Tumor-associated metabolic and inflammatory responses in early stage non-small cell lung cancer: Local patterns and prognostic significance.
Lung Cancer
; 122: 124-130, 2018 08.
Article
em En
| MEDLINE
| ID: mdl-30032820
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 [IL1ß], 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 (nâ¯=â¯199). TKT and TKTL1 were significantly higher in ADC than in non-tumor tissue (pâ¯<â¯0.001). Higher values were also observed in NSCLC for all the inflammatory markers, with figures >30% above those of non-tumor tissue (pâ¯<â¯0.001). PDL1 analysis showed a higher percentage of positivity in ADC than in non-tumor tissue (pâ¯<â¯0.001). Multivariate Cox proportional hazards modeling confirmed that high IL1ß level in tumor tissue was independently associated with 3-year mortality in NSCLC [HRâ¯=â¯2.05, 95% CI (1.1-3.7), pâ¯=â¯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 IL1ß in the tumor and poor prognosis in ADC.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transcetolase
/
Biomarcadores Tumorais
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Carcinoma Pulmonar de Células não Pequenas
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Neoplasias Pulmonares
Tipo de estudo:
Etiology_studies
/
Incidence_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Aged
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Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Lung Cancer
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2018
Tipo de documento:
Article