Dataset Information

Immune cell infiltration as a biomarker for the diagnosis and prognosis of digestive system cancer.

ABSTRACT: The digestive system cancers are aggressive cancers with the highest mortality worldwide. In this study, we undertook a systematic investigation of the tumor immune microenvironment to identify diagnostic and prognostic biomarkers. The fraction of 22 immune cell types of patients were estimated using CIBERSORT. The least absolute shrinkage and selection operator (LASSO) analysis was carried out to identify important immune predictors. By comparing immune cell compositions in 801 tumor samples and 46 normal samples, we constructed the diagnostic immune score (DIS), showing high specificity and sensitivity in the training (area under the receiver operating characteristic curve [AUC] = 0.929), validation (AUC = 0.935), and different cancer type cohorts (AUC > 0.70 for all). We also established the prognostic immune score (PIS), which was an effective prognostic factor for relapse-free survival in training, validation, and entire cohorts (P < .05). In addition, PIS provided a higher net benefit than TNM stage. A composite nomogram was built based on PIS and patients' clinical information with well-fitted calibration curves (c-index = 0.84). We further used other cohorts from Gene Expression Omnibus databases and obtained similar results, confirming the reliability and validity of the DIS and PIS. In addition, the unsupervised clustering analysis using immune cell proportions revealed 6 immune subtypes, suggesting that the immune types defined as having relatively high levels of M0 or/and M1 macrophages were the high-risk subtypes of relapse. In conclusion, this study comprehensively analyzed the tumor immune microenvironment and identified DIS and PIS for digestive system cancers.

SUBMITTER: Yang S

PROVIDER: S-EPMC6890448 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Immune cell infiltration as a biomarker for the diagnosis and prognosis of digestive system cancer.

Yang Sheng S Liu Tong T Cheng Yanping Y Bai Yunfei Y Liang Geyu G

Cancer science 20191102 12

The digestive system cancers are aggressive cancers with the highest mortality worldwide. In this study, we undertook a systematic investigation of the tumor immune microenvironment to identify diagnostic and prognostic biomarkers. The fraction of 22 immune cell types of patients were estimated using CIBERSORT. The least absolute shrinkage and selection operator (LASSO) analysis was carried out to identify important immune predictors. By comparing immune cell compositions in 801 tumor samples an ...[more]

PMID: 31605436

Similar Datasets

Project description:BackgroundThe SET and MYND domain-containing (SMYD) gene family comprises a set of genes encoding lysine methyltransferases. This study aimed to clarify the relationship between the expression levels of SMYD family members and the prognosis and immune infiltration of malignant tumors of the digestive system.MethodsThe Oncomine, Ualcan, Kaplan-Meier Plotter, cBioPortal, Metascape, and TIMER databases and tools were used to analyze the correlation of SMYD family mRNA expression, clinical stage, TP53 mutation status, prognostic value, gene mutation, and immune infiltration in patients with esophageal carcinoma (ESCA), liver hepatocellular carcinoma (LIHC), and stomach adenocarcinoma (STAD).ResultsIn ESCA, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/3 with the clinical stage, that of SMYD2/3/4/5 with TP53 mutation status, that of SMYD2/4/5 with overall survival (OS), and that of SMYD1/2/3/4 with relapse-free survival (RFS). In LIHC, the mRNA expression of SMYD1/2/3/4/5 was significantly correlated with the incidence rate, that of SMYD2/4/5 with the clinical stage, that of SMYD3/5 with TP53 mutation status, that of SMYD2/3/4/5 with OS, and that of SMYD3/5 with RFS. In STAD, the mRNA expression of SMYD2/3/4/5 was significantly correlated with the incidence rate, that of SMYD1/4 with the clinical stage, that of SMYD1/2/3/5 with TP53 mutation status, that of SMYD1/3/4 with OS, and that of SMYD1/3 with RFS. Furthermore, the function of SMYD family mutation-related genes in ESCA, LIHC, and STAD patients was mainly related to pathways, such as mitochondrial gene expression, mitochondrial matrix, and mitochondrial translation. The expression of SMYD family genes was significantly correlated with the infiltration of six immune cell types and eight types of immune check sites.ConclusionSMYD family genes are differentially expressed and frequently mutated in malignant tumors of the digestive system (ESCA, LIHC, and gastric cancer). They are potential markers for prognostic prediction and have important significance in immunity and targeted therapy.

Project description:Background: Annexin A2 (ANXA2) belongs to the Annexin A family and plays a role in epithelial-mesenchymal transition, fibrinolysis, and other physiological processes. Annexin A2 has been extensively implicated in tumorigenesis and development in previous studies, but its precise role in pan-cancer remains largely unknown. Methods: We adopted bioinformatics methods to explore the oncogenic role of Annexin A2 using different databases, including the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx) biobank, the Human Protein Atlas (HPA), the Gene Expression Profiling Interaction Analysis (GEPIA) and cBioPortal. We analyzed the differential expression of Annexin A2 in different tumors and its relationship with cancer prognosis, immune cell infiltration, DNA methylation, tumor mutation burden (TMB), microsatellite instability (MSI) and mismatch repair (MMR). Furtherly, we conducted a Gene Set Enrichment Analysis (GSEA) to identify the Annexin A2-related pathways. Results: Annexin A2 expression was upregulated in most cancers, except in kidney chromophobe (KICH) and prostate adenocarcinoma (PRAD). Annexin A2 showed a good diagnostic efficacy in twelve types of cancer. The high expression of Annexin A2 was significantly associated with a reduced overall survival, disease-specific survival and progression-free interval in seven cancers. The Annexin A2 expression was variably associated with infiltration of 24 types of immune cells in 32 tumor microenvironments. In addition, Annexin A2 expression was differently associated with 47 immune checkpoints, immunoregulators, DNA methylation, tumor mutation burden, microsatellite instability and mismatch repair in pan-cancer. Gene Set Enrichment Analysis revealed that Annexin A2 was significantly correlated with immune-related pathways in fifteen cancers. Conclusion: Annexin A2 widely correlates with immune infiltration and may function as a promising prognostic biomarker in many tumors, showing its potential as a target for immunotherapy in pan-cancer.

Dataset Information

Immune cell infiltration as a biomarker for the diagnosis and prognosis of digestive system cancer.

Publications

Immune cell infiltration as a biomarker for the diagnosis and prognosis of digestive system cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets