Dataset Information

PD-L1 Expression Is Associated With VEGFA and LADC Patients' Survival.

ABSTRACT: Objectives: To elucidate the relationship between VEGFA and PD-L1 expression in lung adenocarcinoma (LADC). Methods: PD-L1 and VEGFA expression were determined by immunohistochemistry with H-score on formalin-fixed paraffin-embedded resected LADC specimens of 129 cases. Results: High PD-L1 expression in 53 (41.1%) patients, high VEGFA expression in 65 (50.4%), and co-expression in 18 (14.0%) were observed. Inverse correlation between expression of PD-L1 and VEGFA was found (P = 0.002, r = -0.274). VEGFA and PD-L1 expression were not significantly associated with the clinicopathological features. High PD-L1 expression was significantly association with all patients' poor progression-free survival and overall survival in a univariate analysis, but there was no significantly association with high VEGFA expression and prognosis. Co-expression of PD-L1 and VEGFA exhibited a worst overall survival compared to negative groups (P = 0.005). Conclusions: These findings indicate that high PD-L1 expression could impact both poor overall survival and progression-free survival in patients with resected LADC. Co-expression of PD-L1 and VEGFA may be considered as an important prognostic factor for patients with resected lung adenocarcinoma.

SUBMITTER: Liu S

PROVIDER: S-EPMC6443993 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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PD-L1 Expression Is Associated With VEGFA and LADC Patients' Survival.

Liu Shaochuan S Qin Tingting T Jia Yanan Y Li Kai K

Frontiers in oncology 20190326

Objectives: To elucidate the relationship between VEGFA and PD-L1 expression in lung adenocarcinoma (LADC). Methods: PD-L1 and VEGFA expression were determined by immunohistochemistry with H-score on formalin-fixed paraffin-embedded resected LADC specimens of 129 cases. Results: High PD-L1 expression in 53 (41.1%) patients, high VEGFA expression in 65 (50.4%), and co-expression in 18 (14.0%) were observed. Inverse correlation between expression of PD-L1 and VEGFA was found ( ...[more]

PMID: 30972298

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Project description:Background: Lung cancer treatment has become increasingly dependent upon invasive biopsies to profile tumors for personalized therapy. Recently, tumor expression of programmed death-ligand 1 (PD-L1) has gained interest as a potential predictor of response to immunotherapy. Circulating biomarkers present an opportunity for tumor profiling without the risks of invasive procedures. We characterized PD-L1 expression within populations of nucleated cells in the peripheral blood of lung cancer patients in hopes of expanding the role of liquid biopsy in this setting.Methods: Peripheral blood samples from a multi-institutional prospective study of patients with clinical diagnosis of lung cancer were subjected to cytomorphometric and immunohistochemical evaluation using single-cell, automated slide-based, digital pathology. PD-L1 expression was determined by immunofluorescence.Results: PD-L1 expression was detected within peripheral circulating cells associated with malignancy (CCAM) in 26 of 112 (23%) non-small cell lung cancer patients. Two distinct populations of nucleated, nonhematolymphoid, PD-L1-expressing cells were identified; cytokeratin positive (CK+, PD-L1+, CD45-) and cytokeratin negative (CK-, PD-L1+, CD45-) cells, both with cytomorphometric features (size, nuclear-to-cytoplasm ratio) consistent with tumor cells. Patients with >1.1 PD-L1(+) cell/mL (n = 14/112) experienced worse overall survival than patients with ≤1.1 PD-L1(+) cell/mL (2-year OS: 31.2% vs. 78.8%, P = 0.00159). In a Cox model adjusting for stage, high PD-L1(+) cell burden remained a significant predictor of mortality (HR = 3.85; 95% confidence interval, 1.64-9.09; P = 0.002).Conclusions: PD-L1 expression is detectable in two distinct cell populations in the peripheral blood of lung cancer patients and is associated with worse survival.Impact: These findings could represent a step forward in the development of minimally invasive liquid biopsies for the profiling of tumors. Cancer Epidemiol Biomarkers Prev; 26(7); 1139-45. ©2017 AACR.

Project description:Programmed death ligand 1 (PD-L1) expression is a predictive biomarker of the success of PD-1/PD-L1 inhibitor therapy for patients with advanced non-small cell lung cancer (NSCLC) but its role as a prognostic marker for early-stage resectable NSCLC remains unclear. We studied gene expression levels of immune-related genes PD-1, PD-L1, PD-L2, IDO-1, IDO-2 and INFγ in tumor tissue of surgically resected NSCLC and correlated the finding with clinicopathological features and patient outcomes. A total of 191 consecutive early-stage NSCLC patients who underwent curative pulmonary resection were studied. The mRNA expression levels of immune-related genes were evaluated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) using RT2 Profiler PCR Arrays (Qiagen). PD-1, PD-L2 and IDO-2 gene expression levels were significantly higher in patients with squamous histology (p = 0.001, p = 0.021 and p < 0.001; respectively). PD-1, PD-L1 and IDO-2 gene expression levels were significantly higher in patients with higher stage (p = 0.005, p = 0.048 and p = 0.002, respectively). The univariate analysis for recurrence-free survival (RFS) and overall survival (OS) showed that patients with higher levels of three-genes (PD-L1/PD-L2/INFγ) (hazard ratio (HR)) 1.90 (95% confidence interval (CI), 1.13-3.21), p = 0.015) were associated with a worse RFS, while patients with higher levels of both genes (PD-L1/IDO-2) or (PD-L2/IDO-1) were associated with a worse OS (HR 1.63 95% CI, 1.06-2.51, p = 0.024; HR 1.54 95% CI, 1.02-2.33, p = 0.04; respectively). The multivariate interaction model adjusted for histology and stage confirmed that higher levels of three genes (PD-L1/PD-L2/INFγ) were significantly associated with worse RFS (HR 1.98, p = 0.031) and higher levels of both genes (PD-L1/IDO-2) and (PD-L2/IDO-1) with worse OS (HR 1.98, p = 0.042, HR 1.92, p = 0.022). PD-L1/IDO-2 and PD-L2/IDO-1 co-expression high levels are independent negative prognostic factors for survival in early NSCLC. These features may have important implications for future immune-checkpoint therapeutic approaches.

Dataset Information

PD-L1 Expression Is Associated With VEGFA and LADC Patients' Survival.

Publications

PD-L1 Expression Is Associated With VEGFA and LADC Patients' Survival.

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