Laura Millares1, Esther Barreiro2, Roldan Cortes3, Anabel Martinez-Romero4, Cristina Balcells5, Marta Cascante6, Ana Belen Enguita7, Carlos Alvarez8, Ramón Rami-Porta9, Julio Sánchez de Cos10, Luis Seijo11, Eduard Monsó12. 1. Fundació Parc Taulí- Institut d' Investigació i Innovació Parc Taulí (I3PT), Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Universitat Autònoma de Barcelona, Esfera UAB, Barcelona, Spain. Electronic address: lmillares@tauli.cat. 2. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Pulmonology Department-Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, IMIM-Hospital del Mar, Parc de Salut Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), Barcelona, Spain. Electronic address: ebarreiro@imim.es. 3. Institut de Biomedicina (IBUB), Universitat de Barcelona, Spain; Department of Biochemistry and Molecular Biology, Faculty of Biology, and IDIBAPS, Unit Associated with CSIC, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Electronic address: roldancg@gmail.com. 4. Pulmonology Department-Muscle Wasting and Cachexia in Chronic Respiratory Diseases and Lung Cancer Research Group, IMIM-Hospital del Mar, Parc de Salut Mar, Health and Experimental Sciences Department (CEXS), Universitat Pompeu Fabra (UPF), Barcelona Biomedical Research Park (PRBB), Barcelona, Spain. Electronic address: anabelmr.94@hotmail.es. 5. Institut de Biomedicina (IBUB), Universitat de Barcelona, Spain; Department of Biochemistry and Molecular Biology, Faculty of Biology, and IDIBAPS, Unit Associated with CSIC, Barcelona, Spain. Electronic address: crisgatsu@gmail.com. 6. Institut de Biomedicina (IBUB), Universitat de Barcelona, Spain; Department of Biochemistry and Molecular Biology, Faculty of Biology, and IDIBAPS, Unit Associated with CSIC, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III (ISCIII), Madrid, Spain. Electronic address: martacascante@ub.edu. 7. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Pathology, Hospital 12 Octubre, Madrid, Spain. Electronic address: abenguita@hotmail.com. 8. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Respiratory Medicine, Hospital 12 Octubre, Madrid, Spain. Electronic address: carlosjose.alvarez@salud.madrid.org. 9. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Thoracic Surgery, Hospital Universitario Mutua de Terrassa, Barcelona, Spain. Electronic address: rramip@yahoo.es. 10. Department of Respiratory Medicine, Hospital San Pedro de Alcántara, Caceres, Spain. Electronic address: juli1949@separ.es. 11. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Respiratory Medicine, Universidad de Navarra, Madrid, Spain. Electronic address: lseijo@unav.es. 12. Centro de Investigación Biomédica en Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III (ISCIII), Madrid, Spain; Department of Respiratory Medicine, Hospital Universitario Parc Taulí, Barcelona, Spain; Department of Medicine, Universitat Autònoma de Barcelona (UAB), Barcelona, Spain. Electronic address: emonso@tauli.cat.
Abstract
INTRODUCTION: Non-small cell lung cancer (NSCLC) patients diagnosed in early stage and surgically-treated have five-year mortality rate >20%. The identification of biomarkers able to predict progression and death may help to identify patients needing closer follow-up. METHODS: A retrospective cohort of early-stage surgically-treated NSCLC patients enrolled in the International Association for the Study of Lung Cancer (IASLC) Staging Project was created, and tissue Microarrays (TMAs) were constructed with tumor and non-tumor lung tissue. Pentose phosphate pathway (PPP) proteins (transketolase [TKT] and transketolase-like 1 [TKTL1]), inflammatory markers (cyclooxygenase-2 [COX-2], tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL1β], nuclear factor kappa-light-chain-enhancer of activated B cells [NFκB]-p65 and antigen Ki-67), and programmed death-ligand 1 (PDL1) were measured by immunohistochemistry. RESULTS: NSCLC patients with adenocarcinoma (ADC) or squamous cell carcinoma (SCC) were included in the study (n = 199). TKT and TKTL1 were significantly higher in ADC than in non-tumor tissue (p < 0.001). Higher values were also observed in NSCLC for all the inflammatory markers, with figures >30% above those of non-tumor tissue (p < 0.001). PDL1 analysis showed a higher percentage of positivity in ADC than in non-tumor tissue (p < 0.001). Multivariate Cox proportional hazards modeling confirmed that high IL1β level in tumor tissue was independently associated with 3-year mortality in NSCLC [HR = 2.05, 95% CI (1.1-3.7), p = 0.019], a relationship driven by ADC subtype. CONCLUSION: This study confirms an increase in metabolic activity and an inflammatory response in tumor tissue of early stage NSCLC, and a significant relationship between high levels of IL1β in the tumor and poor prognosis in ADC.
INTRODUCTION:Non-small cell lung cancer (NSCLC) patients diagnosed in early stage and surgically-treated have five-year mortality rate >20%. The identification of biomarkers able to predict progression and death may help to identify patients needing closer follow-up. METHODS: A retrospective cohort of early-stage surgically-treated NSCLCpatients enrolled in the International Association for the Study of Lung Cancer (IASLC) Staging Project was created, and tissue Microarrays (TMAs) were constructed with tumor and non-tumor lung tissue. Pentose phosphate pathway (PPP) proteins (transketolase [TKT] and transketolase-like 1 [TKTL1]), inflammatory markers (cyclooxygenase-2 [COX-2], tumor necrosis factor alpha [TNF-α], interleukin 1 beta [IL1β], nuclear factor kappa-light-chain-enhancer of activated B cells [NFκB]-p65 and antigen Ki-67), and programmed death-ligand 1 (PDL1) were measured by immunohistochemistry. RESULTS:NSCLCpatients with adenocarcinoma (ADC) or squamous cell carcinoma (SCC) were included in the study (n = 199). TKT and TKTL1 were significantly higher in ADC than in non-tumor tissue (p < 0.001). Higher values were also observed in NSCLC for all the inflammatory markers, with figures >30% above those of non-tumor tissue (p < 0.001). PDL1 analysis showed a higher percentage of positivity in ADC than in non-tumor tissue (p < 0.001). Multivariate Cox proportional hazards modeling confirmed that high IL1β level in tumor tissue was independently associated with 3-year mortality in NSCLC [HR = 2.05, 95% CI (1.1-3.7), p = 0.019], a relationship driven by ADC subtype. CONCLUSION: This study confirms an increase in metabolic activity and an inflammatory response in tumor tissue of early stage NSCLC, and a significant relationship between high levels of IL1β in the tumor and poor prognosis in ADC.
Authors: Bo Yuan; Michael J Clowers; Walter V Velasco; Stephen Peng; Qian Peng; Yewen Shi; Marco Ramos-Castaneda; Melody Zarghooni; Shuanying Yang; Rachel L Babcock; Seon Hee Chang; John V Heymach; Jianjun Zhang; Edwin J Ostrin; Stephanie S Watowich; Humam Kadara; Seyed Javad Moghaddam Journal: JCI Insight Date: 2022-06-08
Authors: Giuseppe Luigi Banna; Alex Friedlaender; Marco Tagliamento; Veronica Mollica; Alessio Cortellini; Sara Elena Rebuzzi; Arsela Prelaj; Abdul Rafeh Naqash; Edouard Auclin; Lucia Garetto; Laura Mezquita; Alfredo Addeo Journal: Curr Oncol Rep Date: 2022-10-18 Impact factor: 5.945
Authors: Rui Li; Stephanie L Ong; Linh M Tran; Zhe Jing; Bin Liu; Stacy J Park; Zi Ling Huang; Tonya C Walser; Eileen L Heinrich; Gina Lee; Ramin Salehi-Rad; William P Crosson; Paul C Pagano; Manash K Paul; Shili Xu; Harvey Herschman; Kostyantyn Krysan; Steven Dubinett Journal: Sci Rep Date: 2020-01-15 Impact factor: 4.379