Dataset Information

HTRA3 Is a Prognostic Biomarker and Associated With Immune Infiltrates in Gastric Cancer

ABSTRACT: HtrA serine peptidase 3 (HTRA3) participates in multiple signal pathways and plays an important regulatory role in various malignancies; however, its role on prognosis and immune infiltrates in gastric cancer (GC) remains unclear. The study investigated HTRA3 expression in tumor tissues and its association with immune infiltrates, and determined its prognostic roles in GC patients. Patients with GC were collected from the cancer genome atlas (TCGA). We compared the expression of HTRA3 in GC and normal gastric mucosa tissues with Wilcoxon rank sum test. And logistic regression was used to evaluate the relationship between HTRA3 and clinicopathological characters. Gene ontology (GO) term analysis, Gene set enrichment analysis (GSEA), and single-sample Gene Set Enrichment Analysis (ssGSEA) was conducted to explain the enrichmental pathways and functions and quantify the extent of immune cells infiltration for HTRA3. Kaplan-Meier analysis and Cox regression were performed to evaluate the correlation between HTRA3 and survival rates. A nomogram, based on Cox multivariate analysis, was used to predict the impact of HTRA3 on prognosis. High HTRA3 expression was significantly correlated with tumor histological type, histological grade, clinical stage, T stage, and TP53 status (P < 0.05). HTRA3-high GC patients had a lower 10-year progression-free interval [PFI; hazard ratio (HR): 1.46; 95% confidence interval (CI): 1.02–2.08; P = 0.038], disease-specific survival (DSS; HR: 1.65; CI: 1.08–2.52; P = 0.021) and overall survival (OS; HR: 1.59; CI: 1.14–2.22; P = 0.006). Multivariate survival analysis showed that HTRA3 was an independent prognostic marker for PFI (HR: 1.456; CI: 1.021–2.078; P = 0.038), DSS (HR: 1.650; CI: 1.079–2.522; P = 0.021) and OS [hazard ratio (HR): 1.590; 95% confidence interval (CI):1.140–2.219; P = 0.006]. The C-indexes and calibration plots of the nomogram based on multivariate analysis indicated an effective predictive performance for GC patients. GSEA showed that High HTRA3 expression may activate NF-?B pathway, YAP1/WWTR1/TAZ pathway, and TGF? pathway. There was a negative correlation between the HTRA3 expression and the abundances of adaptive immunocytes (T helper cell 17 cells) and a positive correlation with abundances of innate immunocytes (natural killer cells, macrophages etc.). HTRA3 plays a vital role in GC progression and prognosis and could be a moderate biomarker for prediction for survival after gastrectomy.

SUBMITTER: Ji C

PROVIDER: S-EPMC7786138 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BackgroundGastric cancer (GC) is the most prevalent malignancy among the digestive system tumors. Increasing evidence has revealed that lower mRNA expression of ANXA9 is associated with a poor prognosis in colorectal cancer. However, the role of ANXA9 in GC remains largely unknown.Material and methodsThe Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas databases were used to investigate the expression of ANXA9 in GC, which was then validated in the four Gene Expression Omnibus (GEO) datasets. The diagnostic value of ANXA9 for GC patients was demonstrated using a receiver operating characteristic (ROC) curve. The correlation between ANXA9 expression and clinicopathological parameters was analyzed in The Cancer Genome Atlas (TCGA) and UALCAN databases. The Kaplan-Meier (K-M) survival curve was used to elucidate the relationship between ANXA9 expression and the survival time of GC patients. We then performed a gene set enrichment analysis (GSEA) to explore the biological functions of ANXA9. The relationship of ANXA9 expression and cancer immune infiltrates was analyzed using the Tumor Immune Estimation Resource (TIMER). In addition, the potential mechanism of ANXA9 in GC was investigated by analyzing its related genes.ResultsANXA9 was significantly up-regulated in GC tissues and showed obvious diagnostic value. The expression of ANXA9 was related to the age, gender, grade, TP53 mutation, and histological subtype of GC patients. We also found that ANXA9 expression was associated with immune-related biological function. ANXA9 expression was also correlated with the infiltration level of CD8+ T cells, neutrophils, and dendritic cells in GC. Additionally, copy number variation (VNV) of ANXA9 occurred in GC patients. Function enrichment analyses revealed that ANXA9 plays a role in the GC progression by interacting with its related genes.ConclusionsOur results provide strong evidence of ANXA9 expression as a prognostic indicator related to immune responses in GC.

Project description:Background The prognosis is poor for hepatocellular carcinoma (HCC), a tumor and cancer associated with inflammation that is common. New data showed that significant levels of KIAA1522 were expressed in HCC tissues and cell lines, suggesting that KIAA1522 may be a highly useful prognostic marker for HCC. However, its biochemical processes and impacts on the immune system go deeper. Objective To verify the significance of KIAA1522 in HCC and investigate its related carcinogenic mechanisms. Methods Studies examining the relationship between KIAA1522 expression and clinical-pathologic characteristics in HCC have been checked in the Cancer Genome Atlas (TCGA) database. A receiver operating characteristic (ROC) curve was used to assess the diagnostic efficacy of KIAA1522 in HCC. Western blot analysis was used to find the presence of the KIAA1522 protein in the tumor and paraneoplastic tissues of eight randomly chosen HCC patients. The GSVA program in R language was used to evaluate the relationship between KIAA1522 and immune cell infiltration in HCC. We searched the Search Tool for the Retrieval of Interacting Genes (STRING) database for interacting proteins connected to the expression of KIAA1522. Pathways were involved in the enrichment analysis of KIAA1522 to anticipate potential mechanisms through which KIAA1522 may affect immunological infiltration. Results Our study found that KIAA1522 was commonly elevated in HCC tumor tissues and that it also signaled a bad outcome. We found an inverse link between KIAA1522 and cytotoxic cells and an inverse relationship between KIAA1522 and Th2 cell infiltration. In STRING analysis, the top 5 coexpressed proteins of KIAA1522 were BAIAP2, NCK2, TSNAXIP1, POGK, and KLHL31. The effect of KIAA1522 on HCC may entail cell cycle alteration, an immunological response, and suppression of the PPAR signaling pathway. Conclusion High expression of KIAA1522 was linked to HCC immune cell infiltration, disease progression, and a poor prognosis.

Project description:Background: Layilin (LAYN) is a critical gene that regulates T cell function. However, the correlations of LAYN to prognosis and tumor-infiltrating lymphocytes in different cancers remain unclear. Methods: LAYN expression was analyzed via the Oncomine database and Tumor Immune Estimation Resource (TIMER) site. We evaluated the influence of LAYN on clinical prognosis using Kaplan-Meier plotter, the PrognoScan database and Gene Expression Profiling Interactive Analysis (GEPIA). The correlations between LAYN and cancer immune infiltrates was investigated via TIMER. In addition, correlations between LAYN expression and gene marker sets of immune infiltrates were analyzed by TIMER and GEPIA. Results: A cohort (GSE17536) of colorectal cancer patients showed that high LAYN expression was associated with poorer overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS). In addition, high LAYN expression was significantly correlated with poor OS and progression-free survival (PFS) in gastric cancers (OS HR = 1.97, P = 3.6e-10; PFS HR = 2.12, P = 2.3e-10). Moreover, LAYN significantly impacts the prognosis of diverse cancers via The Cancer Genome Atlas (TCGA). Specifically, high LAYN expression was correlated with worse OS and PFS in stage 2 to 4 but not stage 1 and stage N0 gastric cancer patients (P = 0.28, 0.34; P = 0.073, 0.092). LAYN expression was positively correlated with infiltrating levels of CD4+ T and CD8+ T cells, macrophages, neutrophils, and dendritic cells (DCs) in colon adenocarcinoma (COAD) and stomach adenocarcinoma (STAD). LAYN expression showed strong correlations with diverse immune marker sets in COAD and STAD. Conclusions: These findings suggest that LAYN is correlated with prognosis and immune infiltrating levels of, including those of CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and DCs in multiple cancers, especially in colon and gastric cancer patients. In addition, LAYN expression potentially contributes to regulation of tumor-associated macrophages (TAMs), DCs, T cell exhaustion and Tregs in colon and gastric cancer. These findings suggest that LAYN can be used as a prognostic biomarker for determining prognosis and immune infiltration in gastric and colon cancers.

Dataset Information

HTRA3 Is a Prognostic Biomarker and Associated With Immune Infiltrates in Gastric Cancer

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets