Dataset Information

Chromogenic Multiplex Immunohistochemistry Reveals Modulation of the Immune Microenvironment Associated with Survival in Elderly Patients with Lung Adenocarcinoma.

ABSTRACT: With underrepresentation of elderly patients with lung adenocarcinoma (LADC) in anti-PD-1/PD-L1 clinical trials, better understanding of the interplay of PD-L1 and tumor-associated immune cells (TAICs) could assist clinicians in stratifying these patients for immunotherapy. One hundred and one patients with LADCs, stratified by age, were included for analysis of PD-L1 expression and density of TAICs expressing CD4, CD8, and CD33, by using multiplex chromogenic immunohistochemistry (IHC) assays and automated digital quantification. The CD4?/CD8? ratio was significantly higher in elderly patients. In patients <75 years, the density of CD4?, CD8?, and PD-L1 in TAICs showed a positive significant correlation with PD-L1 expression in tumor cells (TCs), while a lower correlation was observed in the elderly population. In the latter, a high CD4?/CD8? ratio, and combined PD-L1 expression ?1% TCs with a low CD8? density, low CD33? density, and a high CD4? density correlated to worse overall survival. We identified differences according to age in the CD4?/CD8? ratio and in correlation between PD-L1 expression and the density of TAICs in LADC patients. Distinct groups of tumor microenvironments had an impact on the OS of elderly patients with LADC.

SUBMITTER: Ilie M

PROVIDER: S-EPMC6162494 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Chromogenic Multiplex Immunohistochemistry Reveals Modulation of the Immune Microenvironment Associated with Survival in Elderly Patients with Lung Adenocarcinoma.

Ilié Marius M Beaulande Mélanie M Ben Hadj Saima S Chamorey Emmanuel E Schiappa Renaud R Long-Mira Elodie E Lassalle Sandra S Butori Catherine C Cohen Charlotte C Leroy Sylvie S Guérin Olivier O Mouroux Jérôme J Marquette Charles-Hugo CH Pomerol Jean-François JF Erb Gilles G Hofman Véronique V Hofman Paul P

Cancers 20180913 9

With underrepresentation of elderly patients with lung adenocarcinoma (LADC) in anti-PD-1/PD-L1 clinical trials, better understanding of the interplay of PD-L1 and tumor-associated immune cells (TAICs) could assist clinicians in stratifying these patients for immunotherapy. One hundred and one patients with LADCs, stratified by age, were included for analysis of PD-L1 expression and density of TAICs expressing CD4, CD8, and CD33, by using multiplex chromogenic immunohistochemistry (IHC) assays a ...[more]

PMID: 30216999

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Project description:BackgroundLung adenocarcinoma (LUAD) is the most common histological type of lung cancers, which is the primary cause of cancer-related mortality worldwide. Growing evidence has suggested that tumor microenvironment (TME) plays a pivotal role in tumorigenesis and progression. Hence, we investigate the correlation of TME related genes with LUAD prognosis.MethodThe information of LUAD gene expression data was obtained from The Cancer Genome Atlas (TCGA). According to their immune/stromal scores calculated by the ESTIMATE algorithm, differentially expressed genes (DEGs) were identified. Then, we performed univariate Cox regression analysis on DEGs to obtain genes that are apparently bound up with LUAD survival (SurGenes). Functional annotation and protein-protein interaction (PPI) was also conducted on SurGenes. By validating the SurGenes with data sets of lung cancer from the Gene Expression Omnibus (GEO), 106 TME related SurGenes were generated. Further, intersection analysis was executed between the 106 TME related SurGenes and hub genes from PPI network, PTPRC and CD19 were obtained. Gene Set Enrichment Analysis and CIBERSORT analysis were performed on PTPRC and CD19. Based on the TCGA LUAD dataset, we conducted factor analysis and Step-wise multivariate Cox regression analysis for 106 TME related SurGenes to construct the prognostic model for LUAD survival prediction. The LUAD dataset in GEO (GSE68465) was used as the testing dataset to confirm the prognostic model. Multivariate Cox regression analysis was used between risk score from the prognostic model and clinical parameters.ResultA total of 106 TME related genes were collected in our research totally, which were markedly correlated with the overall survival (OS) of LUAD patient. Bioinformatics analysis suggest them mainly concentrated on immune response, cell adhesion, and extracellular matrix. More importantly, among 106 TME related SurGenes, PTPRC and CD19 were highly interconnected nodes among PPI network and correlated with immune activity, exhibiting significant prognostic potential. The prognostic model was a weighted linear combination of the 106 genes, by which the low-OS LUAD samples could be separated from the high-OS samples with success. This model was also able to rebustly predict the situation of survival (training set: p-value < 0.0001, area under the curve (AUC) = 0.649; testing set: p-value = 0.0009, AUC = 0.617). By combining with clinical parameters, the prognostic model was optimized. The AUC achieved 0.716 for 3 year and 0.699 for 5 year.ConclusionA series of TME-related prognostic genes were acquired in this research, which could reflect immune disorders within TME, and PTPRC and CD19 show the potential to be an indicator for LUAD prognosis and tumor microenvironment modulation. The prognostic model constructed base on those prognostic genes presented a high predictive ability, and may have clinical implications in the overall survival prediction of LUAD.

Dataset Information

Chromogenic Multiplex Immunohistochemistry Reveals Modulation of the Immune Microenvironment Associated with Survival in Elderly Patients with Lung Adenocarcinoma.

Publications

Chromogenic Multiplex Immunohistochemistry Reveals Modulation of the Immune Microenvironment Associated with Survival in Elderly Patients with Lung Adenocarcinoma.

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