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Reichmann R, Nimptsch K, Pischon T, Gunter MJ, Jenab M, Eriksen AK, Tjonneland A, Janke J, Katzke V, Kaaks R, Schulze MB, Eichelmann F, Masala G, Sieri S, Pasanisi F, Tumino R, Giraudo MT, Rothwell J, Severi G, Jakszyn P, Sanchez-Perez MJ, Amiano P, Colorado-Yohar SM, Guevara M, van Guelpen B, Aglago EK, Heath AK, Smith-Byrne K, Weiderpass E, Aleksandrova K. Sex- and site-specific associations of circulating lipocalin 2 and incident colorectal cancer: Results from the EPIC cohort. Int J Cancer 2025; 156:930-942. [PMID: 39511728 DOI: 10.1002/ijc.35205] [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: 03/23/2024] [Revised: 07/17/2024] [Accepted: 07/18/2024] [Indexed: 11/15/2024]
Abstract
Experimental research has uncovered lipocalin 2 (LCN2) as a novel biomarker implicated in the modulation of intestinal inflammation, metabolic homeostasis, and colon carcinogenesis. However, evidence from human research has been scant. We, therefore, explored the association of pre-diagnostic circulating LCN2 concentrations with incident colorectal cancer (CRC) in a nested case-control study within the in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. LCN2 was measured in 1267 incident CRC cases matched to 1267 controls using incidence density sampling. Conditional logistic regression was used to estimate incidence rate ratios (IRRs) and 95% confidence intervals (95% CIs) according to tumor subsite and sex. Weighted Cox proportional hazard regression was used to explore associations by adiposity status. In multivariable-adjusted analyses, the IRR [95% CI] per doubling in LCN2 concentration was 1.16 [0.98-1.37] for CRC overall, 1.26 [1.00-1.59] for colon cancer, and 1.08 [0.85-1.38] for rectal cancer. The association for colon cancer was more pronounced in women (IRR [95% CI], 1.66 [1.20-2.30]) and for proximal colon cancer (IRR [95% CI], 1.96 [1.15-3.34]), whereas no association was seen in men and distal colon cancer. The association for colon cancer was positive in individuals with high waist circumference (hazard ratio [95% CI], 1.69 [1.52-1.88]) and inverse in individuals with low waist circumference (hazard ratio [95% CI], 0.86 [0.76-0.98], P interaction<0.01). Overall, these data suggest that pre-diagnostic LCN2 concentrations were positively associated with colon cancer, particularly occurring in the proximal colon, in women and among individuals with abdominal adiposity.
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Grants
- Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands)
- German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany)
- Danish Cancer Society (Denmark)
- Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France)
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London
- 001 World Health Organization
- Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy)
- International Agency for Research on Cancer (IARC)
- Cancer Research UK (14,136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1,000,143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford) (United Kingdom).
- Health Research Fund (FIS)-Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology-ICO (Spain)
- Swedish Cancer Society, Swedish Research Council, Region Skåne and Region Västerbotten (Sweden)
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Affiliation(s)
- Robin Reichmann
- Biomarkers and Metabolism Research Group, Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany
| | - Katharina Nimptsch
- Molecular Epidemiology Research Group, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Biobank Technology Platform, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
| | - Tobias Pischon
- Molecular Epidemiology Research Group, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Biobank Technology Platform, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Core Facility Biobank, Berlin Institute of Health at Charité-Universitätsmedizin Berlin, Berlin, Germany
- Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Berlin, Germany
| | - Marc J Gunter
- International Agency for Research on Cancer, World Health Organization, Lyon, France
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Mazda Jenab
- International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Anne Kirstine Eriksen
- Diet, Cancer and Health Research Group, Danish Cancer Institute, Danish Cancer Society, Copenhagen, Denmark
| | - Anne Tjonneland
- Diet, Cancer and Health Research Group, Danish Cancer Institute, Danish Cancer Society, Copenhagen, Denmark
- Department of Public Health, University of Copenhagen, Copenhagen, Denmark
| | - Jürgen Janke
- Molecular Epidemiology Research Group, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
- Biobank Technology Platform, Max-Delbrueck-Center for Molecular Medicine in the Helmholtz Association (MDC), Berlin, Germany
| | - Verena Katzke
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Rudolf Kaaks
- Department of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Matthias B Schulze
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
- Institute of Nutritional Science, University of Potsdam, Nuthetal, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Fabian Eichelmann
- Department of Molecular Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
- German Center for Diabetes Research (DZD), Neuherberg, Germany
| | - Giovanna Masala
- Prevention and Clinical Network, Institute for the Study and Prevention of Cancer (ISPRO), Florenz, Italy
| | - Sabina Sieri
- Epidemiology and Prevention Unit, Fondazione IRCCS Instituto Nazionale dei Tumori, Milan, Italy
| | - Fabrizio Pasanisi
- Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
| | - Rosario Tumino
- Hyblean Association for Epidemiological Research, Associazione Iblea per la Ricerca Epidemiologica (A.I.R.E.-ONLUS), Ragusa, Italy
| | - Maria Teresa Giraudo
- Department of Clinical and Biological Sciences, University of Turin, Turin, Italy
| | - Joseph Rothwell
- CESP-Univ. Paris-Saclay, UVSQ, Inserm-"Exposome, heredity, cancer and health" Team, The Centre for Research in Epidemiology and Population Health, Villejuif, France
| | - Gianluca Severi
- CESP-Univ. Paris-Saclay, UVSQ, Inserm-"Exposome, heredity, cancer and health" Team, The Centre for Research in Epidemiology and Population Health, Villejuif, France
- Department of Statistics, Computer Science, Applications "G. Parenti" (DISIA), University of Florence, Florence, Italy
| | - Paula Jakszyn
- Unit of Nutrition and Cancer, Cancer Epidemiology Research Programme, Catalan Institute of Oncology (ICO-IDIBELL), Barcelona, Spain
- Blanquerna School of Health Sciences, Ramon Llull University, Barcelona, Spain
| | - Maria Jose Sanchez-Perez
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Public Health Research and Health Services Research Group, Andalusian School of Public Health (EASP), Granada, Andalucía, Spain
- Epidemiology, Prevention and Control of Cancer Research Group, Biosanitary Research Institute of Granada (ibs.Granada), Granada, Spain
- Department of Preventive Medicine and Public Health, University of Granada, Granada, Spain
| | - Pilar Amiano
- Sub Directorate for Public Health and Addictions of Gipuzkoa, Ministry of Health of the Basque Government, San Sebastian, Spain
- Epidemiology of Chronic and Communicable Diseases Group, Biodonostia Health Research Institute, San Sebastian, Spain
- Instituto de Salud Carlos III, CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
| | - Sandra M Colorado-Yohar
- Department of Epidemiology, Murcia Regional Health Council, Instituto Murciano de Investigación Biosanitaria, Murcia, Spain
- Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellin, Colombia
| | - Marcela Guevara
- CIBER of Epidemiology and Public Health (CIBERESP), Madrid, Spain
- Epidemiology and Health Prevention Service, Institute of Public Health and Labor of Navarre, Pamplona, Navarra, Spain
- Epidemiology of Cancer and Other Chronic Diseases Research Group, Healthcare Research Institute of Navarre (IdiSNA), Pamplona, Spain
| | - Bethany van Guelpen
- Department of Radiation Sciences, Umeå University, Umeå, Sweden
- Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
| | - Elom K Aglago
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Alicia K Heath
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK
| | - Karl Smith-Byrne
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
| | - Elisabete Weiderpass
- International Agency for Research on Cancer, World Health Organization, Lyon, France
| | - Krasimira Aleksandrova
- Biomarkers and Metabolism Research Group, Department of Epidemiological Methods and Etiological Research, Leibniz Institute for Prevention Research and Epidemiology, Bremen, Germany
- Faculty of Human and Health Sciences, University of Bremen, Bremen, Germany
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Rixon A, Meyer E, Daminet S, Goddard A, Kongtasai T, Pazzi P. Influence of Carcinoma and Sarcoma on Neutrophil Gelatinase-Associated Lipocalin and Symmetric Dimethylarginine Concentrations in Dogs. J Vet Intern Med 2025; 39:e70015. [PMID: 40042235 PMCID: PMC11881161 DOI: 10.1111/jvim.70015] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2024] [Revised: 01/09/2025] [Accepted: 01/09/2025] [Indexed: 05/12/2025] Open
Abstract
BACKGROUND It is unknown if tumors or concomitant renal disease influence neutrophil gelatinase-associated lipocalin (NGAL) and symmetric dimethylarginine (SDMA) concentrations in tumor-bearing dogs. OBJECTIVES Determine the effect of tumor presence, tumor type, and metastasis on concentrations of serum NGAL (sNGAL), SDMA, urinary NGAL (uNGAL), and uNGAL-to-creatinine ratio (uNGAL/Cr) in dogs with carcinoma or sarcoma without clinically relevant renal disease. ANIMALS Twenty-one dogs with carcinoma, 18 with sarcoma, and 20 healthy age-controlled dogs. METHODS Concentrations of sNGAL, SDMA, and uNGAL, and uNGAL/Cr ratio were measured from banked samples collected during a previous prospective study. Patient clinicopathological and histopathology records were reviewed, and those with renal azotemia or moderate to severe histopathological renal abnormalities were classified as having clinically relevant renal disease. Biomarker concentrations were compared between tumor-bearing dogs without clinically relevant renal disease and healthy age-controlled dogs. Additionally, comparisons were made between dogs with carcinoma and sarcoma, as well as between dogs with and without metastasis. Correlations between uNGAL and sNGAL concentrations, along with acute phase protein (APP) concentrations, were also analyzed. RESULTS Tumor-bearing dogs without clinically relevant renal disease had increased uNGAL/Cr (p < 0.001), but not sNGAL, compared with healthy controls. Although median SDMA concentrations did not significantly differ between groups, increased concentrations were found in 32% of dogs with carcinoma and 20% of dogs with sarcoma. No differences were found between dogs with carcinoma and those with sarcoma, or between dogs with metastasis and those without. Urinary and serum NGAL concentrations were moderately correlated, while weak to no correlations were observed with APPs. CONCLUSION Carcinomas and sarcomas, but not metastasis, influence uNGAL/Cr and SDMA concentrations in dogs.
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Affiliation(s)
- Anouska Rixon
- Department of Companion Animal Clinical StudiesFaculty of Veterinary Science, University of PretoriaPretoriaSouth Africa
| | - Evelyne Meyer
- Department of Veterinary and BiosciencesFaculty of Veterinary Medicine, Ghent UniversityMerelbekeBelgium
| | - Sylvie Daminet
- Department of Small AnimalsFaculty of Veterinary Medicine, Ghent UniversityMerelbekeBelgium
| | - Amelia Goddard
- Department of Companion Animal Clinical StudiesFaculty of Veterinary Science, University of PretoriaPretoriaSouth Africa
| | - Thirawut Kongtasai
- Department of Small AnimalsFaculty of Veterinary Medicine, Ghent UniversityMerelbekeBelgium
- Department of Clinical Sciences and Public HealthFaculty of Veterinary Science, Mahidol UniversityNakhon PathomThailand
| | - Paolo Pazzi
- Department of Companion Animal Clinical StudiesFaculty of Veterinary Science, University of PretoriaPretoriaSouth Africa
- Department of Small Animal Clinical SciencesCollege of Veterinary Medicine, University of TennesseeKnoxvilleTennesseeUSA
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Zhang ZX, Peng J, Ding WW. Lipocalin-2 and intestinal diseases. World J Gastroenterol 2024; 30:4864-4879. [PMID: 39679305 PMCID: PMC11612708 DOI: 10.3748/wjg.v30.i46.4864] [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: 04/27/2024] [Revised: 09/25/2024] [Accepted: 11/04/2024] [Indexed: 11/21/2024] Open
Abstract
Dysfunction of the intestinal barrier is a prevalent phenomenon observed across a spectrum of diseases, encompassing conditions such as mesenteric artery dissection, inflammatory bowel disease, cirrhosis, and sepsis. In these pathological states, the integrity of the intestinal barrier, which normally serves to regulate the selective passage of substances between the gut lumen and the bloodstream, becomes compromised. This compromised barrier function can lead to a range of adverse consequences, including increased permeability to harmful substances, the translocation of bacteria and their products into systemic circulation, and heightened inflammatory responses within the gut and beyond. Understanding the mechanisms underlying intestinal barrier dysfunction in these diverse disease contexts is crucial for the development of targeted therapeutic interventions aimed at restoring barrier integrity and ameliorating disease progression. Lipocalin-2 (LCN2) expression is significantly upregulated during episodes of intestinal inflammation, making it a pivotal indicator for gauging the extent of such inflammatory processes. Notably, however, LCN2 derived from distinct cellular sources, whether intestinal epithelial cells or immune cells, exhibits notably divergent functional characteristics. Furthermore, the multifaceted nature of LCN2 is underscored by its varying roles across different diseases, sometimes even demonstrating contradictory effects.
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Affiliation(s)
- Zhong-Xu Zhang
- Department of Trauma and Acute Care Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, Jiangsu Province, China
| | - Jian Peng
- Department of Trauma and Acute Care Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, Jiangsu Province, China
| | - Wei-Wei Ding
- Department of Trauma and Acute Care Surgery, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210002, Jiangsu Province, China
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Lumlertgul N, Ostermann M, McCorkell S, van Dellen J, Williams AB. Association of plasma and urine NGAL with acute kidney injury after elective colorectal surgery: A cohort study. Ann Med Surg (Lond) 2021; 62:315-322. [PMID: 33552490 PMCID: PMC7847815 DOI: 10.1016/j.amsu.2021.01.060] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Revised: 01/16/2021] [Accepted: 01/17/2021] [Indexed: 11/13/2022] Open
Abstract
Background Acute kidney injury (AKI) is common in surgical patients. We aimed to investigate the validity of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) in the detection of AKI and prediction of outcomes in patients undergoing major colorectal surgery. Materials and methods This was a pre-specified post-hoc analysis of a randomized controlled trial comparing oesophageal doppler and Lithium dilution cardiac output monitoring in high risk patients undergoing major colorectal surgery as part of an Enhanced Recovery After Surgery protocol in a tertiary care hospital. Plasma and urine samples for NGAL measurement were taken before surgery (T1), immediately after surgery (T2), and on postoperative day 1 (T3). AKI was defined according to the KDIGO criteria. Results A total of 89 patients were included of whom 12 (13.5%) developed AKI. Plasma NGAL significantly increased from T1 to T3 in both AKI (p < 0.001) and non-AKI (p = 0.048) patients, while urine NGAL did not change over time. There were no significant differences in plasma and urine NGAL in patients with and without AKI at all time points. Postoperative day 1 urine NGAL concentrations were significantly higher in non-survivors than survivors (41.2 versus 25 ng/mL, p = 0.026). One-year mortality was significantly higher in AKI patients with a raised urine NGAL compared to AKI patients without elevated urine NGAL levels. Conclusions Plasma and urine NGAL poorly predicted AKI post-colorectal surgery. Non-survivors had higher urine NGAL results. More research is required to explore the association between NGAL and long-term outcomes.
Acute kidney injury occurred in 13.5% of patients undergoing major elective colorectal surgery. Plasma and urine NGAL poorly predicted AKI after major elective colorectal surgery. The association of NGAL and AKI appears to be confounded by malignancy and chronic kidney disease. 1-year mortality in AKI patients with a raised urine NGAL was higher than in patients with AKI and a normal urine NGAL value.
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Affiliation(s)
- Nuttha Lumlertgul
- Department of Critical Care, Guy's & St Thomas' Hospital, London, UK.,Division of Nephrology, Department of Internal Medicine, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.,Excellence Center for Critical Care Nephrology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand.,Research Unit in Critical Care Nephrology, Chulalongkorn University, Bangkok, Thailand
| | - Marlies Ostermann
- Department of Critical Care, Guy's & St Thomas' Hospital, London, UK
| | - Stuart McCorkell
- Department of Anaesthesia, Guy's & St Thomas' Hospital, London, UK
| | | | - Andrew B Williams
- Department of Colorectal Surgery, Guy's & St Thomas' Hospital, London, UK
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Basu S, Chaudhary N, Shah S, Braggs C, Sawant A, Vaz S, Thorat R, Gupta S, Dalal SN. Plakophilin3 loss leads to an increase in lipocalin2 expression, which is required for tumour formation. Exp Cell Res 2018; 369:251-265. [PMID: 29803740 DOI: 10.1016/j.yexcr.2018.05.026] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2017] [Revised: 05/22/2018] [Accepted: 05/23/2018] [Indexed: 12/17/2022]
Abstract
An increase in tumour formation and metastasis are observed upon plakophilin3 (PKP3) loss. To identify pathways downstream of PKP3 loss that are required for increased tumour formation, a gene expression analysis was performed, which demonstrated that the expression of lipocalin2 (LCN2) was elevated upon PKP3 loss and this is consistent with expression data from human tumour samples suggesting that PKP3 loss correlates with an increase in LCN2 expression. PKP3 loss leads to an increase in invasion, tumour formation and metastasis and these phenotypes were dependent on the increase in LCN2 expression. The increased LCN2 expression was due to an increase in the activation of p38 MAPK in the HCT116 derived PKP3 knockdown clones as LCN2 expression decreased upon inhibition of p38 MAPK. The phosphorylated active form of p38 MAPK is translocated to the nucleus upon PKP3 loss and is dependent on complex formation between p38 MAPK and PKP3. WT PKP3 inhibits LCN2 reporter activity in PKP3 knockdown cells but a PKP3 mutant that fails to form a complex with p38 MAPK cannot suppress LCN2 promoter activity. Further, LCN2 expression is decreased upon loss of p38β, but not p38α, in the PKP3 knockdown cells. These results suggest that PKP3 loss leads to an increase in the nuclear translocation of p38 MAPK and p38β MAPK is required for the increase in LCN2 expression.
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Affiliation(s)
- Srikanta Basu
- Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar Node, Navi Mumbai, Maharashtra, India; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400085, India
| | - Nazia Chaudhary
- Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar Node, Navi Mumbai, Maharashtra, India; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400085, India
| | - Sanket Shah
- Epigenetics and Chromatin Biology Group, Gupta Lab, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400085, India
| | - Carol Braggs
- Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar Node, Navi Mumbai, Maharashtra, India
| | - Aakanksha Sawant
- Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar Node, Navi Mumbai, Maharashtra, India
| | - Simone Vaz
- Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar Node, Navi Mumbai, Maharashtra, India
| | - Rahul Thorat
- Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar Node, Navi Mumbai, Maharashtra, India
| | - Sanjay Gupta
- Epigenetics and Chromatin Biology Group, Gupta Lab, Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, India; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400085, India
| | - Sorab N Dalal
- Advanced Centre for Treatment Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar Node, Navi Mumbai, Maharashtra, India; Homi Bhabha National Institute, Training School Complex, Anushakti Nagar, Mumbai 400085, India.
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Kim SL, Lee ST, Min IS, Park YR, Lee JH, Kim DG, Kim SW. Lipocalin 2 negatively regulates cell proliferation and epithelial to mesenchymal transition through changing metabolic gene expression in colorectal cancer. Cancer Sci 2017; 108:2176-2186. [PMID: 28859238 PMCID: PMC5666039 DOI: 10.1111/cas.13389] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2017] [Revised: 08/20/2017] [Accepted: 08/25/2017] [Indexed: 12/17/2022] Open
Abstract
Lipocalin 2 (LCN2), a member of the lipocalin superfamily, plays an important role in oncogenesis and progression in various types of cancer. However, the expression pattern and functional role of LCN2 in colorectal cancer (CRC) is still poorly understood. The purpose of the present study was to investigate whether LCN2 is associated with proliferation and the epithelial-mesenchymal transition (EMT) in CRC and to elucidate the underlying signaling pathways. LCN2 was preferentially expressed in CRC cells compared to normal tissues. However, LCN2 expression was significantly lower in metastatic or advanced-stage CRC than in non-metastatic or early stage CRC. Knockdown of LCN2 using small interfering RNA (siRNA) in CRC cells expressing a high level of LCN2 induced cell proliferation and a morphological switch from an epithelial to mesenchymal state. Furthermore, downregulation of LCN2 in CRC cells increased cell migration and invasion involved in the regulation of EMT markers. Knockdown of LCN2 also induced glucose consumption and lactate production, accompanied by an increase in energy metabolism-related genes. Taken together, our findings indicated that LCN2 negatively modulated proliferation, EMT and energy metabolism in CRC cells. Accordingly, LCN2 may be a candidate metastasis suppressor and potential therapeutic target in CRC.
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Affiliation(s)
- Se-Lim Kim
- Department of Internal Medicine Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.,Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea
| | - Soo Teik Lee
- Department of Internal Medicine Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.,Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea
| | - In Suk Min
- Department of Internal Medicine Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.,Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea
| | - Young Ran Park
- Department of Internal Medicine Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.,Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea
| | - Ju Hyung Lee
- Department of Preventive Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea
| | - Dae-Ghon Kim
- Department of Internal Medicine Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.,Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea
| | - Sang-Wook Kim
- Department of Internal Medicine Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea.,Biomedical Research Institute, Chonbuk National University Hospital, Chonbuk National University Medical School, Jeonju, Korea
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7
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Can NGAL be employed as prognostic and diagnostic biomarker in human cancers? A systematic review of current evidence. Int J Biol Markers 2017; 32:e53-e61. [PMID: 28106227 DOI: 10.5301/jbm.5000245] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/17/2016] [Indexed: 12/30/2022]
Abstract
BACKGROUND Some studies have reported differentially altered neutrophil gelatinase-associated lipocalin (NGAL) levels in several malignancies. We evaluated NGAL measured in plasma or urine as both prognostic and diagnostic marker for different types of human tumors. METHODS We performed systematic electronic searches in Medline, Embase and CRDTAS. Studies were included if they evaluated NGAL as a prognostic or diagnostic marker for human cancers. The selection of the studies, screening of the full texts and data extraction were conducted independently by 2 authors. We used the random-effects model for the meta-analyses. A methodological assessment was completed. RESULTS We included 35 studies dedicated to colorectal, pancreas, breast, thyroid, gastric, kidney, endometrial, brain, liver, lung, esophageal, oral and ovarian cancers. Our meta-analyses showed that, in patients with colorectal and breast cancer, positive NGAL expression was associated with a decrease of disease-free survival (hazard ratio [HR] = 2.27, 95% confidence interval [95% CI], 1.54-3.36; HR = 1.78, 95% CI, 1.33-2.38, respectively). NGAL was a negative prognostic marker of overall survival in colorectal (HR = 2.37, 95% CI, 1.68-3.34) and endometrial (HR = 4.38, 95% CI, 1.9-10.12) cancers. Discriminative power of NGAL between cancer patients and control was moderate in colorectal cancer (area under the curve [AUC] = 0.6; pooled sensitivity 0.56; pooled specificity 0.72), acceptable in pancreatic cancer (AUC = 0.8; pooled sensitivity 0.6; pooled specificity 0.8) and good in thyroid cancer (AUC = 0.9; pooled sensitivity 0.85; pooled specificity 0.96). CONCLUSIONS NGAL determination in plasma and urine could be useful in the prognosis of colorectal and breast cancer, but its prognostic accuracy remains uncertain for other human tumors.
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Muşlu N, Ercan B, Akbayır S, Balcı Ş, Ovla HD, Bozlu M. Neutrophil gelatinase-associated lipocalin as a screening test in prostate cancer. Turk J Urol 2017; 43:30-35. [PMID: 28270948 PMCID: PMC5330265 DOI: 10.5152/tud.2016.08941] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2016] [Accepted: 11/01/2016] [Indexed: 12/25/2022]
Abstract
OBJECTIVE Prostate specific antigen (PSA) with digital rectal examination is used for diagnosis of prostate cancer (PCa), where definite diagnosis can only be made by prostate biopsy. Recently neutrophil gelatinase-associated lipocalin (NGAL), a lipocalin family member glycoprotein, come into prominence as a cancer biomarker. This study is aimed to test serum NGAL as a diagnostic biomarker for PCa and discriminate PCa from benign prostatic hyperplasia (BPH). MATERIAL AND METHODS In this prospective study, 90 patients who underwent transrectal ultrasound-guided 12-core prostate biopsy between May 2015 and September 2015, were evaluated. Histopathologically diagnosed 45 PCa and 45 BPH patients were enrolled in this study. Serum NGAL and PSA levels of all participants were measured, then these data were evaluated by statistical programs. RESULTS When sensitivity fixed to 80% specificity of NGAL was better than PSA (49%, 31% respectively). Receiver operating characteristic (ROC) curve analysis showed that NGAL alone or its combined use with PSA have better area under curve (AUC) results than PSA alone (0.662, 0.693, and 0.623 respectively). CONCLUSION In conclusion NGAL gave promising results such as increased sensitivity and a better AUC values in order to distinguish PCa from BPH. NGAL showed a potential to be a non-invasive biomarker which may decrease the number of unnecessary biopsies.
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Affiliation(s)
- Necati Muşlu
- Department of Biochemistry, Mersin University School of Medicine, Mersin, Turkey
| | - Bahadır Ercan
- Department of Biochemistry, Dicle University School of Medicine, Diyarbakır, Turkey
| | - Serin Akbayır
- Karaman State Hospital, Biochemistry Laboratory, Karaman, Turkey
| | - Şenay Balcı
- Department of Biochemistry, Mersin University School of Medicine, Mersin, Turkey
| | - H. Didem Ovla
- Department of Biostatistics Mersin University School of Medicine, Mersin, Turkey
| | - Murat Bozlu
- Department of Urology, Mersin University School of Medicine, Mersin, Turkey
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9
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Uzozie AC, Selevsek N, Wahlander A, Nanni P, Grossmann J, Weber A, Buffoli F, Marra G. Targeted Proteomics for Multiplexed Verification of Markers of Colorectal Tumorigenesis. Mol Cell Proteomics 2017; 16:407-427. [PMID: 28062797 DOI: 10.1074/mcp.m116.062273] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2016] [Revised: 01/04/2017] [Indexed: 12/11/2022] Open
Abstract
Targeted proteomic methods can accelerate the verification of multiple tumor marker candidates in large series of patient samples. We utilized the targeted approach known as selected/multiple reaction monitoring (S/MRM) to verify potential protein markers of colorectal adenoma identified by our group in previous transcriptomic and quantitative shotgun proteomic studies of a large cohort of precancerous colorectal lesions. We developed SRM assays to reproducibly detect and quantify 25 (62.5%) of the 40 selected proteins in an independent series of precancerous and cancerous tissue samples (19 adenoma/normal mucosa pairs; 17 adenocarcinoma/normal mucosa pairs). Twenty-three proteins were significantly up-regulated (n = 17) or downregulated (n = 6) in adenomas and/or adenocarcinomas, as compared with normal mucosa (linear fold changes ≥ ±1.3, adjusted p value <0.05). Most changes were observed in both tumor types (up-regulation of ANP32A, ANXA3, SORD, LDHA, LCN2, NCL, S100A11, SERPINB5, CDV3, OLFM4, and REG4; downregulation of ARF6 and PGM5), and a five-protein biomarker signature distinguished neoplastic tissue from normal mucosa with a maximum area under the receiver operating curve greater than 0.83. Other changes were specific for adenomas (PPA1 and PPA2 up-regulation; KCTD12 downregulation) or adenocarcinoma (ANP32B, G6PD, RCN1, and SET up-regulation; downregulated AKR1B1, APEX1, and PPA1). Some changes significantly correlated with a few patient- or tumor-related phenotypes. Twenty-two (96%) of the 23 proteins have a potential to be released from the tumors into the bloodstream, and their detectability in plasma has been previously reported. The proteins identified in this study expand the pool of biomarker candidates that can be used to develop a standardized precolonoscopy blood test for the early detection of colorectal tumors.
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Affiliation(s)
| | - Nathalie Selevsek
- §Functional Genomics Center Zurich, University/ETH Zurich, Zurich, Switzerland
| | - Asa Wahlander
- §Functional Genomics Center Zurich, University/ETH Zurich, Zurich, Switzerland
| | - Paolo Nanni
- §Functional Genomics Center Zurich, University/ETH Zurich, Zurich, Switzerland
| | - Jonas Grossmann
- §Functional Genomics Center Zurich, University/ETH Zurich, Zurich, Switzerland
| | - Achim Weber
- ¶Institute of Surgical Pathology, University of Zurich, Switzerland
| | - Federico Buffoli
- ‖ Gastroenterology and Endoscopy Unit, Hospital of Cremona, Italy
| | - Giancarlo Marra
- From the ‡Institute of Molecular Cancer Research, University of Zurich, Switzerland;
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10
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Bchir S, Nasr HB, Bouchet S, Benzarti M, Garrouch A, Tabka Z, Susin S, Chahed K, Bauvois B. Concomitant elevations of MMP-9, NGAL, proMMP-9/NGAL and neutrophil elastase in serum of smokers with chronic obstructive pulmonary disease. J Cell Mol Med 2016; 21:1280-1291. [PMID: 28004483 PMCID: PMC5487915 DOI: 10.1111/jcmm.13057] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2016] [Accepted: 11/10/2016] [Indexed: 12/22/2022] Open
Abstract
A growing body of evidence points towards smoking‐related phenotypic differences in chronic obstructive pulmonary disease (COPD). As COPD is associated with systemic inflammation, we determined whether smoking status is related to serum levels of matrix metalloproteinase‐9 (pro‐ and active MMP‐9), neutrophil gelatinase‐associated lipocalin (NGAL) and the proMMP‐9/NGAL complex in patients with COPD. Serum samples were collected in 100 stable‐phase COPD patients (82 smokers, 18 never‐smokers) and 28 healthy adults (21 smokers, 7 never‐smokers). Serum levels of studied factors were measured in ELISA. Our data provide the first evidence of simultaneously elevated serum levels of MMP‐9, NGAL and proMMP‐9/NGAL in COPD smokers. While the triad discriminated between smokers and non‐smokers in the COPD group, MMP‐9 and proMMP‐9/NGAL (but not NGAL) discriminated between smokers with and without COPD. Adjustment for age and smoking pack‐years did not alter the findings. Serum MMP‐9, NGAL and proMMP‐9/NGAL levels were not correlated with the GOLD stage or FEV1 decline. Furthermore, serum levels of neutrophil elastase (NE) and MMP‐3 (but not of IL‐6 and MMP‐12) were also higher in COPD smokers than in healthy smokers before and after adjustment for age and pack‐years. Among COPD smokers, levels of MMP‐9, NGAL and proMMP‐9/NGAL were positively correlated with NE (P < 0.0001) but not with the remaining factors. Gelatin zymography detected proMMP‐9 in serum samples of healthy and COPD smoking groups. Our results suggest that associated serum levels of proMMP‐9, NGAL, proMMP‐9/NGAL and NE may reflect the state of systemic inflammation in COPD related to cigarette smoking.
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Affiliation(s)
- Sarra Bchir
- Unité de recherche UR12ES06, Physiologie de l'Exercice et Physiopathologie de l'Intégré au Moléculaire, Biologie, Médecine et Santé, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia.,Institut Supérieur de Biotechnologie de Monastir, Université de Monastir, Monastir, Tunisia.,Centre de Recherche des Cordeliers, INSERM UMRS1138, Sorbonne Universités UPMC Paris 06, Université Paris Descartes Sorbonne Paris Cité, Paris, France
| | - Hela Ben Nasr
- Unité de recherche UR12ES06, Physiologie de l'Exercice et Physiopathologie de l'Intégré au Moléculaire, Biologie, Médecine et Santé, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia
| | - Sandrine Bouchet
- Centre de Recherche des Cordeliers, INSERM UMRS1138, Sorbonne Universités UPMC Paris 06, Université Paris Descartes Sorbonne Paris Cité, Paris, France.,Assistance Publique des Hôpitaux de Paris, Paris, France
| | - Mohamed Benzarti
- Service de Pneumo-Allergologie, CHU Farhat Hached, Sousse, Tunisia
| | | | - Zouhair Tabka
- Unité de recherche UR12ES06, Physiologie de l'Exercice et Physiopathologie de l'Intégré au Moléculaire, Biologie, Médecine et Santé, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia
| | - Santos Susin
- Centre de Recherche des Cordeliers, INSERM UMRS1138, Sorbonne Universités UPMC Paris 06, Université Paris Descartes Sorbonne Paris Cité, Paris, France
| | - Karim Chahed
- Unité de recherche UR12ES06, Physiologie de l'Exercice et Physiopathologie de l'Intégré au Moléculaire, Biologie, Médecine et Santé, Faculté de Médecine de Sousse, Université de Sousse, Sousse, Tunisia.,Faculté des Sciences de Sfax, Université de Sfax, Sfax, Tunisia
| | - Brigitte Bauvois
- Centre de Recherche des Cordeliers, INSERM UMRS1138, Sorbonne Universités UPMC Paris 06, Université Paris Descartes Sorbonne Paris Cité, Paris, France
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11
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Marfà S, Marti J, Reyes A, Casals G, Fernández-Varo G, Carvajal S, García-Valdecasas JC, Fuster J, Jiménez W. Metastatic Tissue Proteomic Profiling Predicts 5-Year Outcomes in Patients with Colorectal Liver Metastases. Transl Oncol 2016; 9:445-452. [PMID: 27751349 PMCID: PMC5067925 DOI: 10.1016/j.tranon.2016.08.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 08/03/2016] [Accepted: 08/08/2016] [Indexed: 01/05/2023] Open
Abstract
Colorectal cancer (CRC) is one of the most common cancers in the developed countries, and nearly 70% of patients with CRC develop colorectal liver metastases (CRLMs). During the last decades, several scores have been proposed to predict recurrence after CRLM resection. However, these risk scoring systems do not accurately reflect the prognosis of these patients. Therefore, this investigation was designed to identify a proteomic profile in human hepatic tumor samples to classify patients with CRLM as “mild” or “severe” based on the 5-year survival. The study was performed on 85 CRLM tumor samples. Firstly, to evaluate any distinct tumor proteomic signatures between mild and severe CRLM patients, a training group of 57 CRLM tumor samples was characterized by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry, and a classification and regression tree (CART) analysis was subsequently performed. Finally, 28 CRLM tumor samples were used to confirm and validate the results obtained. Based on all the protein peaks detected in the training group, the CART analysis was generated, and four peaks were considered to be the most relevant to construct a diagnostic algorithm. Indeed, the multivariate model yielded a sensitivity of 85.7% and a specificity of 86.1%, respectively. In addition, the receiver operating characteristic (ROC) curve showed an excellent diagnostic accuracy to discriminate mild from severe CRLM patients (area under the ROC: 0.903). Finally, the validation process yielded a sensitivity and specificity of 68.8% and 83.3%, respectively. We identified a proteomic profile potentially useful to determine the prognosis of CRLM patients based on the 5-year survival.
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Affiliation(s)
- Santiago Marfà
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Josep Marti
- HepatoBilioPancreatic Surgery and Transplant Unit Department of Surgery, ICMDM, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Adalgiza Reyes
- HepatoBilioPancreatic Surgery and Transplant Unit Department of Surgery, ICMDM, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Gregori Casals
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - Guillermo Fernández-Varo
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biomedicine, University of Barcelona, Barcelona, Spain
| | - Silvia Carvajal
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
| | - J C García-Valdecasas
- HepatoBilioPancreatic Surgery and Transplant Unit Department of Surgery, ICMDM, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Josep Fuster
- HepatoBilioPancreatic Surgery and Transplant Unit Department of Surgery, ICMDM, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
| | - Wladimiro Jiménez
- Biochemistry and Molecular Genetics Service, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain; Department of Biomedicine, University of Barcelona, Barcelona, Spain.
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12
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Kalanxhi E, Hektoen HH, Meltzer S, Dueland S, Flatmark K, Ree AH. Circulating proteins in response to combined-modality therapy in rectal cancer identified by antibody array screening. BMC Cancer 2016; 16:536. [PMID: 27461255 PMCID: PMC4962367 DOI: 10.1186/s12885-016-2601-x] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/24/2016] [Accepted: 07/22/2016] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND The increasingly complex programs of contemporary cancer therapy emphasize the need for biological indicators of both therapeutic response and adverse effects. One example is combined-modality treatment aimed at improving long-term outcome in patients with locally advanced rectal cancer, which commonly comes at the price of extended limits of patient tolerance. METHODS In a prospective study with intensified neoadjuvant treatment of rectal cancer patients, using an antibody array, the profiling of approximately 500 proteins was performed in serial serum samples collected at different stages of the treatment course. RESULTS The small number of proteins whose levels significantly changed after induction neoadjuvant chemotherapy (NACT) expanded substantially following the sequential chemoradiotherapy (CRT) and persisted four weeks later at treatment evaluation before pelvic surgery. Serum levels of proteins selected for validation of the experimental design, lipocalin-2 and matrix metalloproteinase-9, declined after NACT and gradually reverted to baseline values during the remaining neoadjuvant course. Of note, the greater the decline in post-NACT and post-CRT matrix metalloproteinase-9 levels, the more favorable progression-free survival. No correlation was found, however, with diarrhea scores, the clinical correlate of adverse therapeutic effects. CONCLUSIONS Even though the findings were indicative of only tumor and not normal tissue effects, multiplex immunoassay analysis of circulating proteins in patients undergoing combined-modality therapy may in principle dissect the contribution of the individual modalities to overall systemic responses in patient outcome and tolerance. TRIAL REGISTRATION ClinicalTrials.gov NCT00278694 ; registration date: January 16, 2006, retrospective to enrollment of the first 10 patients of the current report.
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Affiliation(s)
- Erta Kalanxhi
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway.,Institute of Clinical Molecular Biology, Akershus University Hospital, P.O. Box 1000, 1478, Lørenskog, Norway
| | - Helga Helseth Hektoen
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway.,Institute of Clinical Medicine, University of Oslo, P.O. Box 1171, Blindern, 0318, Oslo, Norway.,Department of Tumor Biology, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway
| | - Sebastian Meltzer
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway.,Institute of Clinical Medicine, University of Oslo, P.O. Box 1171, Blindern, 0318, Oslo, Norway
| | - Svein Dueland
- Department of Oncology, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway
| | - Kjersti Flatmark
- Institute of Clinical Medicine, University of Oslo, P.O. Box 1171, Blindern, 0318, Oslo, Norway.,Department of Tumor Biology, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway.,Department of Gastroenterological Surgery, Oslo University Hospital - Norwegian Radium Hospital, P.O. Box 4950, Nydalen, 0424, Oslo, Norway
| | - Anne Hansen Ree
- Department of Oncology, Akershus University Hospital, Lørenskog, Norway. .,Institute of Clinical Medicine, University of Oslo, P.O. Box 1171, Blindern, 0318, Oslo, Norway.
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13
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Cristóbal I, Torrejón B, González-Alonso P, Manso R, Rojo F, García-Foncillas J. Downregulation of miR-138 as a Contributing Mechanism to Lcn-2 Overexpression in Colorectal Cancer with Liver Metastasis. World J Surg 2016; 40:1021-2. [PMID: 26316117 DOI: 10.1007/s00268-015-3241-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Affiliation(s)
- Ion Cristóbal
- Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz-UAM, University Hospital "Fundacion Jimenez Diaz", Avda. Reyes Católicos-2, 28040, Madrid, Spain.
| | - Blanca Torrejón
- Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz-UAM, University Hospital "Fundacion Jimenez Diaz", Avda. Reyes Católicos-2, 28040, Madrid, Spain
| | - Paula González-Alonso
- Pathology Department, IIS-Fundacion Jimenez Diaz-UAM, University Hospital "Fundacion Jimenez Diaz", 28040, Madrid, Spain
| | - Rebeca Manso
- Pathology Department, IIS-Fundacion Jimenez Diaz-UAM, University Hospital "Fundacion Jimenez Diaz", 28040, Madrid, Spain
| | - Federico Rojo
- Pathology Department, IIS-Fundacion Jimenez Diaz-UAM, University Hospital "Fundacion Jimenez Diaz", 28040, Madrid, Spain
| | - Jesús García-Foncillas
- Translational Oncology Division, Oncohealth Institute, IIS-Fundacion Jimenez Diaz-UAM, University Hospital "Fundacion Jimenez Diaz", Avda. Reyes Católicos-2, 28040, Madrid, Spain.
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14
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Cobrin AR, Blois SL, Abrams-Ogg ACG, Kruth SA, Dewey C, Holowaychuk MK, Gauthier V. Neutrophil gelatinase-associated lipocalin in dogs with chronic kidney disease, carcinoma, lymphoma and endotoxaemia. J Small Anim Pract 2016; 57:291-8. [DOI: 10.1111/jsap.12481] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/20/2014] [Revised: 11/16/2015] [Accepted: 01/15/2016] [Indexed: 01/03/2023]
Affiliation(s)
- A. R. Cobrin
- Department of Clinical Studies, Ontario Veterinary College; University of Guelph; Guelph Ontario Canada N1G 2W1
| | - S. L. Blois
- Department of Clinical Studies, Ontario Veterinary College; University of Guelph; Guelph Ontario Canada N1G 2W1
| | - A. C. G. Abrams-Ogg
- Department of Clinical Studies, Ontario Veterinary College; University of Guelph; Guelph Ontario Canada N1G 2W1
| | - S. A. Kruth
- Department of Clinical Studies, Ontario Veterinary College; University of Guelph; Guelph Ontario Canada N1G 2W1
| | - C. Dewey
- Department of Population Medicine, Ontario Veterinary College; University of Guelph; Guelph Ontario Canada N1G 2W1
| | - M. K. Holowaychuk
- Department of Clinical Studies, Ontario Veterinary College; University of Guelph; Guelph Ontario Canada N1G 2W1
| | - V. Gauthier
- Department of Clinical Studies, Ontario Veterinary College; University of Guelph; Guelph Ontario Canada N1G 2W1
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15
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Du ZP, Wu BL, Xie YM, Zhang YL, Liao LD, Zhou F, Xie JJ, Zeng FM, Xu XE, Fang WK, Li EM, Xu LY. Lipocalin 2 promotes the migration and invasion of esophageal squamous cell carcinoma cells through a novel positive feedback loop. BIOCHIMICA ET BIOPHYSICA ACTA 2015; 1853:2240-50. [PMID: 26190820 DOI: 10.1016/j.bbamcr.2015.07.007] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Revised: 06/30/2015] [Accepted: 07/15/2015] [Indexed: 02/05/2023]
Abstract
Lipocalin 2 (LCN2) is a poor prognostic factor in esophageal squamous cell carcinoma (ESCC), however its functional roles and molecular mechanisms of action remain to be clarified. Here, we described the functions and signaling pathways for LCN2 in ESCC. Overexpression of LCN2 in ESCC cells accelerated cell migration and invasion in vitro, and promoted lung metastasis in vivo. Blocking LCN2 expression inhibited its pro-oncogenic effect. Either overexpression of LCN2 or treatment with recombinant human LCN2 protein enhanced the activation of MEK/ERK pathway, which in turn increases endogenous LCN2 to increase MMP-9 activity. The decreased p-cofilin and increased p-ERM induced by pERK1/2 cause the cytoskeleton F-actin rearrangement and alter the behavior of ESCC cells mediated by LCN2. As a consequence, activation of MMP-9 and the rearrangement of F-actin throw light on the mechanisms for LCN2 in ESCC. These results imply that LCN2 promotes the migration and invasion of ESCC cells through a novel positive feedback loop.
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Affiliation(s)
- Ze-Peng Du
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, China; Department of Pathology, Shantou Central Hospital, Affiliated Shantou Hospital of Sun Yat-sen University, Shantou 515041, Guangdong Province 515041, China
| | - Bing-Li Wu
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China
| | - Yang-Min Xie
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Department of Experimental Animal Center, Shantou University Medical College, Shantou 515041, China
| | - Ying-Li Zhang
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China
| | - Lian-Di Liao
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, China
| | - Fei Zhou
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Department of Experimental Animal Center, Shantou University Medical College, Shantou 515041, China
| | - Jian-Jun Xie
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China
| | - Fa-Min Zeng
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China
| | - Xiu-E Xu
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, China
| | - Wang-Kai Fang
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China
| | - En-Min Li
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Department of Biochemistry and Molecular Biology, Shantou University Medical College, Shantou 515041, China.
| | - Li-Yan Xu
- The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan Area, Shantou University Medical College, Shantou 515041, China; Institute of Oncologic Pathology, Shantou University Medical College, Shantou 515041, China.
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16
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Urinary neutrophil gelatinase-associated lipocalin as an early predictor of disease severity and mortality in acute pancreatitis. Pancreas 2015; 44:448-52. [PMID: 25426620 DOI: 10.1097/mpa.0000000000000282] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
OBJECTIVES In reference to our earlier publication, laboratory tests that reflect severe intravascular volume depletion can be used for predicting the severity of acute pancreatitis (AP). The aim of the study was to assess whether urinary level of neutrophil gelatinase-associated lipocalin (NGAL) could represent a useful marker of AP severity. METHODS We observed a cohort of 104 prospectively enrolled patients. The patients were classified into 3 groups: mild AP, moderately severe AP, and severe AP. Urine samples were collected on admission (NGAL-as) and during the first 24 hours (NGAL-first day) for examination of urinary level of NGAL concentrations from the first day. RESULTS Acute pancreatitis was considered severe in 16 (15%) patients, moderately severe in 25 (24%) patients, and mild in 63 (61%) patients.There were statistically significant trends for an increase in severity (P = 0.04, P = 0.003) and mortality (P < 0.031, P = 0.01) with raising NGAL-as and NGAL-first day concentrations, respectively. The areas under the curve for severity predicted by NGAL-as and NGAL-first day were 0.75 and 0.93, respectively. The areas under the curve for mortality prediction by NGAL-as and NGAL-first day were 0.980 and 0.92, respectively. CONCLUSIONS The urinary level of NGAL is a promising new diagnostic and prognostic factor for severe AP in an early stage of the disease.
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17
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Diverse functional roles of lipocalin-2 in the central nervous system. Neurosci Biobehav Rev 2015; 49:135-56. [DOI: 10.1016/j.neubiorev.2014.12.006] [Citation(s) in RCA: 137] [Impact Index Per Article: 13.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2014] [Revised: 11/28/2014] [Accepted: 12/04/2014] [Indexed: 12/16/2022]
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Candido S, Maestro R, Polesel J, Catania A, Maira F, Signorelli SS, McCubrey JA, Libra M. Roles of neutrophil gelatinase-associated lipocalin (NGAL) in human cancer. Oncotarget 2015; 5:1576-94. [PMID: 24742531 PMCID: PMC4039233 DOI: 10.18632/oncotarget.1738] [Citation(s) in RCA: 86] [Impact Index Per Article: 8.6] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Cancer remains one of the major cause of death in the Western world. Although, it has been demonstrated that new therapies can improve the outcome of cancer patients, still many patients relapse after treatment. Therefore, there is a need to identify novel factors involved in cancer development and/or progression. Recently, neutrophil gelatinase-associated lipocalin (NGAL) has been suggested as a key player in different cancer types. Its oncogenic effect may be related to the complex NGAL/MMP-9. In the present study, NGAL was analyzed at both transcript and protein levels in different cancer types by analysing 38 public available microarray datasets and the Human Protein Atlas tool. NGAL transcripts were significantly higher in the majority of solid tumors compared to the relative normal tissues for every dataset analyzed. Furthermore, concordance of NGAL at both mRNA and protein levels was observed for 6 cancer types including bladder, colorectal, liver, lung, ovarian, and pancreatic. All metastatic tumors showed a decrease of NGAL expression when compared to matched primary lesions. According to these results, NGAL is a candidate marker for tumor growth in a fraction of solid tumors. Further investigations are required to elucidate the function of NGAL in tumor development and metastatic processes.
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Affiliation(s)
- Saverio Candido
- Department of Bio-medical Sciences, Section of Pathology and Oncology, Laboratory of Translational Oncology and Functional Genomics, University of Catania, Catania, (Italy)
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Nicastri A, Gaspari M, Sacco R, Elia L, Gabriele C, Romano R, Rizzuto A, Cuda G. N-glycoprotein analysis discovers new up-regulated glycoproteins in colorectal cancer tissue. J Proteome Res 2014; 13:4932-41. [PMID: 25247386 DOI: 10.1021/pr500647y] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
Colorectal cancer is one of the leading causes of death due to cancer worldwide. Therefore, the identification of high-specificity and -sensitivity biomarkers for the early detection of colorectal cancer is urgently needed. Post-translational modifications, such as glycosylation, are known to play an important role in cancer progression. In the present work, we used a quantitative proteomic technique based on (18)O stable isotope labeling to identify differentially expressed N-linked glycoproteins in colorectal cancer tissue samples compared with healthy colorectal tissue from 19 patients undergoing colorectal cancer surgery. We identified 54 up-regulated glycoproteins in colorectal cancer samples, therefore potentially involved in the biological processes of tumorigenesis. In particular, nine of these (PLOD2, DPEP1, SE1L1, CD82, PAR1, PLOD3, S12A2, LAMP3, OLFM4) were found to be up-regulated in the great majority of the cohort, and, interestingly, the association with colorectal cancer of four (PLOD2, S12A2, PLOD3, CD82) has not been hitherto described.
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Affiliation(s)
- Annalisa Nicastri
- Proteomics@UMG, Department of Experimental and Clinical Medicine and ‡Surgery Unit, Department of Experimental and Clinical Medicine, Magna Graecia University of Catanzaro , viale Europa, 88100 Catanzaro, Italy
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Lippi G, Meschi T, Nouvenne A, Mattiuzzi C, Borghi L. Neutrophil gelatinase-associated lipocalin in cancer. Adv Clin Chem 2014; 64:179-219. [PMID: 24938019 DOI: 10.1016/b978-0-12-800263-6.00004-5] [Citation(s) in RCA: 36] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022]
Abstract
Neutrophil gelatinase-associated lipocalin (NGAL), also known as lipocalin-2, is a 178-amino acid protein which exists in three molecular forms, including a 25-kDa monomer, a 45-kDa homodimer, and a 135-kDa heterodimer complexed with matrix metalloproteinase 9 (MMP-9). Polymorphonuclear neutrophils and tubular cells of the kidney are the most representative cellular sources. As such, NGAL is now considered the biochemical gold standard for early diagnosis of acute kidney injury. Recent evidence suggests, however, that ectopic or enhanced expression of NGAL may occur in many other pathologic conditions including cancer. Several epidemiologic studies, as reviewed in this chapter, showed that a variety of malignant tumors consistently overexpressed NGAL with increased concentration in blood, urine, and other biologic fluids. In addition, NGAL was frequently associated with tumor size, stage, and invasiveness. These features thus make it a potential biomarker for malignancy. A number of experimental studies also demonstrated that the ability to bind MMP-9, to scavenge iron into cancer cells along with the effect on subcellular localization of transmembrane proteins such as cadherins and catenins, confers this protein the potential to enhance can cer aggressiveness and makes it an appealing target of future anticancer research.
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Marti J, Fuster J. Prognostic value of serum neutrophil gelatinase-associated lipocalin in metastatic and non-metastatic colorectal cancer: reply. World J Surg 2014; 37:2729. [PMID: 23887597 DOI: 10.1007/s00268-013-2166-7] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Affiliation(s)
- Josep Marti
- Liver and Surgery and Transplantation Unit, Hospital Clinic i Provincial, Barcelona, Spain,
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Maier HT, Aigner F, Trenkwalder B, Zitt M, Vallant N, Perathoner A, Margreiter C, Moser P, Pratschke J, Amberger A. Up-regulation of Neutrophil Gelatinase-Associated Lipocalin in Colorectal Cancer Predicts Poor Patient Survival. World J Surg 2014; 38:2160-7. [DOI: 10.1007/s00268-014-2499-x] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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Kaur S, Sharma N, Krishn SR, Lakshmanan I, Rachagani S, Baine MJ, Smith LM, Lele SM, Sasson AR, Guha S, Mallya K, Anderson JM, Hollingsworth MA, Batra SK. MUC4-mediated regulation of acute phase protein lipocalin 2 through HER2/AKT/NF-κB signaling in pancreatic cancer. Clin Cancer Res 2014; 20:688-700. [PMID: 24240113 PMCID: PMC3946494 DOI: 10.1158/1078-0432.ccr-13-2174] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
PURPOSE MUC4 shows aberrant expression in early pancreatic lesions and a high specificity for pancreatic cancer. It thus has a high potential to be a sensitive and specific biomarker. Unfortunately, its low serum level limits its diagnostic/prognostic potential. We here report that a multifaceted acute phase protein lipocalin 2, regulated by MUC4, could be a potential diagnostic/prognostic marker for pancreatic cancer. Experimental Designs and RESULTS Overexpression/knockdown, luciferase reporter and molecular inhibition studies revealed that MUC4 regulates lipocalin 2 by stabilizing HER2 and stimulating AKT, which results in the activation of NF-κB. Immunohistochemical analyses of lipocalin 2 and MUC4 showed a significant positive correlation between MUC4 and lipocalin 2 in primary, metastatic tissues (Spearman correlation coefficient 0.71, P = 0.002) from rapid autopsy tissue sample from patients with pancreatic cancer as well as in serum and tissue samples from spontaneous KRASG(12)D mouse pancreatic cancer model (Spearman correlation coefficient 0.98, P < 0.05). Lipocalin 2 levels increased progressively with disease advancement (344.2 ± 22.8 ng/mL for 10 weeks to 3067.2 ± 572.6 for 50 weeks; P < 0.0001). In human pancreatic cancer cases, significantly elevated levels of lipocalin 2 were observed in patients with pancreatic cancer (148 ± 13.18 ng/mL) in comparison with controls (73.27 ± 4.9 ng/mL, P = 0.014). Analyses of pre- and postchemotherapy patients showed higher lipocalin 2 levels in prechemotherapy patients [121.7 ng/mL; 95% confidence interval (CI), 98.1-150.9] in comparison with the postchemotherapy (92.6 ng/mL; 95% CI, 76.7-111.6; P = 0.06) group. CONCLUSIONS This study delineates the association and the downstream mechanisms of MUC4-regulated elevation of lipocalin-2 (via HER2/AKT/NF-κB) and its clinical significance for prognosis of pancreatic cancer.
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Affiliation(s)
- Sukhwinder Kaur
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Neil Sharma
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Shiv Ram Krishn
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Imay Lakshmanan
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Satyanarayana Rachagani
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Michael J. Baine
- Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA
| | - Lynette M. Smith
- Department of Statistics, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Subodh M. Lele
- Department of Pathology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Aaron R. Sasson
- Department of Surgery, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Sushovan Guha
- Division of Gastroenterology, Hepatology and Nutrition, UT Health-UT Health Science Center and Medical School at Houston, Houston, Texas, USA
| | - Kavita Mallya
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA
| | - Judy M. Anderson
- Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA
| | - Michael A. Hollingsworth
- Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA
| | - Surinder K. Batra
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, Nebraska, USA
- Department of Pathology, University of Nebraska Medical Center, Omaha, Nebraska, USA
- Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, NE, USA
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Itenov TS, Bangert K, Christensen PH, Jensen JU, Bestle MH. Serum and plasma neutrophil gelatinase associated lipocalin (NGAL) levels are not equivalent in patients admitted to intensive care. J Clin Lab Anal 2014; 28:163-7. [PMID: 24395189 DOI: 10.1002/jcla.21662] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/13/2013] [Accepted: 06/24/2013] [Indexed: 01/24/2023] Open
Abstract
BACKGROUND Neutrophil gelatinase associated lipocalin (NGAL) is proposed as a biomarker of acute kidney injury (AKI). NGAL has been studied in a range of body fluids including serum and EDTA plasma. The aim of the present study was to establish relationship between serum NGAL concentrations and EDTA plasma NGAL concentrations in patients admitted to intensive care units (ICUs) and whether these determinations are directly comparable in this setting. METHODS NGAL was measured in 40 paired samples of serum and EDTA plasma from 25 patients admitted to intensive care with a commercial particle-enhanced turbidimetric immunoassay (The NGAL Test™, BioPorto Diagnostics A/S, Gentofte, Denmark) on a Roche Hitachi 917 (Roche-Hitachi, Inc., Tokyo, Japan) analyzer. RESULTS Serum NGAL concentrations ranged from 26.8 to 1,808 ng/ml (median 281 ng/ml, interquartile range (IQR) 453 ng/ml). EDTA plasma NGAL concentrations ranged from 25.7 to 1,752 ng/ml (median 225 ng/ml, IQR 352 ng/ml). The difference in NGAL concentrations in paired serum and EDTA plasma samples (serum- plasma) ranged from -13.8 to 321 ng/ml (median 79 ng/ml, IQR 116 ng/ml; difference from zero, P < 0.0001, Wilcoxon's signed rank test). Although serum and EDTA plasma values were correlated (Spearman's r = 0.95, P < 0.0001), Deming regression analysis showed a slope of 1.1 that was not significantly different from unity (95% confidence interval (CI) 1.0-1.1) and a highly significant intercept of 67.9 ng/ml with a wide confidence interval (95% CI 29.8-106). CONCLUSION NGAL concentration values measured in serum and EDTA plasma cannot be directly compared and should not be used as equivalents in studies of patients admitted to intensive care.
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Affiliation(s)
- Theis Skovsgaard Itenov
- Department of Anesthesiology, Nordsjaellands Hospital, Copenhagen University Hospital, Hillerød, Denmark
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Neutrophil Gelatinase-Associated Lipocalin and Its Influence on Tumor Progression in Systemic Malignancies. World J Surg 2013; 37:2727-8. [DOI: 10.1007/s00268-013-2131-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
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