RESUMO
BACKGROUND AND AIMS: While serum osteopontin (OPN)'s established role in cardiometabolic risk is recognized, its potential as a predictor of metabolic syndrome (MetS) improvement through a urine assay has not yet been demonstrated. In this study, we propose its potential predictive role over a 12-month period of standard care, with the ability to complement anthropometric measures. METHODS AND RESULTS: Hierarchical clustering revealed a notable association of urinary OPN (uOPN) with MetS criteria and overcame anthropometric measures in predicting the improvement at 12 months (OR of 2.74 [95% CI 1.32 to 6.29]). uOPN significantly contributed to the homogeneity of the nodes in the random forest and ultimately enhanced the performance of anthropometric measures when assessed for accuracy and area under the curve (AUC). CONCLUSION: Our findings offer insights into potential applications in cardiometabolic medicine for uOPN, which is easily detectable in non-invasive biological samples through an affordable assay.
Assuntos
Biomarcadores , Síndrome Metabólica , Osteopontina , Valor Preditivo dos Testes , Urinálise , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/urina , Síndrome Metabólica/sangue , Humanos , Osteopontina/urina , Osteopontina/sangue , Masculino , Feminino , Biomarcadores/urina , Biomarcadores/sangue , Pessoa de Meia-Idade , Fatores de Tempo , Adulto , Resultado do Tratamento , Idoso , Fatores de Risco CardiometabólicoRESUMO
PURPOSE: Pembrolizumab-based regimens are conditioned by the expression of PD-L1, but durable response rate is limited by innate and acquired resistance mechanisms. Here, we focus on osteopontin (OPN), an upfront biomarker of senescence, which closely associated with natural history of non-small cell lung cancer (NSCLC). METHODS: Seventy-nine patients eligible to pembrolizumab regimens-alone or in combination with chemotherapy-as first-line treatment of advanced NSCLC were enrolled. Predictive value of OPN toward iRECIST progression disease (PD) was set as first outcome. Secondary ones included performance status (ECOG) at baseline, early (first and best) responses, and overall survival (OS). RESULTS: High Serum OPN characterized patients with worse ECOG-PS (p = 0.015) at baseline and subjects experienced PD/death at first (OR 1.17 [1.02 to 1.35]; p = 0.030) and best responses (0.04 [0.00 to 0.81]; p = 0.035). OPN was associated with time-to-progression (B -2.74 [-4.46 to -1.01]) and time-to death (-0.13 [-0.20 to -0.05]). Cox regression models unveil a predictive value for iRECIST-PD (HR 1.01 [1.00 to 1.02]; p = -0.005), RECIST-PD (HR 1.01 [1.00 to 1.02]; p = 0.017), and OS (HR 1.02 [1.01 to 1.03]; p = 0.001). These models were internally validated through bootstrap resampling and characterized by relevant discrimination ability at ROC curve analyses. CONCLUSION: Baseline levels of serum OPN is closely associated with performance status and short/long term outcomes in patients with advanced NSCLC, which are candidate to pembrolizumab-based regimens. As upfront biomarker of senescence, OPN may pave the way for future studies focusing on senescence patterns in NSCLC.