Dataset Information

Tumour infiltrating lymphocytes and immune-related genes as predictors of outcome in pancreatic adenocarcinoma.

ABSTRACT:

Background

We investigated the correlation between pancreatic ductal adenocarcinoma patient prognosis and the presence of tumour infiltrating lymphocytes and expression of 521 immune system genes.

Methods

Intratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochemistry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenectomy. The results were correlated with gene expression profile using the digital multiplexed NanoString nCounter analysis system (NanoString Technologies, Seattle, WA, USA).

Results

Twenty immune system genes were significantly differentially expressed in patients with a good prognosis relative to patients with a worse prognosis: TLR2 and TLR7 (Toll-like receptor superfamily); CD4, CD37, FOXP3, PTPRC (B cell and T cell signalling); IRF5, IRF8, STAT1, TFE3 (transcription factors); ANP32B, CCND3 (cell cycle); BTK (B cell development); TNF, TNFRF1A (TNF superfamily); HCK (leukocyte function); C1QA (complement system); BAX, PNMA1 (apoptosis); IKBKE (NFκB pathway). Differential expression was more than twice log 2 for TLR7, TNF, C1QA, FOXP3, and CD37.

Discussion

Tumour infiltrating lymphocytes were present at higher levels in samples from patients with better prognosis. Our findings indicate that tumour infiltrating lymphocyte levels and expression level of the immune system genes listed above influence pancreatic ductal adenocarcinoma prognosis. This information could be used to improve selection of best responders to immune inhibitors.

SUBMITTER: D'Angelo A

PROVIDER: S-EPMC6681957 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Publications

Tumour infiltrating lymphocytes and immune-related genes as predictors of outcome in pancreatic adenocarcinoma.

D'Angelo Alberto A Sobhani Navid N Roviello Giandomenico G Bagby Stefan S Bonazza Deborah D Bottin Cristina C Giudici Fabiola F Zanconati Fabrizio F De Manzini Nicolo N Guglielmi Alessandra A Generali Daniele D

PloS one 20190805 8

<h4>Background</h4>We investigated the correlation between pancreatic ductal adenocarcinoma patient prognosis and the presence of tumour infiltrating lymphocytes and expression of 521 immune system genes.<h4>Methods</h4>Intratumoural CD3+, CD8+, and CD20+ lymphocytes were examined by immunohistochemistry in 12 PDAC patients with different outcomes who underwent pancreaticoduodenectomy. The results were correlated with gene expression profile using the digital multiplexed NanoString nCounter anal ...[more]

PMID: 31381571

Similar Datasets

Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) has persisted as one of the worst prognostic tumors with a 5-year survival rate of lower than 6%. Although many studies have investigated PDAC, new biomarkers are required to ensure early diagnosis and predict the prognosis of PDAC.MethodsIn this study, we used bioinformatics methods to evaluate differences in the expression of solute carrier (SLC) family genes in tumors and non-tumors. A Kaplan-Meier analysis, least absolute shrinkage and selection operator (LASSO) analysis, and multivariate Cox proportional hazards regression analysis were used to evaluate the relationship between SLC genes and prognosis using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets. The prognostic signature was constructed depending on the risk score to assess the impact of multiple genes on the prognosis, receiver operating characteristic (ROC) curves and forest plot was constructed to assess the ability to predict the prognosis and effects of clinical variables in both high- and low-risk groups. Tumor-infiltrating immune cells were evaluated using Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) in both high- and low-risk groups.ResultsIn 32 SLC genes, 9 were significantly associated with the OS after LASSO analysis. SLC19A3 (P=0.007), SLC25A39 (P=0.027), SLC39A11 (P=0.043) were significantly associated with prognosis and included into the prognostic model. CIBERSORT demonstrated that memory B cells (P=0.004), naive B cells (P=0.007), CD8 T cells (P=0.003), activated memory CD4 T cells (P=0.004), and activated NK cells (P=0.019) were significantly higher in the low-risk group. Gene set enrichment analysis (GSEA) showed that potential molecular mechanisms enriched in MYC and p53 signaling pathways.ConclusionsSLC19A3, SLC25A35, and SLC39A11 were significantly relative to the prognosis of PDAC and changed the tumor microenvironment, as well as the MYC and p53 signaling pathways. The SLC19A3 gene may represent a new tumor suppressor in PDAC.

Dataset Information

Tumour infiltrating lymphocytes and immune-related genes as predictors of outcome in pancreatic adenocarcinoma.

Background

Methods

Results

Discussion

Publications

Tumour infiltrating lymphocytes and immune-related genes as predictors of outcome in pancreatic adenocarcinoma.

Similar Datasets

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