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Reese KL, Pantel K, Smit DJ. Multibiomarker panels in liquid biopsy for early detection of pancreatic cancer - a comprehensive review. J Exp Clin Cancer Res 2024; 43:250. [PMID: 39218911 PMCID: PMC11367781 DOI: 10.1186/s13046-024-03166-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Accepted: 08/16/2024] [Indexed: 09/04/2024] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is frequently detected in late stages, which leads to limited therapeutic options and a dismal overall survival rate. To date, no robust method for the detection of early-stage PDAC that can be used for targeted screening approaches is available. Liquid biopsy allows the minimally invasive collection of body fluids (typically peripheral blood) and the subsequent analysis of circulating tumor cells or tumor-associated molecules such as nucleic acids, proteins, or metabolites that may be useful for the early diagnosis of PDAC. Single biomarkers may lack sensitivity and/or specificity to reliably detect PDAC, while combinations of these circulating biomarkers in multimarker panels may improve the sensitivity and specificity of blood test-based diagnosis. In this narrative review, we present an overview of different liquid biopsy biomarkers for the early diagnosis of PDAC and discuss the validity of multimarker panels.
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Affiliation(s)
- Kim-Lea Reese
- Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg, 20246, Germany
| | - Klaus Pantel
- Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg, 20246, Germany.
| | - Daniel J Smit
- Institute of Tumor Biology, University Medical Center Hamburg-Eppendorf, Martinistraße 52, Hamburg, 20246, Germany.
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Dritsoula A, Camilli C, Moss SE, Greenwood J. The disruptive role of LRG1 on the vasculature and perivascular microenvironment. Front Cardiovasc Med 2024; 11:1386177. [PMID: 38745756 PMCID: PMC11091338 DOI: 10.3389/fcvm.2024.1386177] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Accepted: 04/17/2024] [Indexed: 05/16/2024] Open
Abstract
The establishment of new blood vessels, and their subsequent stabilization, is a critical process that facilitates tissue growth and organ development. Once established, vessels need to diversify to meet the specific needs of the local tissue and to maintain homeostasis. These processes are tightly regulated and fundamental to normal vessel and tissue function. The mechanisms that orchestrate angiogenesis and vessel maturation have been widely studied, with signaling crosstalk between endothelium and perivascular cells being identified as an essential component. In disease, however, new vessels develop abnormally, and existing vessels lose their specialization and function, which invariably contributes to disease progression. Despite considerable research into the vasculopathic mechanisms in disease, our knowledge remains incomplete. Accordingly, the identification of angiocrine and angiopathic molecules secreted by cells within the vascular microenvironment, and their effect on vessel behaviour, remains a major research objective. Over the last decade the secreted glycoprotein leucine-rich α-2 glycoprotein 1 (LRG1), has emerged as a significant vasculopathic molecule, stimulating defective angiogenesis, and destabilizing the existing vasculature mainly, but not uniquely, by altering both canonical and non-canonical TGF-β signaling in a highly cell and context dependent manner. Whilst LRG1 does not possess any overt homeostatic role in vessel development and maintenance, growing evidence provides a compelling case for LRG1 playing a pleiotropic role in disrupting the vasculature in many disease settings. Thus, LRG1 has now been reported to damage vessels in various disorders including cancer, diabetes, chronic kidney disease, ocular disease, and lung disease and the signaling processes that drive this dysfunction are being defined. Moreover, therapeutic targeting of LRG1 has been widely proposed to re-establish a quiescent endothelium and normalized vasculature. In this review, we consider the current status of our understanding of the role of LRG1 in vascular pathology, and its potential as a therapeutic target.
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Affiliation(s)
- Athina Dritsoula
- UCL Institute of Ophthalmology, University College London, London, United Kingdom
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Ramalhete L, Vigia E, Araújo R, Marques HP. Proteomics-Driven Biomarkers in Pancreatic Cancer. Proteomes 2023; 11:24. [PMID: 37606420 PMCID: PMC10443269 DOI: 10.3390/proteomes11030024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Revised: 07/28/2023] [Accepted: 08/03/2023] [Indexed: 08/23/2023] Open
Abstract
Pancreatic cancer is a devastating disease that has a grim prognosis, highlighting the need for improved screening, diagnosis, and treatment strategies. Currently, the sole biomarker for pancreatic ductal adenocarcinoma (PDAC) authorized by the U.S. Food and Drug Administration is CA 19-9, which proves to be the most beneficial in tracking treatment response rather than in early detection. In recent years, proteomics has emerged as a powerful tool for advancing our understanding of pancreatic cancer biology and identifying potential biomarkers and therapeutic targets. This review aims to offer a comprehensive survey of proteomics' current status in pancreatic cancer research, specifically accentuating its applications and its potential to drastically enhance screening, diagnosis, and treatment response. With respect to screening and diagnostic precision, proteomics carries the capacity to augment the sensitivity and specificity of extant screening and diagnostic methodologies. Nonetheless, more research is imperative for validating potential biomarkers and establishing standard procedures for sample preparation and data analysis. Furthermore, proteomics presents opportunities for unveiling new biomarkers and therapeutic targets, as well as fostering the development of personalized treatment strategies based on protein expression patterns associated with treatment response. In conclusion, proteomics holds great promise for advancing our understanding of pancreatic cancer biology and improving patient outcomes. It is essential to maintain momentum in investment and innovation in this arena to unearth more groundbreaking discoveries and transmute them into practical diagnostic and therapeutic strategies in the clinical context.
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Affiliation(s)
- Luís Ramalhete
- Blood and Transplantation Center of Lisbon—Instituto Português do Sangue e da Transplantação, Alameda das Linhas de Torres, n° 117, 1769-001 Lisbon, Portugal
- Nova Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal
- iNOVA4Health—Advancing Precision Medicine, RG11: Reno-Vascular Diseases Group, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal
| | - Emanuel Vigia
- Nova Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal
- Centro Hospitalar de Lisboa Central, Department of Hepatobiliopancreatic and Transplantation, 1050-099 Lisbon, Portugal
| | - Rúben Araújo
- Nova Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal
- CHRC—Comprehensive Health Research Centre, NOVA Medical School, 1150-199 Lisbon, Portugal
| | - Hugo Pinto Marques
- Nova Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, 1169-056 Lisbon, Portugal
- Centro Hospitalar de Lisboa Central, Department of Hepatobiliopancreatic and Transplantation, 1050-099 Lisbon, Portugal
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Liou GY, Byrd CJ. Diagnostic Bioliquid Markers for Pancreatic Cancer: What We Have vs. What We Need. Cancers (Basel) 2023; 15:2446. [PMID: 37173913 PMCID: PMC10177101 DOI: 10.3390/cancers15092446] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Revised: 04/14/2023] [Accepted: 04/21/2023] [Indexed: 05/15/2023] Open
Abstract
Pancreatic ductal adenocarcinoma (PDAC), the most common type of pancreatic cancer, currently has a dismal five-year survival rate of approximately 10% due to late diagnosis and a lack of efficient treatment options such as surgery. Furthermore, the majority of PDAC patients have surgically unresectable cancer, meaning cancer cells have either reached the surrounding blood vessels or metastasized to other organs distant from the pancreas area, resulting in low survival rates as compared to other types of cancers. In contrast, the five-year survival rate of surgically resectable PDAC patients is currently 44%. The late diagnosis of PDAC is a result of little or no symptoms in its early stage of development and a lack of specific biomarkers that may be utilized in routine examinations in the clinic. Although healthcare professionals understand the importance of early detection of PDAC, the research on the subject has lagged and no significant changes in the death toll of PDAC patients has been observed. This review is focused on understanding potential biomarkers that may increase the early diagnosis of PDAC patients at its surgically resectable stage. Here, we summarize the currently available biomarkers used in the clinic as well as those being developed with the hope of providing insight into the future of liquid biomarkers to be used in routine examinations for the early diagnosis of PDAC.
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Affiliation(s)
- Geou-Yarh Liou
- Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA 30314, USA
- Department of Biological Sciences, Clark Atlanta University, Atlanta, GA 30314, USA
| | - Crystal J. Byrd
- Department of Biological Sciences, Clark Atlanta University, Atlanta, GA 30314, USA
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Zou Y, Xu Y, Chen X, Wu Y, Fu L, Lv Y. Research Progress on Leucine-Rich Alpha-2 Glycoprotein 1: A Review. Front Pharmacol 2022; 12:809225. [PMID: 35095520 PMCID: PMC8797156 DOI: 10.3389/fphar.2021.809225] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Accepted: 12/13/2021] [Indexed: 12/18/2022] Open
Abstract
Leucine-rich alpha⁃2 glycoprotein 1 (LRG1) is an important member of the leucine-rich repetitive sequence protein family. LRG1 was mainly involved in normal physiological activities of the nervous system, such as synapse formation, synapse growth, the development of nerve processes, neurotransmitter transfer and release, and cell adhesion molecules or ligand-binding proteins. Also, LRG1 affected the development of respiratory diseases, hematological diseases, endocrine diseases, tumor diseases, eye diseases, cardiovascular diseases, rheumatic immune diseases, infectious diseases, etc. LRG1 was a newly discovered important upstream signaling molecule of transforming growth factor⁃β (TGF⁃β) that affected various pathological processes through the TGF⁃β signaling pathway. However, research on LRG1 and its involvement in the occurrence and development of diseases was still in its infancy and the current studies were mainly focused on proteomic detection and basic animal experimental reports. We could reasonably predict that LRG1 might act as a new direction and strategy for the treatment of many diseases.
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Affiliation(s)
- Yonghui Zou
- Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang, China.,School of Clinical Medicine, Nanchang University, Nanchang, China
| | - Yi Xu
- Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang, China.,School of Clinical Medicine, Nanchang University, Nanchang, China
| | - Xiaofeng Chen
- Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang, China.,School of Clinical Medicine, Nanchang University, Nanchang, China
| | - Yaoqi Wu
- Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang, China.,College of Pharmacy, Nanchang University, Nanchang, China
| | - Longsheng Fu
- Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yanni Lv
- Department of Pharmacy, The First Affiliated Hospital of Nanchang University, Nanchang, China
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Lin M, Liu J, Zhang F, Qi G, Tao S, Fan W, Chen M, Ding K, Zhou F. The role of leucine-rich alpha-2-glycoprotein-1 in proliferation, migration, and invasion of tumors. J Cancer Res Clin Oncol 2022; 148:283-291. [PMID: 35037101 DOI: 10.1007/s00432-021-03876-0] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 11/27/2021] [Indexed: 12/14/2022]
Abstract
BACKGROUND Leucine-rich alpha-2-glycoprotein-1 (LRG1) is widely involved in proliferation, migration, and invasion of various tumor cells. Recent studies have evaluated the potential of LRG1 as both an early tumor and a prognostic biomarker. METHOD The relevant literature from PubMed is reviewed in this article. RESULTS It has been found that LRG1 mainly acts on the regulatory mechanisms of angiogenesis, epithelial-mesenchymal transition (EMT), and apoptosis by transforming growth factor (TGF-β) signaling pathway as well as affecting the occurrence and development of the tumors. Moreover, with advancement of research, LRG1 regulation pathways which are independent of TGF-β signaling pathway have been gradually revealed in different tumor cells; There are several studies on the biological effects of LRG1 as an inflammatory factor, vascular growth regulator, cell adhesion, and a cell viability influencing factor. In addition, various tumor suppression methods which are based on regulation of LRG1 levels have also shown high potential clinical value. CONCLUSIONS LRG1 are critical for the processes of tumorigenesis, development, and metastasis in various tumors. The present study reviewed the latest research on the achievements of LRG1 in tumor genesis and development. Further, this study also discussed the related molecular mechanisms of various biological functions of LRG1.
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Affiliation(s)
- Meng Lin
- Department of Pathology, Weifang Medical University, Weifang, Shandong, People's Republic of China
| | - Jinmeng Liu
- Laboratory of Biochemistry and Molecular Biology, Weifang Medical University, Weifang, Shandong, People's Republic of China
| | - Fengping Zhang
- Department of Pathology, Weifang Medical University, Weifang, Shandong, People's Republic of China
| | - Gaoxiu Qi
- Department of Pathology, Affiliated Hospital, Weifang Medical University, Weifang, Shandong, People's Republic of China
| | - Shuqi Tao
- Department of Pathology, Weifang Medical University, Weifang, Shandong, People's Republic of China
| | - Wenyuan Fan
- Department of Pathology, Weifang Medical University, Weifang, Shandong, People's Republic of China
| | - Min Chen
- Department of Pathology, Affiliated Hospital, Weifang Medical University, Weifang, Shandong, People's Republic of China
| | - Kang Ding
- Department of Pathology, Weifang Medical University, Weifang, Shandong, People's Republic of China
| | - Fenghua Zhou
- Department of Pathology, Weifang Medical University, Weifang, Shandong, People's Republic of China.
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Yang M, Zhang CY. Diagnostic biomarkers for pancreatic cancer: An update. World J Gastroenterol 2021; 27:7862-7865. [PMID: 34963749 PMCID: PMC8661384 DOI: 10.3748/wjg.v27.i45.7862] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2021] [Revised: 08/10/2021] [Accepted: 11/24/2021] [Indexed: 02/06/2023] Open
Abstract
Pancreatic ductal adenocarcinoma accounts for the primary type of pancreatic cancer (PC) with a 5-year survival rate of only about 10% in the United States. Early diagnosis will improve chances for curative treatment. To date, a broadly used serum marker for PC diagnosis is carbohydrate antigen 19-9, which is the only approved biomarker currently by the United States Food and Drug Administration. However, it has low specificity; therefore, development of novel biomarkers is urgently needed. Clinical trials are ongoing to evaluate candidate biomarkers for PC diagnosis, and the use of a multi-biomarker panel with current PC diagnostic biomarkers appears promising.
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Affiliation(s)
- Ming Yang
- Department of Surgery, University of Missouri, Columbia, MO 65212, United States
| | - Chun-Ye Zhang
- Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65212, United States
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