Tumor-associated metabolic and inflammatory responses in early stage non-small cell lung cancer: Local patterns and prognostic significance

Millares, Laura; Barreiro Portela, Esther; Cortes, Roldan; Martínez-Romero, Anabel; Balcells Nadal, Cristina; Cascante Serratosa, Marta; Enguita, Ana Belen; Álvarez, Carlos; Rami-Porta, Ramón; Sánchez de Cos, Julio; Seijo, Luis; Monsó Molas, Eduard; Grupo Colaborativo en Cáncer de Pulmón CIBERES-CIBERONC-SEPAR-Plataforma Biobanco Pulmonar

doi:http://dx.doi.org/10.1016/j.lungcan.2018.06.015

Tumor-associated metabolic and inflammatory responses in early stage non-small cell lung cancer: Local patterns and prognostic significance

Citation

Millares L, Barreiro E, Cortes R, Martinez-Romero A, Balcells C, Cascante M et al. Tumor-associated metabolic and inflammatory responses in early stage non-small cell lung cancer: Local patterns and prognostic significance. Lung Cancer. 2018 Aug;122:124-30. DOI: 10.1016/j.lungcan.2018.06.015

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.