Relationship between Systemic Inflammatory Markers, GLUT1 Expression, and Maximum 18F-Fluorodeoxyglucose Uptake in Non-Small Cell Lung Carcinoma and Their Prognostic Significance

非小细胞肺癌中系统性炎症标志物、GLUT1表达和最大18F-氟代脱氧葡萄糖摄取量之间的关系及其预后意义

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Abstract

BACKGROUND: Factors involved in inflammation and cancer interact in various ways with each other, and biomarkers of systemic inflammation may have a prognostic value in cancer. Glucose transporter 1 (GLUT1) plays a pivotal role in glucose transport and metabolism and it is aberrantly expressed in various cancer types. We evaluated the differential expression of GLUT1, along with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in non-small-cell lung cancer (NSCLC), and then analyzed their prognostic significance. METHODS: A total of 163 patients with resectable NSCLC were included in this study. Tumor sections were immunohistochemically stained for GLUT1 and GLUT3. Maximum standardized uptake value (SUV(max)) was measured by preoperative FDG-PET, and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) were derived from pretreatment blood count. RESULTS: GLUT1 and GLUT3 was positively expressed in 74.8% and 6.1% of the NSCLC tissues, respectively. GLUT1 expression was significantly correlated with squamous cell carcinoma histology, poor differentiation, high pathologic stage, old age, male, smoking, and high SUV(max) (>7) (all p < 0.05). The squamous cell carcinoma and smoker group also showed significantly higher SUV(max) (both p < 0.001). Systemic inflammation markers, including NLR, PLR, and LMR, were positively correlated with high SUV(max) (all p < 0.05). High GLUT1 expression, high SUV(max), high NLR, and low LMR, were significantly associated with poor overall survival in patients with NSCLC. However, in the multivariate survival analysis, LMR was an independent prognostic factor overall (HR 1.86, 95% CI 1.05-3.3) and for the stage I/II cohort (HR 2.3, 95% CI 1.24-4.3) (all p < 0.05). CONCLUSIONS: Systemic inflammatory markers-NLR, PLR, and LMR are strongly correlated with the SUV(max) and are indicators of aggressive tumor behavior. Specifically, LMR is a promising prognostic biomarker in NSCLC patients.

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