Dataset Information

Prognostic value of CD8?+?PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer.

ABSTRACT: The role of programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) in triple negative breast cancer (TNBC) remains to be fully understood. In this study, we investigated the role of PD-1 as a prognostic marker for TNBC in an Asian cohort (n?=?269). Samples from patients with TNBC were labeled with antibodies against PD-L1 and PD-1, and subjected to NanoString assays to measure the expression of immune-related genes. Associations between disease-free survival (DFS), overall survival (OS) and biomarker expression were investigated. Multivariate analysis showed that tumors with high PD-1+ immune infiltrates harbored significantly increased DFS, and this increase was significant even after controlling for clinicopathological parameters (HR 0.95; P?=?0.030). In addition, the density of cells expressing both CD8 and PD-1, but not the density of CD8-PD-1+ immune infiltrates, was associated with improved DFS. Notably, this prognostic significance was independent of clinicopathological parameters and the densities of total CD8+ cell (HR 0.43, P?=?0.011). At the transcriptional level, high expression of PDCD1 within the tumor was significantly associated with improved DFS (HR 0.38; P?=?0.027). In line with these findings, high expression of IFNG (HR 0.38; P?=?0.001) and IFN signaling genes (HR 0.46; p?=?0.027) was also associated with favorable DFS. Inclusion of PD-1 immune infiltrates and PDCD1 gene expression added significant prognostic value for DFS (?LR?2?=?6.35; P?=?0.041) and OS (?LR?2?=?9.53; P?=?0.008), beyond that provided by classical clinicopathological variables. Thus, PD-1 mRNA and protein expression status represent a promising, independent indicator of prognosis in TNBC.

SUBMITTER: Yeong J

PROVIDER: S-EPMC6366051 | biostudies-other | 2019 Feb

REPOSITORIES: biostudies-other

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Prognostic value of CD8 + PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer.

Yeong Joe J Lim Jeffrey Chun Tatt JCT Lee Bernett B Li Huihua H Ong Clara Chong Hui CCH Thike Aye Aye AA Yeap Wei Hseun WH Yang Yi Y Lim Ansel Yi Herh AYH Tay Timothy Kwang Yong TKY Liu Jin J Wong Siew-Cheng SC Chen Jinmiao J Lim Elaine Hsuen EH Iqbal Jabed J Dent Rebecca R Newell Evan W EW Tan Puay Hoon PH

Journal for immunotherapy of cancer 20190206 1

The role of programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) in triple negative breast cancer (TNBC) remains to be fully understood. In this study, we investigated the role of PD-1 as a prognostic marker for TNBC in an Asian cohort (n = 269). Samples from patients with TNBC were labeled with antibodies against PD-L1 and PD-1, and subjected to NanoString assays to measure the expression of immune-related genes. Associations between disease-free survival (DFS), overall ...[more]

PMID: 30728081

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Project description:BACKGROUND:Sphingosine-1-phosphate receptor (S1PR1) is involved in vascular development, a key process in tumorigenesis. This study aimed to evaluate its roles in tumor development and prognosis. METHODS:S1PR1 expression levels were analyzed using TIMER and Oncomine database, and the prognostic significance of S1PR1 was assessed using PrognoScan and Kaplan-Meier plotter databases. The relationship between S1PR1 and tumor-infiltrated immune cells was analyzed using TIMER. RESULTS:S1PR1 expression was remarkably lower in breast and lung cancer tissues than in the corresponding normal tissues. Lower expression was related to poor overall survival and disease-free survival in breast invasive carcinoma (BRCA), lung adenocarcinoma (LUAD), and lung squamous cell carcinoma (LUSC). A functional network analysis confirmed the function of S1PR1 in regulating vasculogenesis. In addition, S1PR1 levels were significantly negative with regard to the tumor purity of BRCA (r?=?-?0.508, P?= 1.76e-66), LUAD (r?=?-?0.353, P?= 6.05e-16), and LUSC (r?=?-?0.402, P?=?-?5.20e-20). Furthermore, S1PR1 levels were significantly positive with regard to infiltrating CD8+ (r?=?0.38, P?= 5.91e-35) and CD4+ T cells (r?=?0.335, P?= 1.03e-26), macrophages (r?=?0.219, P?= 3.67e-12), neutrophils (r?=?0.168, P?= 2.03e-7), and dendritic cells (DCs) (r?=?0.208, P?= 9.14e-11) in BRCA; S1PR1 levels were significantly positive with regard to CD8+ T cells (r?=?0.308, P?= 3.61e-12), macrophages (r?=?0.376, P?= 1.01e-17), neutrophils (r?=?0.246, P?= 4.15e-8), and DCs (r?=?0.207, P?= 4.16e-6) in LUAD; and positive with regard to B cells (r?=?0.356, P?= 1.57e-15), CD8+ (r?=?0.459, P?= 3.83e-26) and CD4+ T cells (r?=?0.338, P?= 3.98e-14), macrophages (r?=?0.566, P?= 2.61e-45), neutrophils (r?=?0.453, P?= 1.79e-25), and DCs (r?=?0.56, P?= 2.12e-40) in LUSC. CONCLUSIONS:S1PR1 levels are positively correlated with multiple immune markers in breast and lung cancer. These observed correlations between S1PR1 and the prognosis and immune cell infiltration provide a foundation for further research on its immunomodulatory role in cancer.

Dataset Information

Prognostic value of CD8?+?PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer.

Publications

Prognostic value of CD8 + PD-1+ immune infiltrates and PDCD1 gene expression in triple negative breast cancer.

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