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Prognostic genes in the tumor microenvironment in cervical squamous cell carcinoma.

ABSTRACT: Cervical squamous cell carcinoma (CSCC) is one of the most commonly occurring gynecological malignancies. Because CSCC is a biologically heterogeneous disease, its prognosis varies. Therefore, identifying prognostic biomarkers that reflect its biological heterogeneity could lead to better interventions for patients with a poor prognosis. This study used the ESTIMATE algorithm to identify immune related prognostic genes within the tumor microenvironment of CSCC. The results revealed that high immune scores were associated with better overall survival (P = 0.029). Differential expression analysis revealed 384 intersection genes influencing both the immune and stromal scores. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses showed the 384 intersection genes to be mainly enriched for T cell activation, the region of the membrane, carbohydrate binding, and cytokine-cytokine receptor interaction. Among them, 149 immune genes were predictive of overall survival in CSCC. These findings provide a more comprehensive understanding of immune genes within the tumor microenvironment as well as a list of immune genes prognostic in CSCC.

SUBMITTER: Pan XB

PROVIDER: S-EPMC6914434 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Prognostic genes in the tumor microenvironment in cervical squamous cell carcinoma.

Pan Xin-Bin XB Lu Yan Y Huang Jian-Li JL Long Ying Y Yao De-Sheng DS

Aging 20191118 22

Cervical squamous cell carcinoma (CSCC) is one of the most commonly occurring gynecological malignancies. Because CSCC is a biologically heterogeneous disease, its prognosis varies. Therefore, identifying prognostic biomarkers that reflect its biological heterogeneity could lead to better interventions for patients with a poor prognosis. This study used the ESTIMATE algorithm to identify immune related prognostic genes within the tumor microenvironment of CSCC. The results revealed that high imm ...[more]

PMID: 31740624

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Project description:Background Esophageal cancer (EC) is a highly aggressive malignancy that is classified as esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC). Infiltrating stromal/immune cells, a major component of the tumor immune microenvironment (TIME), have prognostic significance in various cancers. Methods In this study we investigated genes and immune factors in the tumor microenvironment (TME) of ESCC and EAC that can serve as prognostic biomarkers. Stromal and immune scores were calculated using the Estimation of Stromal and Immune Cells in Malignant Tumor Tissues Using Expression Data (ESTIMATE) algorithm based on gene expression profiles of patient-derived tumor tissues in The Cancer Genome Atlas database. The correlation between ESTIMATE scores and survival rates in EC were analyzed. A comparison of high and low stromal/immune score groups revealed multiple differentially expressed genes (DEGs) as candidate prognostic genes; their role in immune-related biological processes was evaluated by functional and protein-protein interaction (PPI) network analyses, and the genes were validated using Gene Expression Omnibus datasets. Additionally, 22 tumor-infiltrating immune cell (TIIC) subsets were analyzed using the CIBERSORT algorithm. Results Median stromal score was higher whereas immune score was lower in ESCC than in EAC (both P<0.01). Stromal score was lower in female as compared to male ESCC patients (P<0.05), and was significantly correlated with T stage (P<0.05). In EAC, median immune score was higher in female as compared to male patients (P<0.05) and was correlated with tumor-node-metastasis stage (P<0.05). The identified DEGs were mainly involved in lymphocyte (especially T-lymphocyte) activation and carbohydrate binding. Moreover, the levels of infiltrating resting-stage dendritic cells, CD8+ T cells, naïve B cells, activated mast cells, and resting memory CD4+ T cells were significantly correlated with EC prognosis (P<0.05). Conclusions The immune microenvironment of ESCC and EAC are quite different. We have found genes with prognostic value in multiple tumor databases.

Project description:The host's immune system plays a pivotal role in many tumor types, including squamous cell carcinomas (SCCs). We aim to identify immunological prognosticators for lymph node metastases (LNM) and disease-specific survival (DSS) in penile SCC. For this retrospective observational cohort study, penile SCC patients (n?=?213) treated in the Netherlands Cancer Institute, were selected if sufficient formalin-fixed, paraffin-embedded tumor material was available. Analysis included previously described high-risk human papilloma virus (hrHPV) status, immunohistochemical scores for classical and non-classical human leukocyte antigen (HLA) class I, programmed death ligand-1 (PD-L1) expression, and novel data on tumor-infiltrating macrophages and cytotoxic an regulatory T-cells. Clinicopathological characteristics and extended follow-up were also included. Regression analyses investigated relationships of the immune parameters with LNM and DSS. In the total cohort, diffuse PD-L1 tumor-cell expression, CD163+ macrophage infiltration, non-classical HLA class I upregulation, and low stromal CD8+ T-cell infiltration were all associated with LNM. In the multivariable model, only tumor PD-L1 expression remained a significant predictor for LNM (odds ratio (OR) 2.8, p?=?0.05). hrHPV negativity and diffuse PD-L1 tumor-cell expression were significantly associated with poor DSS and remained so upon correction for clinical parameters [hazard ratio (HR) 9.7, p?<?0.01 and HR 2.8, p?=?0.03]. The only immune factor with different expression in HPV+ and HPV- tumors was PD-L1, with higher PD-L1 expression in the latter (p?=?0.03). In the HPV- cohort (n?=?158), LNM were associated with diffuse PD-L1 tumor-cell expression, high intratumoral CD163+ macrophage infiltration, and low number of stromal CD8+ T-cells. The first two parameters were also linked to DSS. In the multivariable regression model, diffuse PD-L1 expression remained significantly unfavorable for DSS (HR 5.0, p?<?0.01). These results emphasize the complexity of the tumor microenvironment in penile cancer and point toward several possible immunotherapy targets. Here described immune factors can aid risk-stratification and should be evaluated in clinical immunotherapy studies to ultimately lead to patient tailored treatment.

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Prognostic genes in the tumor microenvironment in cervical squamous cell carcinoma.

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Prognostic genes in the tumor microenvironment in cervical squamous cell carcinoma.

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