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      Serum Levels of Kisspeptin Are Elevated in Patients with Pancreatic Cancer

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          Abstract

          Pancreatic adenocarcinoma (PDAC) still represents a devastating disease associated with a very limited survival. Novel biomarkers allowing an early diagnosis as well as an optimal selection of suitable treatment options for individual patients are urgently needed to improve the dismal outcome of PDAC patients. Recently, alterations of Kisspeptin serum levels, a member of the adipokine family, were described in various types of cancers. However, the role of circulating Kisspeptin as a biomarker in PDAC patients is poorly defined. In this study, we measured Kisspeptin serum levels in a cohort of 128 prospectively enrolled PDAC patients undergoing surgical resection as well as 36 healthy controls. Kisspeptin concentrations were elevated in PDAC patients compared to control samples. Nevertheless, Kisspeptin serum levels were independent of tumor-related factors such as the tumor grading, TNM stage, or clinical features such as the ECOG performance status. Finally, in our analysis, neither preoperative nor postoperative Kisspeptin levels turned out as a significant predictor of overall survival after tumor resection. In conclusion, our data suggest that Kisspeptin concentrations are altered in PDAC patients but do not allow to predict patients' outcome after resection of PDAC.

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          Circulating soluble urokinase plasminogen activator receptor is stably elevated during the first week of treatment in the intensive care unit and predicts mortality in critically ill patients

          Alexander Koch, Sebastian Voigt, Carsten Kruschinski … (2011)
          Introduction suPAR is the soluble form of the urokinase plasminogen activator receptor (uPAR), which is expressed in various immunologically active cells. High suPAR serum concentrations are suggested to reflect the activation of the immune system in circumstances of inflammation and infection, and have been associated with increased mortality in different populations of non-intensive care patients. In this study we sequentially analyzed suPAR serum concentrations within the first week of intensive care in a large cohort of well characterized intensive care unit (ICU) patients, in order to investigate potential regulatory mechanisms and evaluate the prognostic significance in critically ill patients. Methods A total of 273 patients (197 with sepsis, 76 without sepsis) were studied prospectively upon admission to the medical intensive care unit (ICU), on Day 3 and Day 7, and compared to 43 healthy controls. Clinical data, various laboratory parameters as well as investigational inflammatory cytokine profiles were assessed. Patients were followed for approximately one year. Results Upon admission to the ICU suPAR serum concentrations were elevated in critically ill patients as compared with healthy controls. In sepsis patients suPAR levels were higher than in non-sepsis patients (with or without systemic inflammatory response syndrome (SIRS)). During the first week after admission to the ICU serum suPAR concentrations remained stably elevated. suPAR serum concentrations measured upon admission were closely and independently correlated to various laboratory parameters, specifically biomarkers of inflammation (tumor necrosis factor (TNF), C-reactive protein (CRP)), hepatic and renal dysfunction. High suPAR levels at admission and at Day 3 were a strong independent predictor for both ICU and long-term mortality in critically ill patients. Conclusions In sepsis and non-sepsis patients suPAR serum concentrations are increased upon admission to the ICU, likely reflecting the activation state of the immune system, and remain stably elevated in the initial course of treatment. Low suPAR levels are a positive predictor of ICU- and overall survival in critically ill patients, including sepsis and non-sepsis patients. Aside from its value as a promising new prognostic biomarker, both experimental and clinical studies are required in order to understand the specific effects and regulatory mechanisms of suPAR in SIRS and sepsis, and may reveal new therapeutic options.
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            Suppression of metastasis in human breast carcinoma MDA-MB-435 cells after transfection with the metastasis suppressor gene, KiSS-1.

            Joshua D Welch, Hyun Sil Lee (1997)
            Based on the observation that chromosome 1q deletions are not infrequent in late-stage human breast carcinomas, we tested whether the recently discovered human melanoma metastasis suppressor gene, KiSS-1, which maps to chromosome 1q32-q41, could suppress metastasis of the human breast carcinoma cell line MDA-MB-435. Parental, vector-only transfectants and KiSS-1 transfectant clones were injected into the mammary fat pads of athymic nude mice and assessed for tumor growth and spontaneous metastasis to regional lymph nodes and lungs. Expression of KiSS-1 reduced metastatic potential by 95% compared to control cells but did not suppress tumorigenicity. Metastasis suppression correlated with a decreased clonogenicity in soft (0.3%) and hard (0.9%) agar. Although the overall rate of cell adhesion to extracellular matrix components was unaffected, KiSS-1 transfectants spread on immobilized type-IV collagen more rapidly than did control populations. Invasion and motility were unaffected by KiSS-1. Based on the predicted structure of the KiSS-1 protein, our results imply a mechanism whereby KiSS-1 regulates events downstream of cell-matrix adhesion, perhaps involving cytoskeletal reorganization. In addition to its already described role in melanoma, our results show that KiSS-1 also functions as a metastasis suppressor gene in at least some human breast cancers.
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              Novel Diagnostic and Predictive Biomarkers in Pancreatic Adenocarcinoma

              John C S Chang, Madappa Kundranda (2017)
              Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal disease for a multitude of reasons including very late diagnosis. This in part is due to the lack of understanding of the biological behavior of PDAC and the ineffective screening for this disease. Significant efforts have been dedicated to finding the appropriate serum and imaging biomarkers to help early detection and predict response to treatment of PDAC. Carbohydrate antigen 19-9 (CA 19-9) has been the most validated serum marker and has the highest positive predictive value as a stand-alone marker. When combined with carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA 125), CA 19-9 can help predict the outcome of patients to surgery and chemotherapy. A slew of novel serum markers including multimarker panels as well as genetic and epigenetic materials have potential for early detection of pancreatic cancer, although these remain to be validated in larger trials. Imaging studies may not correlate with elevated serum markers. Critical features for determining PDAC include the presence of a mass, dilated pancreatic duct, and a duct cut-off sign. Features that are indicative of early metastasis includes neurovascular bundle involvement, duodenal invasion, and greater post contrast enhancement. 18-F-fluorodeoxyglucose (18-FDG) radiotracer uptake and changes following treatment may predict patient overall survival following treatment. Similarly, pretreatment apparent diffusion coefficient (ADC) values may predict prognosis with lower ADC lesions having worse outcome. Although these markers have provided significant improvement in the care of pancreatic cancer patients, further advancements can be made with perhaps better combination of markers or discovery of unique marker(s) to pancreatic cancer.
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                Author and article information

                Contributors
                Tom Luedde:
                ORCID: https://orcid.org/0000-0002-6288-8821
                Journal
                Journal ID (nlm-ta): Dis Markers
                Journal ID (iso-abbrev): Dis. Markers
                Journal ID (publisher-id): DM
                Title: Disease Markers
                Publisher: Hindawi
                ISSN (Print): 0278-0240
                ISSN (Electronic): 1875-8630
                Publication date Collection: 2019
                Publication date (Electronic): 20 October 2019
                Volume: 2019
                Electronic Location Identifier: 5603474
                Affiliations
                1Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
                2Department of Internal Medicine III, University Hospital of Schleswig Holstein, Campus Kiel, Rosalind-Franklin-Str. 12, 24105 Kiel, Germany
                3Department of Visceral and Transplantation Surgery, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
                4Department of Urology, University Hospital Cologne, Cologne, Germany
                5Department of Hepatology and Gastroenterology, Charité University Medicine Berlin, Augustenburger Platz 1, 10117 Berlin, Germany
                6Department of Surgery, Maastricht University Medical Centre (MUMC), PO Box 5800, Maastricht, Netherlands
                7Division of Gastroenterology, Hepatology and Hepatobiliary Oncology, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074 Aachen, Germany
                Author notes

                Academic Editor: Sunil Hwang

                Author information
                https://orcid.org/0000-0003-3447-1161
                https://orcid.org/0000-0001-6206-0226
                https://orcid.org/0000-0003-4078-1668
                https://orcid.org/0000-0002-6288-8821
                https://orcid.org/0000-0002-2245-6362
                Article
                DOI: 10.1155/2019/5603474
                PMC ID: 6854939
                SO-VID: 87875645-e127-4eae-b90e-bc5fc5b01e1a
                Copyright © Copyright © 2019 Sven H. Loosen et al.
                License:

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Date received : 7 July 2019
                Date revision received : 4 September 2019
                Date accepted : 23 September 2019
                Funding
                Funded by: RWTH Aachen University
                Funded by: IZKF
                Funded by: Ernst-Jung-Foundation Hamburg
                Funded by: Deutsche Forschungsgemeinschaft
                Award ID: DFG RO 4317/4-1
                Award ID: LU 1360/3-1
                Award ID: SFB-TRR57/P06
                Funded by: Mildred-Scheel-Professorship
                Funded by: Deutsche Krebshilfe
                Award ID: 110043
                Funded by: H2020 European Research Council
                Award ID: 771083
                Categories
                Subject: Research Article

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