8.i11.2066] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Revised: 04/10/2020] [Accepted: 04/28/2020] [Indexed: 02/05/2023] Open
Abstract
Digestive tract cancer is one of the main diseases that endanger human health. At present, the early diagnosis of digestive tract tumors mainly depends on serology, imaging, endoscopy, and so on. Although tissue specimens are the gold standard for cancer diagnosis, with the rapid development of precision medicine in cancer, the demand for dynamic monitoring of tumor molecular characteristics has increased. Liquid biopsy involves the collection of body fluids via non-invasive approaches, and analyzes biological markers such as circulating tumor cells, circulating tumor DNA, circulating cell-free DNA, microRNAs, and exosomes. In recent years, liquid biopsy has become more and more important in the diagnosis and prognosis of cancer in clinical practice due to its convenience, non-invasiveness, high specificity and it overcomes temporal-spatial heterogeneity. Therefore, this review summarizes the current evidence on liquid biopsies in digestive tract cancers in relation to diagnosis and prognosis.
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Affiliation(s)
- Long Chen
- Department of Radiotherapy, Zhejiang Provincial People’s Hospital, People’s Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
| | - Yu Chen
- Department of Pediatric Surgery, Guangdong Women and Children Hospital, Guangzhou 511400, Guangdong Province, China
| | - Yuan-Ling Feng
- Department of Obstetrics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310052, Zhejiang Province, China
| | - Yan Zhu
- Department of Respiratory, Shulan Hospital, Hangzhou 310004, Zhejiang Province, China
| | - Li-Quan Wang
- Department of Obstetrics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310052, Zhejiang Province, China
| | - Shen Hu
- Department of Obstetrics, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310052, Zhejiang Province, China
| | - Pu Cheng
- Department of Gynecology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310052, Zhejiang Province, China
- Key Laboratory of Tumor Microenvironment and Immune Therapy of Zhejiang Province, Hangzhou 310052, Zhejiang Province, China
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Arshad J, Barreto-Coelho P, Jonczak E, Espejo A, D'Amato G, Trent JC. Identification of Genetic Alterations by Circulating Tumor DNA in Leiomyosarcoma: A Molecular Analysis of 73 Patients. JOURNAL OF IMMUNOTHERAPY AND PRECISION ONCOLOGY 2020; 3:64-68. [PMID: 36751526 PMCID: PMC9179395 DOI: 10.36401/jipo-20-3] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 03/31/2020] [Indexed: 01/20/2023]
Abstract
Background Leiomyosarcoma is a malignant mesenchymal tumor of cells of smooth muscle lineage arising commonly in retroperitoneum, uterus, large veins, and the limbs. The genetics of leiomyosarcomas are complex and there is very limited understanding of common driver mutations. Circulating tumor DNA (ctDNA) offers a rapid and noninvasive method of next-generation sequencing (NGS) that could be used for diagnosis, therapy, and detection of recurrence. Methods ctDNA testing was performed using Guardant360, which detects single nucleotide variants, amplifications, fusions, and specific insertion/deletion mutations in 73 genes using NGS. Results Of 73 patients, 59 were found to have one or more cancer-associated genomic alteration. Forty-five (76%) were female with a median age of 63 (range, 38-87) years. All samples were designated metastatic. The most common alterations were detected in Tp53 (65%), BRAF (13%), CCNE (13%), EGFR (12%), PIK3CA (12%), FGFR1 (10%), RB1(10%), KIT (8%), and PDGFRA (8%). Some of the other alterations included RAF1, ERBB2, MET, PTEN TERT, APC, and NOTCH1. Potentially targetable mutations, by Food and Drug Administration-approved or clinical trials, were found in 24 (40%) of the 73 patients. Four patients (5%) were found to have incidental germline TP53 mutations. Conclusion NGS of ctDNA allows identification of genomic alterations in plasma from patients with leiomyosarcoma. Unfortunately, there is limited activity of current targeted agents in leiomyosarcomas. These results suggest opportunities to develop therapy against TP53, cell cycle, and kinase signaling pathways. Further validation and prospective evaluation is warranted to investigate the clinical utility of ctDNA for patients with leiomyosarcoma.
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Affiliation(s)
- Junaid Arshad
- Department of Medicine, Division of Medical Oncology, Miller School of Medicine, Jackson Memorial Hospital/University of Miami, Miami, FL, USA
| | - Priscila Barreto-Coelho
- Department of Medicine, Division of Internal Medicine, Miller School of Medicine, Jackson Memorial Hospital/University of Miami, Miami, FL, USA
| | - Emily Jonczak
- Department of Medicine, Division of Medical Oncology, Miller School of Medicine, Jackson Memorial Hospital/University of Miami, Miami, FL, USA
| | - Andrea Espejo
- Department of Medicine, Division of Medical Oncology, Miller School of Medicine, Jackson Memorial Hospital/University of Miami, Miami, FL, USA
| | - Gina D'Amato
- Department of Medicine, Division of Medical Oncology, Miller School of Medicine, Jackson Memorial Hospital/University of Miami, Miami, FL, USA
,Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Jonathan C. Trent
- Department of Medicine, Division of Medical Oncology, Miller School of Medicine, Jackson Memorial Hospital/University of Miami, Miami, FL, USA
,Sylvester Comprehensive Cancer Center, Miami, FL, USA
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Rolfo C, Cardona AF, Cristofanilli M, Paz-Ares L, Diaz Mochon JJ, Duran I, Raez LE, Russo A, Lorente JA, Malapelle U, Gil-Bazo I, Jantus-Lewintre E, Pauwels P, Mok T, Serrano MJ. Challenges and opportunities of cfDNA analysis implementation in clinical practice: Perspective of the International Society of Liquid Biopsy (ISLB). Crit Rev Oncol Hematol 2020; 151:102978. [PMID: 32428812 DOI: 10.1016/j.critrevonc.2020.102978] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2020] [Accepted: 04/29/2020] [Indexed: 02/07/2023] Open
Abstract
Precision medicine was born with the development of new diagnostic techniques and targeted drugs, yielding better outcomes in cancer care. With the evolution and increasing sensitivity for detecting oncogenic drivers, liquid biopsies (LBs), specifically cell-free DNA (cfDNA) analysis, have been proposed as a minimally-invasive technique for genomic profiling. Ranging from sequencing techniques to PCR-based methods and other more complex strategies, this approach, currently applicable in some solid tumors with robust evidence, is showing promising opportunities in other cancers. However, difficulties in validating their clinical utility exist within limitation at different levels among several techniques, reporting of the results, lack of appropriate clinical trial designs, and unknown economic impact. One of the aims of the ISLB is to create recommendations to develop reliable and sustainable diagnostic, prognostic and predictive tools using LBs. This paper is addressing these objectives, helping the healthcare providers and scientific community to understand the potential of LB.
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Affiliation(s)
- Christian Rolfo
- Thoracic Oncology Department and Early Phase Clinical Trials Section, School of Medicine, Maryland University, Maryland, USA.
| | - Andrés F Cardona
- Clinical and Translational Oncology Group, Clínica del Country, Bogotá, Colombia; Foundation for Clinical and Applied Cancer Research - FICMAC, Bogotá, Colombia; Molecular Oncology and Biology Systems Research Group (Fox-G), Universidad El Bosque, Bogotá, Colombia
| | - Massimo Cristofanilli
- Department of Medicine, Division of Hematology and Oncology, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, 710 N Fairbanks Court, Suite 8-250A, Chicago, IL, 60611, USA
| | - Luis Paz-Ares
- Hospital Universitario 12 de Octubre, CNIO-H12o Lung Cancer Unit, Universidad Complutense and CIBERONC, Madrid, Spain
| | - Juan Jose Diaz Mochon
- DestiNA Genomica S.L. Parque Tecnológico Ciencias de la Salud (PTS), Avenida de la Innovación 1, Edificio BIC, 18016, Armilla, Granada, Spain; GENYO Centre for Genomics and Oncological Research, Pfizer/University of Granada/Andalusian Regional Government. PTS Granada - Avenida de la Ilustración, 114- 18016, Granada, Spain; Department Medicinal and Organic Chemistry, School of Pharmacy, University of Granada, Campus Cartuja s/n, 18071, Granada, Spain
| | - Ignacio Duran
- Servicio de Oncologia Medica, Medical Oncology Department, Hospital Universitario Marques de Valdecilla, Edificio Sur, 2 Planta, Despacho 277, 39008, Santander, Spain
| | - Luis E Raez
- Memorial Cancer Institute, Memorial Health Care System, Florida International University, Florida, USA
| | - Alessandro Russo
- Thoracic Oncology Department and Early Phase Clinical Trials Section, School of Medicine, Maryland University, Maryland, USA; Medical Oncology Unit A.O. Papardo & Department of Human Pathology, University of Messina, Italy
| | - Jose A Lorente
- Laboratory of Genetic Identification, Department of Legal Medicine, University of Granada, Av. de la Investigación, 11, 18071, Granada, Spain; Centre for Genomics and Oncological Research - GENYO, Pfizer, University of Granada, Andalusian Regional Government, Granada, Spain
| | - Umberto Malapelle
- Department of Public Health, University Federico II of Naples, Naples, Italy
| | - Ignacio Gil-Bazo
- Department of Oncology, Clínica Universidad de Navarra, Pamplona, Navarra, Spain; University of Navarra, Center for Applied Medical Research, Program of Solid Tumors, Pamplona, Navarra, Spain; Idisna, Navarra Institute for Health Research, Pamplona, Navarra, Spain; Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain
| | - Eloisa Jantus-Lewintre
- Molecular Oncology Laboratory, Fundación Investigación, Valencia General University Hospital, Valencia, Spain
| | - Patrick Pauwels
- Center for Oncological Research (CORE), University of Antwerp, & Department of Pathology, Antwerp University Hospital, Edegem, Belgium
| | - Tony Mok
- State Key Laboratory in Oncology in South China, Hong Kong, China
| | - María José Serrano
- Centre for Genomics and Oncological Research - GENYO, Pfizer, University of Granada, Andalusian Regional Government, Granada, Spain; Bio-Health Research Institute (Instituto de Investigación Biosanitaria ibs. GRANADA), Spain; Complejo Hospitalario Universitario Granada (CHUG), Department of Medical Oncology, University of Granada, Granada, Spain.
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Kim J, Sahloul S, Orozaliev A, Do VQ, Pham VS, Martins D, Wei X, Levicky R, Song YA. Microfluidic Electrokinetic Preconcentration Chips: Enhancing the detection of nucleic acids and exosomes. IEEE NANOTECHNOLOGY MAGAZINE 2020. [DOI: 10.1109/mnano.2020.2966064] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022]
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Wei J, Zhao Z, Gao J, Wang Y, Ma L, Meng X, Wang Z. Polyacrylamide/Phytic Acid/Polydopamine Hydrogel as an Efficient Substrate for Electrochemical Enrichment of Circulating Cell-Free DNA from Blood Plasma. ACS OMEGA 2020; 5:5365-5371. [PMID: 32201826 PMCID: PMC7081438 DOI: 10.1021/acsomega.9b04397] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/21/2019] [Accepted: 02/20/2020] [Indexed: 05/26/2023]
Abstract
A facile method has been developed for the rapid and efficient enrichment of DNAs from different media including synthetic single-strand DNAs (ssDNAs) from buffer solutions and cell-free DNAs (cfDNAs) from blood plasma through electric field-driven adsorption and desorption of DNAs by a polyacrylamide/phytic acid/polydopamine (PAAM/PA/PDA) hydrogel. The as-prepared PAAM/PA/PDA hydrogel possesses regular porosity with a large surface area, strong electric field responsiveness/good conductivity, and a rich aromatic structure, which can be used as an ideal adsorbent for DNA enrichment under a positive electric field. The enriched DNAs can be released efficiently when the positive electric field is converted to a negative electric field. The PAAM/PA/PDA hydrogel-based electrochemical method enables the completion of the process of DNA adsorption and release within 5 min and exhibits reasonable enrichment efficiencies and recovery rates of various DNAs. For instance, the high enrichment sensitivity (0.1 pmol L-1) together with the excellent recovery (>75%) of an ssDNA with 78 nucleotides is obtained. Combined with the PCR amplification technique, the practicability of the as-proposed method is demonstrated by the screening of circulating tumor DNAs (ctDNAs) with a BRAFV600E mutation in cfDNAs from the blood plasma samples of patients with papillary thyroid cancer or thyroid nodule and random patients from a clinical laboratory.
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Affiliation(s)
- Jia Wei
- Department
of Thyroid Surgery, The First Hospital of
Jilin University, Changchun, Jilin 130021, P. R. China
| | - Zhen Zhao
- State
Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China
| | - Jiaxue Gao
- State
Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China
| | - Yaoqi Wang
- Department
of Thyroid Surgery, The First Hospital of
Jilin University, Changchun, Jilin 130021, P. R. China
| | - Lina Ma
- State
Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China
| | - Xianying Meng
- Department
of Thyroid Surgery, The First Hospital of
Jilin University, Changchun, Jilin 130021, P. R. China
| | - Zhenxin Wang
- State
Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, P. R. China
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Tang S, Cheng J, Yao Y, Lou C, Wang L, Huang X, Zhang Y. Combination of Four Serum Exosomal MiRNAs as Novel Diagnostic Biomarkers for Early-Stage Gastric Cancer. Front Genet 2020; 11:237. [PMID: 32256526 PMCID: PMC7089961 DOI: 10.3389/fgene.2020.00237] [Citation(s) in RCA: 50] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Accepted: 02/27/2020] [Indexed: 12/24/2022] Open
Abstract
Gastric cancer (GC) remains a leading cause of cancer-related mortality in the United States and China, there is an urgent need to discover novel non-invasive biomarkers for the early diagnosis of GC to improve the prognosis of GC patients. Exosomal miRNAs are considered promising biomarkers for cancer diagnosis. Using next-generation sequencing (NGS), bioinformatics and further validation, we identified and evaluated exosomal miRNAs in serum as early diagnostic markers for GC. NGS revealed that the average mappable reads in the RNA libraries were about 6.5 million per patient including miRNAs (73.38%), rRNAs (17.10%), snRNAs (8.83%), snoRNAs (0.65%), and tRNAs (0.04%). A total of 66 up and 13 down-regulated exosomal miRNAs were found in the screened cohort. In the validation cohort, by comparing with healthy individuals, higher levels of serum exosomal miR-92b-3p, let-7g-5p, miR-146b-5p, and miR-9-5p were found to be significantly associated with early-stage GC (p < 0.05). Diagnostic power of the combined panels of the exosomal miRNAs or the combination of exosomal miRNAs and CEA outperformed that of single exosomal miRNA marker for establishing a diagnosis of early-stage GC. The combined diagnosis of exosomal miR-92b-3p + let-7g-5p + miR-146b-5p + miR-9-5p with CEA had the most powerful efficiency with an AUC up to 0.786. In addition, serum levels of exosomal miR-92b-3p were significantly associated with poor cohesiveness (p = 0.0021), let-7g-5p and miR-146b-5p were significantly correlated with nerve infiltration (p = 0.0234 and p = 0.0126, respectively), and miR146b-5p was statistically correlated with tumor invasion depth in early-stage GC (p = 0.0089). In conclusion, serum exosomal miR-92b-3p, -146b-5p, -9-5p, and let-7g-5p may serve as potential non-invasive biomarkers for early diagnosis of GC.
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Affiliation(s)
- Shuli Tang
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.,Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
| | - Jianan Cheng
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.,Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
| | - Yuanfei Yao
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.,Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
| | - Changjie Lou
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China
| | - Liang Wang
- Department of Tumor Biology, H. Lee Moffitt Cancer Center, Tampa, FL, United States
| | - Xiaoyi Huang
- Biotherapy Center, Harbin Medical University Cancer Hospital, Harbin, China
| | - Yanqiao Zhang
- Department of Gastrointestinal Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.,Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China
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Costa C, Dávila-Ibáñez AB. Methodology for the Isolation and Analysis of CTCs. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2020; 1220:45-59. [PMID: 32304079 DOI: 10.1007/978-3-030-35805-1_4] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The majority of deaths related to breast cancer are caused by metastasis. Understanding the process of metastasis is key to achieve a reduction on breast cancer mortality. Currently, liquid biopsies are gaining attention in this regard. Circulating tumor cells (CTCs), an important component of liquid biopsies, are cells shed from primary tumor that disseminate to blood circulation being responsible of distal metastasis. Hence, the study CTCs is a promising alternative to monitor the progress of metastasis disease and can be used for early diagnosis of cancers as well as for earlier assessment of cancer recurrence and therapy efficacy. Despite their clinical interest, CTC analysis is not recommended by oncology guidelines so far. The main reason is that there is no gold standard technology for CTCs isolation and most of the current technologies are not yet validated for clinical use. In this chapter we will focus on the most relevant technologies for CTC isolation based on their properties and depending on whether it is a positive or negative selection. We also describe each technology based on its potential use and its relevance in breast cancer. The chapter also contains a future perspective including the challenges and requirements of CTC detection.
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Affiliation(s)
- Clotilde Costa
- Roche-Chus Joint Unit, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain. .,Centro de Investigación Biomédica en Red Cáncer (CIBERONC), Madrid, Spain.
| | - Ana B Dávila-Ibáñez
- Roche-Chus Joint Unit, Translational Medical Oncology Group (Oncomet), Health Research Institute of Santiago de Compostela, Santiago de Compostela, Spain.
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Yu D, Liu Z, Su C, Han Y, Duan X, Zhang R, Liu X, Yang Y, Xu S. Copy number variation in plasma as a tool for lung cancer prediction using Extreme Gradient Boosting (XGBoost) classifier. Thorac Cancer 2019; 11:95-102. [PMID: 31694073 PMCID: PMC6938748 DOI: 10.1111/1759-7714.13204] [Citation(s) in RCA: 37] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 09/05/2019] [Accepted: 09/05/2019] [Indexed: 01/21/2023] Open
Abstract
Background The main cause of cancer death is lung cancer (LC) which usually presents at an advanced stage, but its early detection would increase the benefits of treatment. Blood is particularly favored in clinical research given the possibility of using it for relatively noninvasive analyses. Copy number variation (CNV) is a common genetic change in tumor genomes, and many studies have indicated that CNV‐derived cell‐free DNA (cfDNA) from plasma could be feasible as a biomarker for cancer diagnosis. Methods In this study, we determined the possibility of using chromosomal arm‐level CNV from cfDNA as a biomarker for lung cancer diagnosis in a small cohort of 40 patients and 41 healthy controls. Arm‐level CNV distributions were analyzed based on z score, and the machine‐learning algorithm Extreme Gradient Boosting (XGBoost) was applied for cancer prediction. Results The results showed that amplifications tended to emerge on chromosomes 3q, 8q, 12p, and 7q. Deletions were frequently detected on chromosomes 22q, 3p, 5q, 16q, 10q, and 15q. Upon applying a trained XGBoost classifier, specificity and sensitivity of 100% were finally achieved in the test group (12 patients and 13 healthy controls). In addition, five‐fold cross‐validation proved the stability of the model. Finally, our results suggested that the integration of four arm‐level CNVs and the concentration of cfDNA into the trained XGBoost classifier provides a potential method for detecting lung cancer. Conclusion Our results suggested that the integration of four arm‐level CNVs and the concentration from of cfDNA integrated withinto the trained XGBoost classifier could become provides a potentially method for detecting lung cancer detection. Key points Significant findings of the study:
Healthy individuals have different arm‐level CNV profiles from cancer patients. Amplifications tend to emerge on chromosome 3q, 8q, 12p, 7q and deletions tend to emerge on chromosome 22q, 3p, 5q, 16q, 10q, 15q. What this study adds:
CfDNA concentration, arm 10q, 3q, 8q, 3p, and 22q are key features for prediction. Trained XGBoost classifier is a potential method for lung cancer detection.
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Affiliation(s)
- Daping Yu
- Thoracic Surgery Department, Beijing Chest Hospital, Capital Medical University; Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Zhidong Liu
- Thoracic Surgery Department, Beijing Chest Hospital, Capital Medical University; Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Chongyu Su
- Thoracic Surgery Department, Beijing Chest Hospital, Capital Medical University; Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Yi Han
- Thoracic Surgery Department, Beijing Chest Hospital, Capital Medical University; Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - XinChun Duan
- Thoracic Surgery Department, Beijing Chest Hospital, Capital Medical University; Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | - Rui Zhang
- Thoracic Surgery Department, Beijing Chest Hospital, Capital Medical University; Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
| | | | - Yang Yang
- Beijing Gencode Diagnostics Laboratory, Beijing, China
| | - Shaofa Xu
- Thoracic Surgery Department, Beijing Chest Hospital, Capital Medical University; Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, China
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Batth IS, Mitra A, Rood S, Kopetz S, Menter D, Li S. CTC analysis: an update on technological progress. Transl Res 2019; 212:14-25. [PMID: 31348892 PMCID: PMC6755047 DOI: 10.1016/j.trsl.2019.07.003] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/20/2019] [Revised: 05/21/2019] [Accepted: 07/09/2019] [Indexed: 12/28/2022]
Abstract
There is a growing need for a more accurate, real-time assessment of tumor status and the probability of metastasis, relapse, or response to treatment. Conventional means of assessment include imaging and tissue biopsies that can be highly invasive, may not provide complete information of the disease's heterogeneity, and not ideal for repeat analysis. Therefore, a less-invasive means of acquiring similar information at greater time points is necessary. Liquid biopsies are samples of a patients' peripheral blood and hold potential of addressing these criteria. Ongoing research has revealed that a tumor can release circulating cells, genetic materials (DNA or RNA), and exosomes into circulation. These potential biomarkers can be captured in a liquid biopsy and analyzed to determine disease status. To achieve these goals, numerous technologies have been developed. In this review, we discuss both prominent and newly developed technologies for circulating tumor cell capture and analysis and their clinical impact.
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Affiliation(s)
- Izhar S Batth
- Department of Pediatrics - Research, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | - Abhisek Mitra
- Department of Pediatrics - Research, The University of Texas MD Anderson Cancer Center, Houston, Texas
| | | | - Scott Kopetz
- Department of Gastrointestinal (GI) Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
| | - David Menter
- Department of Gastrointestinal (GI) Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
| | - Shulin Li
- Department of Pediatrics - Research, The University of Texas MD Anderson Cancer Center, Houston, Texas.
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Sanchez A, Bocklage T. Precision cytopathology: expanding opportunities for biomarker testing in cytopathology. J Am Soc Cytopathol 2019; 8:95-115. [PMID: 31287426 DOI: 10.1016/j.jasc.2018.12.003] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Revised: 12/14/2018] [Accepted: 12/15/2018] [Indexed: 06/09/2023]
Abstract
Precision cytopathology refers to therapeutically linked biomarker testing in cytopatology, a dynamically growing area of the discipline. This review describes basic steps to expand precision cytopathology services. Focusing exclusively on solid tumors, the review is divided into four sections: Section 1: Overview of precision pathology- opportunities and challenges; Section 2: Basic steps in establishing or expanding a precision cytopathology laboratory; Section 3: Cytopathology specimens suitable for next generation sequencing platforms; and Section 4: Summary. precision cytopathology continues to rapidly evolve in parallel with expanding targeted therapy options. Biomarker assays (companion diagnostics) comprise a multitude of test types including immunohistochemistry, in situ hybridization and molecular genetic tests such as PCR and next generation sequencing all of which are performable on cytology specimens. Best practices for precision cytopathology will incorporate traditional diagnostic approaches allied with careful specimen triage to enable successful biomarker analysis. Beyond triaging, cytopathologists knowledgeable about molecular test options and capabilities have the opportunity to refine diagnoses, prognoses and predictive information thereby assuming a lead role in precision oncology biomarker testing.
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Affiliation(s)
| | - Thèrése Bocklage
- Department of Pathology and Laboratory Medicine, University of Kentucky College of Medicine, MS.
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44
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Yang YJ, Kong YY, Li GX, Wang Y, Ye DW, Dai B. Phenotypes of circulating tumour cells predict time to castration resistance in metastatic castration-sensitive prostate cancer. BJU Int 2019; 124:258-267. [PMID: 30536520 DOI: 10.1111/bju.14642] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES To identify biomarkers that predict the response to standard androgen deprivation therapy (ADT) of patients newly diagnosed with metastatic castration-sensitive prostate cancer (CSPC) in order to improve therapeutic decision-making, and to investigate whether the characterization of baseline circulating tumour cells (CTCs) would predict the effective period of standard ADT. MATERIALS AND METHODS The study included 108 patients newly diagnosed with high-volume metastatic CSPC. Enumeration and characterization of patients' baseline CTCs (CTCs+ and CTCs-, indicating detectable and undetectable CTCs, respectively) were performed using the CanPatrol technique, which detects markers of the epithelial to mesenchymal transition (EMT) in CTCs, and classifies CTCs into epithelial, biophenotypic and mesenchymal phenotypes. RESULTS After a median follow-up of 24 months, 90 patients (83.3%) progressed to castration-resistant prostate cancer (CRPC), 93 patients (86.1%) had detectable CTCs, and the median number of CTCs was 4. The rate of progression to CRPC was significantly higher for patients with mesenchymal CTCs+ than for patients with CTCs+/mesenchymal CTCs- and CTCs- (93.1% vs 71.4% and 73.3%; P = 0.013). The median time to CRPC for patients with mesenchymal CTCs+ was significantly shorter than for those with CTCs+/mesenchymal CTCs- and CTCs- (10.5 months vs 18.0 and 14.0 months; P = 0.003). Multivariate Cox regression analysis suggested that the CTC phenotype was the only independent prognostic factor influencing the progression of disease from CSPC to CRPC. CONCLUSIONS Characterization of baseline CTCs according to the EMT phenotype predicted the effective period of standard ADT for patients newly diagnosed with metastatic CSPC. These findings are important for counselling patients and designing clinical trials.
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Affiliation(s)
- Yun-Jie Yang
- Department of Urology, Fudan University Shanghai Cancer Centre, Shanghai, China.,Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
| | - Yun-Yi Kong
- Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China.,Department of Pathology, Fudan University Shanghai Cancer Centre, Shanghai, China
| | - Gao-Xiang Li
- Department of Urology, Fudan University Shanghai Cancer Centre, Shanghai, China.,Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
| | - Yue Wang
- Department of Urology, Fudan University Shanghai Cancer Centre, Shanghai, China.,Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
| | - Ding-Wei Ye
- Department of Urology, Fudan University Shanghai Cancer Centre, Shanghai, China.,Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
| | - Bo Dai
- Department of Urology, Fudan University Shanghai Cancer Centre, Shanghai, China.,Department of Oncology, Fudan University Shanghai Medical College, Shanghai, China
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45
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Corsini LR, Fanale D, Passiglia F, Incorvaia L, Gennusa V, Bazan V, Russo A. Monoclonal antibodies for the treatment of non-hematological tumors: a safety review. Expert Opin Drug Saf 2018; 17:1197-1209. [PMID: 30457416 DOI: 10.1080/14740338.2018.1550068] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: The introduction of monoclonal antibodies (moAbs) into clinical practice revolutionized the treatment strategies in several solid tumors. These agents differ from cytotoxic chemotherapy for their mechanism of action and toxicity. By targeting specific antigens present on healthy cells and modulating immune system activity, these biological drugs are able to generate a wide spectrum of peculiar adverse events that can negatively impact on patients' quality of life. Areas covered: In this review, the main side effects associated with the use of moAbs have been described to show their incidence and current management strategies, which may drive clinicians in their daily practice. Expert opinion: The majority of these drugs represents an example of successful innovation, since they are able to induce a significant improvement of patients' survival and quality of life without any increase in related side effects as compared to standard cancer treatments. For this reason, they have become new milestones in personalized therapy for different non-hematological malignancies. With the increasing use of moAbs in treatment regimens, it is strongly recommended that clinicians are knowledgeable about the side effects associated with these agents, their management and monitoring, to optimize the clinical treatment of cancer patients.
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Affiliation(s)
- Lidia Rita Corsini
- a Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology , University of Palermo , Palermo , Italy
| | - Daniele Fanale
- a Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology , University of Palermo , Palermo , Italy
| | - Francesco Passiglia
- a Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology , University of Palermo , Palermo , Italy
| | - Lorena Incorvaia
- a Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology , University of Palermo , Palermo , Italy
| | - Vincenzo Gennusa
- a Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology , University of Palermo , Palermo , Italy
| | - Viviana Bazan
- a Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology , University of Palermo , Palermo , Italy
| | - Antonio Russo
- a Department of Surgical, Oncological and Oral Sciences, Section of Medical Oncology , University of Palermo , Palermo , Italy
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CORR Insights®: Micrometastatic Drug Screening Platform Shows Heterogeneous Response to MAP Chemotherapy in Osteosarcoma Cell Lines. Clin Orthop Relat Res 2018; 476:1412-1414. [PMID: 29889114 PMCID: PMC6437573 DOI: 10.1097/01.blo.0000540061.16243.f9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
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47
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Burz C, Pop VV, Buiga R, Daniel S, Samasca G, Aldea C, Lupan I. Circulating tumor cells in clinical research and monitoring patients with colorectal cancer. Oncotarget 2018; 9:24561-24571. [PMID: 29849961 PMCID: PMC5966258 DOI: 10.18632/oncotarget.25337] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2017] [Accepted: 04/24/2018] [Indexed: 12/12/2022] Open
Abstract
Colorectal cancer remains a frequent disease to which screening and target therapy exist, but despite this is still marked by a high mortality rate. Even though radical surgery may be performed in many cases, patients relapse with metastatic disease. Circulating tumor cells were incriminated for tumor recurrence, that's why vigorous research started on their field. Owning prognostic and predictive value, it was revealed their usefulness in disease monitoring. Moreover, they may serve as liquid biopsies for genetic tests in cases where tissue biopsy is contraindicated or cannot be performed. In spite of these advantages, they were not included in clinical guidelines, despite CellSearch and many other detection methods were developed to ease the identification of circulating tumor cells. This review highlights the implication of circulating tumor cells in metastasis cascade, intrinsic tumor cells mechanisms and correlations with clinical parameters along with their utility for medical practice and detection techniques.
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Affiliation(s)
- Claudia Burz
- Iuliu Hatieganu University of Medicine and Pharmacy, Department Of Immunology and Allergology, Cluj-Napoca, Romania.,Ion Chiricuta Institute of Oncology, Cluj-Napoca, Romania
| | - Vlad-Vasile Pop
- Iuliu Hatieganu University of Medicine and Pharmacy, Department Of Immunology and Allergology, Cluj-Napoca, Romania
| | - Rares Buiga
- Ion Chiricuta Institute of Oncology, Cluj-Napoca, Romania
| | - Sur Daniel
- Iuliu Hatieganu University of Medicine and Pharmacy, Department Of Immunology and Allergology, Cluj-Napoca, Romania.,Ion Chiricuta Institute of Oncology, Cluj-Napoca, Romania
| | - Gabriel Samasca
- Iuliu Hatieganu University of Medicine and Pharmacy, Department Of Immunology and Allergology, Cluj-Napoca, Romania.,Emergency Hospital for Children, Cluj-Napoca, Romania
| | - Cornel Aldea
- Emergency Hospital for Children, Cluj-Napoca, Romania
| | - Iulia Lupan
- Babeş-Bolyai University, Department of Molecular Biology and Biotehnology, Cluj-Napoca, Romania.,Institute of Interdisciplinary Research in Bio-Nano-Sciences, Cluj-Napoca, Romania
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48
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Armignacco R, Cantini G, Canu L, Poli G, Ercolino T, Mannelli M, Luconi M. Adrenocortical carcinoma: the dawn of a new era of genomic and molecular biology analysis. J Endocrinol Invest 2018; 41:499-507. [PMID: 29080966 DOI: 10.1007/s40618-017-0775-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2017] [Accepted: 09/29/2017] [Indexed: 01/04/2023]
Abstract
Over the last decade, the development of novel and high penetrance genomic approaches to analyze biological samples has provided very new insights in the comprehension of the molecular biology and genetics of tumors. The use of these techniques, consisting of exome sequencing, transcriptome, miRNome, chromosome alteration, genome, and epigenome analysis, has also been successfully applied to adrenocortical carcinoma (ACC). In fact, the analysis of large cohorts of patients allowed the stratification of ACC with different patterns of molecular alterations, associated with different outcomes, thus providing a novel molecular classification of the malignancy to be associated with the classical pathological analysis. Improving our knowledge about ACC molecular features will result not only in a better diagnostic and prognostic accuracy, but also in the identification of more specific therapeutic targets for the development of more effective pharmacological anti-cancer approaches. In particular, the specific molecular alteration profiles identified in ACC may represent targetable events by the use of already developed or newly designed drugs enabling a better and more efficacious management of the ACC patient in the context of new frontiers of personalized precision medicine.
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Affiliation(s)
- R Armignacco
- Endocrinology Unit, Department of Clinical and Experimental Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy
| | - G Cantini
- Endocrinology Unit, Department of Clinical and Experimental Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy
| | - L Canu
- Endocrinology Unit, Department of Clinical and Experimental Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy
| | - G Poli
- Endocrinology Unit, Department of Clinical and Experimental Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy
| | - T Ercolino
- Endocrinology Unit, Department of Clinical and Experimental Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy
| | - M Mannelli
- Endocrinology Unit, Department of Clinical and Experimental Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy
| | - M Luconi
- Endocrinology Unit, Department of Clinical and Experimental Biomedical Sciences "Mario Serio", University of Florence, Viale Pieraccini, 6, 50139, Florence, Italy.
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Lalli E, Luconi M. The next step: mechanisms driving adrenocortical carcinoma metastasis. Endocr Relat Cancer 2018; 25:R31-R48. [PMID: 29142005 DOI: 10.1530/erc-17-0440] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/13/2017] [Accepted: 11/15/2017] [Indexed: 12/20/2022]
Abstract
Endocrine tumors have the peculiarity to become clinically evident not only due to symptoms related to space occupation by the growing lesion, similarly to most other tumors, but also, and most often, because of their specific hormonal secretion, which significantly contributes to their pathological burden. Malignant endocrine tumors, in addition, have the ability to produce distant metastases. Here, we critically review the current knowledge about mechanisms and biomarkers characterizing the metastatic process in adrenocortical carcinoma (ACC), a rare endocrine malignancy with a high risk of relapse and metastatization even when the primary tumor is diagnosed and surgically removed at an early stage. We highlight perspectives of future research in the domain and possible new therapeutic avenues based on targeting factors having an important role in the metastatic process of ACC.
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Affiliation(s)
- Enzo Lalli
- Université Côte d'AzurValbonne, France
- CNRS UMR7275Valbonne, France
- NEOGENEX CNRS International Associated LaboratoryValbonne, France
- Institut de Pharmacologie Moléculaire et CellulaireValbonne, France
| | - Michaela Luconi
- Department of Experimental and Clinical Biomedical Sciences 'Mario Serio'University of Florence, Florence, Italy
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50
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Moon DH, Lindsay DP, Hong S, Wang AZ. Clinical indications for, and the future of, circulating tumor cells. Adv Drug Deliv Rev 2018; 125:143-150. [PMID: 29626548 DOI: 10.1016/j.addr.2018.04.002] [Citation(s) in RCA: 54] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2017] [Revised: 03/14/2018] [Accepted: 04/02/2018] [Indexed: 12/16/2022]
Abstract
Circulating tumor cells (CTCs) are cells that have detached from the primary tumor and entered circulation with potential to initiate a site of metastasis. Currently, CTC detection using CellSearch is cleared by the Food and Drug Administration for monitoring metastatic breast, prostate, and colorectal cancers as a prognostic biomarker for progression-free and overall survival. Accumulating evidence suggests CTCs have similar prognostic value in other metastatic and non-metastatic settings. Current research efforts are focused on extending the utility of CTCs beyond a prognostic biomarker to help guide clinical decision-making. These include using CTCs as a screening tool for diagnosis, liquid biopsy for molecular profiling, predictive biomarker to specific therapies, and monitoring tool to assess response and guide changes to treatment. CTCs have unique advantages vs circulating tumor DNA in this endeavor. Indications for CTCs in daily practice will expand as isolation techniques improve and clinical studies validating their utility continue to grow.
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Affiliation(s)
- Dominic H Moon
- Department of Radiation Oncology, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27599, USA
| | - Daniel P Lindsay
- Department of Radiation Oncology, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27599, USA
| | - Seungpyo Hong
- Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin, 777 Highland Ave, Madison, WI 53705, USA; Yonsei Frontier Lab, Yonsei University, Seoul 03722, Republic of Korea
| | - Andrew Z Wang
- Department of Radiation Oncology, University of North Carolina at Chapel Hill, 101 Manning Drive, Chapel Hill, NC 27599, USA.
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