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Illini O, Benej M, Lang-Stöberl AS, Fabikan H, Brcic L, Sucher F, Krenbek D, Krajc T, Weinlinger C, Hochmair MJ, Valipour A, Klikovits T, Watzka S. Prognostic Value of PD-L1, BAP-1 and ILK in Pleural Mesothelioma. J Clin Med 2024; 13:7322. [PMID: 39685780 DOI: 10.3390/jcm13237322] [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: 10/31/2024] [Revised: 11/24/2024] [Accepted: 11/27/2024] [Indexed: 12/18/2024] Open
Abstract
Background: Pleural mesothelioma (PM) is a rare type of cancer with poor prognosis. Prognostic and predictive biomarkers could improve treatment strategies in these patients. Programmed death ligand 1 (PD-L1), integrin-linked kinase (ILK) and breast cancer gene 1-associated protein (BAP-1) have been proposed to predict outcomes in PM, but existing data are limited and controversial. Design and Methods: This single-center, retrospective study analyzed data on expression patterns and the prognostic role of PD-L1, ILK and BAP-1 in consecutive patients diagnosed with PM. Results: Of all patients (n = 52) included, more than half showed a positive PD-L1 expression (52% TPS ≥ 1%, 65% CPS ≥ 1), 69% showed a BAP-1 loss and 80% an ILK ≥ 50%. Positive PD-L1 expression was more frequent in the non-epithelioid subtype (p = 0.045). ILK intensity (p = 0.032) and positive PD-L1 (p = 0.034) were associated with more advanced tumor stages. The median overall survival (OS) was 16.9 (95% CI 13.1-25.2) months. Multimodality therapy (MMT) including surgery and early stage were independent prognostic factors for longer OS (MMT: HR 0.347, 95% CI 0.13-0.90, p = 0.029; advanced stage: HR 4.989; 95% CI 1.64-15.13, p = 0.005). Patients with an expression of PD-L1 TPS ≥ 1% or BAP-1 positivity showed numerically worse survival with a median OS of 15.3 (11.5; 24.4) vs. 20.0 (11.2; 34.9) and 11.3 (5.6; 31.0) vs. 20.0 (15.2; 28.1) months, respectively. Furthermore, PD-L1 was associated with worse survival in patients receiving MMT (PD-L1 TPS ≥ 1%: 15.8 (12.1-25.4) vs. 31.3 (17.4-95.4) p = 0.053). ILK expression ≥50% did not influence survival. The combinations of CPS ≥ 1% with BAP-1 positivity or ILK expression ≥50% were associated with worse survival (p = 0.045, p = 0.019). Conclusions: In this real-world analysis, expressions of PD-L1 and BAP-1 were associated with worse survival in patients with PM. ILK showed no prognostic value. Further studies with larger cohorts are needed to identify prognostic and predictive biomarkers facilitating optimized individual treatment decision in this rare type of cancer.
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Affiliation(s)
- Oliver Illini
- Department of Respiratory and Critical Care Medicine, Clinic Floridsdorf, Vienna Healthcare Group, 1130 Vienna, Austria
- Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Clinic Floridsdorf, 1210 Vienna, Austria
| | - Michal Benej
- Department of Thoracic Surgery, Clinic Floridsdorf, Vienna Healthcare Group, 1210 Vienna, Austria
- Karl Landsteiner Institute for Clinical and Translational Thoracic Surgery Research, Clinic Floridsdorf, 1210 Vienna, Austria
| | - Anna Sophie Lang-Stöberl
- Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Clinic Floridsdorf, 1210 Vienna, Austria
| | - Hannah Fabikan
- Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Clinic Floridsdorf, 1210 Vienna, Austria
| | - Luka Brcic
- Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria
| | - Florian Sucher
- Diagnostic and Research Institute of Pathology, Medical University of Graz, 8010 Graz, Austria
| | - Dagmar Krenbek
- Department of Pathology, Clinic Floridsdorf, Vienna Healthcare Group, 1210 Vienna, Austria
| | - Tibor Krajc
- Department of Thoracic Surgery, Clinic Floridsdorf, Vienna Healthcare Group, 1210 Vienna, Austria
- Karl Landsteiner Institute for Clinical and Translational Thoracic Surgery Research, Clinic Floridsdorf, 1210 Vienna, Austria
| | - Christoph Weinlinger
- Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Clinic Floridsdorf, 1210 Vienna, Austria
| | - Maximilian J Hochmair
- Department of Respiratory and Critical Care Medicine, Clinic Floridsdorf, Vienna Healthcare Group, 1130 Vienna, Austria
- Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Clinic Floridsdorf, 1210 Vienna, Austria
| | - Arschang Valipour
- Department of Respiratory and Critical Care Medicine, Clinic Floridsdorf, Vienna Healthcare Group, 1130 Vienna, Austria
- Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Clinic Floridsdorf, 1210 Vienna, Austria
| | - Thomas Klikovits
- Department of Thoracic Surgery, Clinic Floridsdorf, Vienna Healthcare Group, 1210 Vienna, Austria
- Karl Landsteiner Institute for Clinical and Translational Thoracic Surgery Research, Clinic Floridsdorf, 1210 Vienna, Austria
| | - Stefan Watzka
- Department of Thoracic Surgery, Clinic Floridsdorf, Vienna Healthcare Group, 1210 Vienna, Austria
- Karl Landsteiner Institute for Clinical and Translational Thoracic Surgery Research, Clinic Floridsdorf, 1210 Vienna, Austria
- Paracelsus Medical University, 5020 Salzburg, Austria
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Schillebeeckx E, van Meerbeeck JP, Lamote K. Clinical utility of diagnostic biomarkers in malignant pleural mesothelioma: a systematic review and meta-analysis. Eur Respir Rev 2021; 30:30/162/210057. [PMID: 34789461 PMCID: PMC9489015 DOI: 10.1183/16000617.0057-2021] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2021] [Accepted: 06/08/2021] [Indexed: 02/06/2023] Open
Abstract
Malignant pleural mesothelioma (MPM) is characterised by late-stage diagnosis and poor prognosis. Currently, no screening tool is advocated and diagnosis is based on invasive techniques, which are not well tolerated. Non-invasive diagnostic biomarkers have shown potential and could have a huge clinical benefit. However, despite extensive research, there is no consensus yet on their clinical use, with many articles reporting contradicting results, limiting their clinical implementation. The aim of this systematic review is therefore to explore the different semi- and non-invasive diagnostic markers in several human matrices and identify those that might clinically be relevant. A total of 100 articles were selected through Web of Science and PubMed, with 56 articles included in the quantitative analysis. Although many studies have reported on the diagnostic accuracy of MPM biomarkers such as serum mesothelin and high-mobility group box protein 1 and plasma fibulin-3, none have resulted in a validated test for early detection. Future research should focus on external validation, combinations into biomarker panels, the inclusion of early stage MPM patients and a combination of different biomarker matrices, as well as new markers. Diagnostic biomarkers for malignant pleural mesothelioma seem promising; however, further research is necessary to prove their clinical value. This review provides a thorough overview of the different markers and compares them in several matrices.https://bit.ly/35ni6UO
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Affiliation(s)
- Eline Schillebeeckx
- Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Wilrijk, Belgium .,Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, Belgium
| | - Jan P van Meerbeeck
- Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Wilrijk, Belgium.,Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, Belgium.,Dept of Internal Medicine, Ghent University, Ghent, Belgium.,Pulmonology and Thoracic Oncology, Antwerp University Hospital, Edegem, Belgium.,European Reference Network for rare respiratory diseases (ERN-LUNG), Frankfurt Am Main, Germany
| | - Kevin Lamote
- Laboratory of Experimental Medicine and Pediatrics, University of Antwerp, Wilrijk, Belgium.,Infla-Med Centre of Excellence, University of Antwerp, Wilrijk, Belgium.,Dept of Internal Medicine, Ghent University, Ghent, Belgium
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3
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Opitz I, Scherpereel A, Berghmans T, Psallidas I, Glatzer M, Rigau D, Astoul P, Bölükbas S, Boyd J, Coolen J, De Bondt C, De Ruysscher D, Durieux V, Faivre-Finn C, Fennell DA, Galateau-Salle F, Greillier L, Hoda MA, Klepetko W, Lacourt A, McElnay P, Maskell NA, Mutti L, Pairon JC, Van Schil P, van Meerbeeck JP, Waller D, Weder W, Putora PM, Cardillo G. ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma. Eur J Cardiothorac Surg 2021; 58:1-24. [PMID: 32448904 DOI: 10.1093/ejcts/ezaa158] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009-2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally via image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including BAP-1 and CDKN2A (p16) for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pretherapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasize that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.
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Affiliation(s)
- Isabelle Opitz
- Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
| | - Arnaud Scherpereel
- Department of Pulmonary and Thoracic Oncology, French National Network of Clinical Expert Centers for Malignant Pleural Mesothelioma Management (Mesoclin), Lille, France.,Department of Pulmonary and Thoracic Oncology, University Lille, CHU Lille, INSERM U1189, OncoThAI, Lille, France
| | | | - Ioannis Psallidas
- Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Markus Glatzer
- Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland
| | - David Rigau
- Iberoamerican Cochrane Center, Barcelona, Spain
| | - Philippe Astoul
- Department of Thoracic Oncology, Pleural Diseases and Interventional Pulmonology, Hôpital Nord, Aix-Marseille University, Marseille, France
| | - Servet Bölükbas
- Department of Thoracic Surgery, Evang, Kliniken Essen-Mitte, Essen, Germany
| | | | - Johan Coolen
- Department of Imaging and Pathology, KU Leuven, Leuven, Belgium
| | - Charlotte De Bondt
- Department of Pulmonology and Thoracic Oncology, Antwerp University and Antwerp University Hospital, Antwerp, Belgium
| | - Dirk De Ruysscher
- Department of Radiation Oncology (Maastro Clinic), Maastricht University Medical Center+, GROW Research Institute, Maastricht, Netherlands
| | - Valerie Durieux
- Bibliothèque des Sciences de la Santé, Université Libre de Bruxelles (ULB), Brussels, Belgium
| | - Corinne Faivre-Finn
- The Christie NHS Foundation Trust, The University of Manchester, Manchester, UK
| | - Dean A Fennell
- Leicester Cancer Research Centre, University of Leicester and University of Leicester Hospitals NHS Trust, Leicester, UK
| | - Francoise Galateau-Salle
- Department of Biopathology, National Reference Center for Pleural Malignant Mesothelioma and Rare Peritoneal Tumors MESOPATH, Centre Leon Berard, Lyon, France
| | - Laurent Greillier
- Department of Multidisciplinary Oncology and Therapeutic Innovations, Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Inserm UMR1068, CNRS UMR7258, Marseille, France
| | - Mir Ali Hoda
- Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Walter Klepetko
- Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Aude Lacourt
- University Bordeaux, INSERM, Bordeaux Population Health Research Center, Team EPICENE, UMR 1219, Bordeaux, France
| | | | - Nick A Maskell
- Academic Respiratory Unit, Bristol Medical School, University of Bristol, Bristol, UK
| | - Luciano Mutti
- Teaching Hospital Vercelli/Gruppo Italiano, Vercelli, Italy
| | - Jean-Claude Pairon
- INSERM U955, GEIC2O, Université Paris-Est Créteil, Service de Pathologies professionnelles et de l'Environnement, Institut Santé -Travail Paris-Est, CHI Créteil, Créteil, France
| | - Paul Van Schil
- Department of Thoracic and Vascular Surgery, Antwerp University and Antwerp University Hospital, Antwerp, Belgium
| | - Jan P van Meerbeeck
- Department of Pulmonology and Thoracic Oncology, Antwerp University and Antwerp University Hospital, Antwerp, Belgium
| | - David Waller
- Barts Thorax Centre, St Bartholomew's Hospital, London, UK
| | - Walter Weder
- Department of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
| | - Paul Martin Putora
- Department of Radiation Oncology, Kantonsspital St. Gallen, St. Gallen, Switzerland.,Department of Radiation Oncology, University of Bern, Bern, Switzerland
| | - Giuseppe Cardillo
- Unit of Thoracic Surgery, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
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4
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Scherpereel A, Opitz I, Berghmans T, Psallidas I, Glatzer M, Rigau D, Astoul P, Bölükbas S, Boyd J, Coolen J, De Bondt C, De Ruysscher D, Durieux V, Faivre-Finn C, Fennell D, Galateau-Salle F, Greillier L, Hoda MA, Klepetko W, Lacourt A, McElnay P, Maskell NA, Mutti L, Pairon JC, Van Schil P, van Meerbeeck JP, Waller D, Weder W, Cardillo G, Putora PM. ERS/ESTS/EACTS/ESTRO guidelines for the management of malignant pleural mesothelioma. Eur Respir J 2020; 55:13993003.00953-2019. [PMID: 32451346 DOI: 10.1183/13993003.00953-2019] [Citation(s) in RCA: 139] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2019] [Accepted: 10/17/2019] [Indexed: 12/23/2022]
Abstract
The European Respiratory Society (ERS)/European Society of Thoracic Surgeons (ESTS)/European Association for Cardio-Thoracic Surgery (EACTS)/European Society for Radiotherapy and Oncology (ESTRO) task force brought together experts to update previous 2009 ERS/ESTS guidelines on management of malignant pleural mesothelioma (MPM), a rare cancer with globally poor outcome, after a systematic review of the 2009-2018 literature. The evidence was appraised using the Grading of Recommendations, Assessment, Development and Evaluation approach. The evidence syntheses were discussed and recommendations formulated by this multidisciplinary group of experts. Diagnosis: pleural biopsies remain the gold standard to confirm the diagnosis, usually obtained by thoracoscopy but occasionally via image-guided percutaneous needle biopsy in cases of pleural symphysis or poor performance status. Pathology: standard staining procedures are insufficient in ∼10% of cases, justifying the use of specific markers, including BAP-1 and CDKN2A (p16) for the separation of atypical mesothelial proliferation from MPM. Staging: in the absence of a uniform, robust and validated staging system, we advise using the most recent 2016 8th TNM (tumour, node, metastasis) classification, with an algorithm for pre-therapeutic assessment. Monitoring: patient's performance status, histological subtype and tumour volume are the main prognostic factors of clinical importance in routine MPM management. Other potential parameters should be recorded at baseline and reported in clinical trials. Treatment: (chemo)therapy has limited efficacy in MPM patients and only selected patients are candidates for radical surgery. New promising targeted therapies, immunotherapies and strategies have been reviewed. Because of limited data on the best combination treatment, we emphasise that patients who are considered candidates for a multimodal approach, including radical surgery, should be treated as part of clinical trials in MPM-dedicated centres.
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Affiliation(s)
- Arnaud Scherpereel
- Pulmonary and Thoracic Oncology, Univ. Lille, CHU Lille, INSERM U1189, OncoThAI, Lille, France .,French National Network of Clinical Expert Centers for Malignant Pleural Mesothelioma Management (Mesoclin), Lille, France
| | - Isabelle Opitz
- Dept of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
| | | | - Ioannis Psallidas
- Oxford Centre for Respiratory Medicine, Oxford University Hospitals NHS Foundation Trust, Oxford, UK
| | - Markus Glatzer
- Dept of Radiation Oncology, Kantonsspital St Gallen, St Gallen, Switzerland
| | - David Rigau
- Iberoamerican Cochrane Center, Barcelona, Spain
| | - Philippe Astoul
- Dept of Thoracic Oncology, Pleural Diseases and Interventional Pulmonology, Hôpital Nord, Aix-Marseille University, Marseille, France
| | - Servet Bölükbas
- Dept of Thoracic Surgery, Evang, Kliniken Essen-Mitte, Essen, Germany
| | | | - Johan Coolen
- Dept of Imaging and Pathology, KU Leuven, Leuven, Belgium
| | - Charlotte De Bondt
- Dept of Pulmonology and Thoracic Oncology, Antwerp University and Antwerp University Hospital, Antwerp, Belgium
| | - Dirk De Ruysscher
- Dept of Radiation Oncology (Maastro Clinic), Maastricht University Medical Center+, GROW Research Institute, Maastricht, The Netherlands
| | - Valerie Durieux
- Bibliothèque des Sciences de la Santé, Université libre de Bruxelles (ULB), Brussels, Belgium
| | - Corinne Faivre-Finn
- The Christie NHS Foundation Trust, The University of Manchester, Manchester, UK
| | - Dean Fennell
- Leicester Cancer Research Centre, University of Leicester and University of Leicester Hospitals NHS Trust, Leicester, UK
| | - Francoise Galateau-Salle
- National Reference Center for Pleural Malignant Mesothelioma and Rare Peritoneal Tumors MESOPATH, Dept of Biopathology, Centre Leon Berard, Lyon, France
| | - Laurent Greillier
- Aix Marseille University, Assistance Publique Hôpitaux de Marseille, Inserm UMR1068, CNRS UMR7258, Dept of Multidisciplinary Oncology and Therapeutic Innovations, Marseille, France
| | - Mir Ali Hoda
- Dept of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Walter Klepetko
- Dept of Thoracic Surgery, Medical University of Vienna, Vienna, Austria
| | - Aude Lacourt
- Univ. Bordeaux, INSERM, Bordeaux Population Health Research Center, team EPICENE, UMR 1219, Bordeaux, France
| | | | - Nick A Maskell
- Academic Respiratory Unit, Bristol Medical School, University of Bristol, Bristol, UK
| | - Luciano Mutti
- Teaching Hosp. Vercelli/Gruppo Italiano Mesotelioma, Italy
| | - Jean-Claude Pairon
- INSERM U955, Equipe 4, Université Paris-Est Créteil, and Service de Pathologies professionnelles et de l'Environnement, Institut Santé-Travail Paris-Est, CHI Créteil, Créteil, France
| | - Paul Van Schil
- Dept Thoracic and Vascular Surgery, Antwerp University and Antwerp University Hospital, Antwerp, Belgium
| | - Jan P van Meerbeeck
- Dept of Pulmonology and Thoracic Oncology, Antwerp University and Antwerp University Hospital, Antwerp, Belgium
| | - David Waller
- Barts Thorax Centre, St Bartholomew's Hospital, London, UK
| | - Walter Weder
- Dept of Thoracic Surgery, University Hospital Zurich, Zurich, Switzerland
| | - Giuseppe Cardillo
- Unit of Thoracic Surgery, Azienda Ospedaliera San Camillo Forlanini, Rome, Italy
| | - Paul Martin Putora
- Dept of Radiation Oncology, Kantonsspital St Gallen, St Gallen, Switzerland.,Dept of Radiation Oncology, University of Bern, Bern, Switzerland
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Shen H, Ma JL, Zhang Y, Deng GL, Qu YL, Wu XL, He JX, Zhang S, Zeng S. Integrin-linked kinase overexpression promotes epithelial-mesenchymal transition via nuclear factor-κB signaling in colorectal cancer cells. World J Gastroenterol 2016; 22:3969-3977. [PMID: 27099440 PMCID: PMC4823247 DOI: 10.3748/wjg.v22.i15.3969] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/24/2015] [Revised: 12/06/2015] [Accepted: 12/30/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate the effect of integrin-linked kinase (ILK) on proliferation, metastasis, and invasion of the colorectal cancer cell line SW480.
METHODS: In this study, the colorectal cancer cell line SW480 was stably transfected with ILK plasmids, and small interfering RNA (siRNA) was used to knockdown expression of nuclear factor (NF)-κB/p65. Methylthiazole tetrazolium (MTT) assay was performed to measure proliferation, and the wound healing migration assay and matrigel invasion assay were used to test the metastasis and invasion ability of SW480 cells. To explore the epithelial-mesenchymal transition (EMT) process, embryonic development, and the invasion and metastasis of tumors, the protein level of E-cadherin, vimentin, snail, and slug was detected by western blot. Immunofluorescence was also used to detect E-cadherin expression. Western blot was used to determine the level of phosphorylated-inhibitor of kappa B (IκB)a, inhibitor of gamma B (IγB)a, and nuclear factor kappa B (NF-κB) expressions and to explore the ILK signaling pathway.
RESULTS: Western blot results revealed that ILK expression significantly increased when ILK was overexpressed in SW480 cells (P < 0.05). Proliferation, metastasis, and invasion ability were improved in the vector-ILK group compared to the vector group (P < 0.05). Immunofluorescence results revealed that E-cadherin fluorescence intensity decreased after ILK was overexpressed (P < 0.05). Western blot results revealed that the protein expression of E-cadherin was reduced, while vimentin, snail, and slug were upregulated when ILK was overexpressed in SW480 cells (P < 0.05). In order to determine the role of the NF-κB signaling pathway in ILK overexpression promoted EMT occurrence, we overexpressed ILK in SW480 cells and found that levels of NF-κB/p65 and cytoplasmic phosphorylated-IκBa were increased and that cytoplasmic IкBa levels were decreased compared to the control group (P < 0.05). Furthermore, NF-κB/p65 knockout revealed that E-cadherin was increased in the overexpressed ILK group.
CONCLUSION: ILK overexpression improved the proliferation, metastasis, and invasion ability of SW480 cells, and this effect may be mediated by the NF-κB signaling pathway.
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Posch F, Setinek U, Flores RM, Bernhard D, Hannigan GE, Mueller MR, Watzka SB. Serum integrin-linked kinase (sILK) concentration and survival in non-small cell lung cancer: a pilot study. Clin Transl Oncol 2013; 16:455-62. [PMID: 23979911 DOI: 10.1007/s12094-013-1101-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2013] [Accepted: 08/06/2013] [Indexed: 11/29/2022]
Abstract
BACKGROUND Integrin-linked kinase (ILK) is an intracellular signaling protein critically involved in cellular growth and motility. In non-small cell lung cancer (NSCLC), increased ILK expression has been associated with decreased recurrence-free and overall survival. Recently, ILK has also been detected in the serum of NSCLC patients. OBJECTIVE To assess the prognostic impact of preoperative serum ILK (sILK) concentration on overall survival in surgically amenable NSCLC. PATIENTS AND METHODS Preoperative sILK was quantified by ELISA in 50 newly diagnosed NSCLC patients. After surgery, patients were followed-up for a median interval of 2.5 years. RESULTS Serum ILK concentrations ranged from 0 to 2.44 ng/ml. Mean sILK was around 2.3 times higher in the 16 patients who died as compared to the 34 patients who survived (1.04 vs. 0.45 ng/ml, p = 0.001). In univariate time-to-event analysis, increased sILK was associated with adverse survival [Hazard ratio (HR): 4.03, 95 % CI: 2.00-8.13, p < 0.001]. This association prevailed after multivariable adjustment for several clinical, demographic, and laboratory parameters (HR: 3.85, 95 % CI: 1.53-9.72, p = 0.004). CONCLUSIONS Serum ILK shows potential as a novel strong and independent prognostic marker for postoperative survival in surgically amenable NSCLC.
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Affiliation(s)
- F Posch
- Division of Thoracic Surgery, Karl Landsteiner Institute for Thoracic Oncology, Otto Wagner Hospital, Sanatoriumstrasse 2, 1140, Vienna, Austria
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Prazakova S, Thomas PS, Sandrini A, Yates DH. Asbestos and the lung in the 21st century: an update. CLINICAL RESPIRATORY JOURNAL 2013; 8:1-10. [PMID: 23711077 DOI: 10.1111/crj.12028] [Citation(s) in RCA: 99] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/11/2013] [Revised: 04/17/2013] [Accepted: 05/20/2013] [Indexed: 01/16/2023]
Abstract
The asbestos-related disorders (ARDs) are currently of significant occupational and public health concern. Asbestos usage has been banned in most developed countries, but asbestos is still used in many developing countries and the number of cases of ARDs worldwide is rising. Many countries are now experiencing an epidemic of ARDs that is the legacy of occupational exposure in the 1960s-1980s because of the long latency period between asbestos exposure and manifestation of disease. It is likely that asbestos-related mortality and morbidity will continue to increase. Although the most feared complications of asbestos inhalation are the malignant conditions such as mesothelioma and lung cancer, asbestos inhalation more frequently results in benign conditions such as pleural plaques, diffuse pleural thickening, and asbestosis (pulmonary fibrosis due to asbestos exposure). Over recent years, there have been changes in the epidemiology of mesothelioma, in clinical management of ARDs and developments in new techniques for early detection of malignancy. This review provides an update on the respiratory manifestations of asbestos exposure and also considers advances in screening methods that may affect future management in the workplace.
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Affiliation(s)
- Silvie Prazakova
- Faculty of Medicine, University of New South Wales, Sydney, NSW, Australia; Respiratory Medicine Department, Prince of Wales Hospital, Sydney, NSW, Australia
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