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-κB pathway, YAP1/WWTR1/TAZ pathway, and TGFβ 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.

Integrative Single-Cell RNA-Seq and ATAC-Seq Analysis of Mesenchymal Stem/Stromal Cells Derived from Human Placenta

“…For example, CCL2, PRDM1, and LY6E were specifically highly expressed in immunomodulation1, and HTRA3 and PTGES were solely expressed in immunomodulation2 ( Figure 1F ). All these genes are involved in different immunomodulating processes based on previous studies ( Rafei et al, 2008 ; Fu et al, 2017 ; Wang T. et al, 2020 ; Ji et al, 2020 ; Pfaender et al, 2020 ) ( Figure 1E ). In line with this, we also observed overlapped features of immunomodulation and extracellular matrix-related GO terms in the two clusters, which are important for the maintenance of MSC functions ( Figure 1G ).…”

CHSY3 As A Potential Therapeutic Target For Gastric Cancer

“…Early diagnosis of cancer is the key to improving the overall survival rate of patients, reducing disease-free progression, and reducing the risk of recurrence. Therefore, there is an urgent need to determine reliable predictive biomarkers and new therapeutic targets to truly improve the prognosis of patients.Studies have shown that abnormal gene expression is closely related to the occurrence and development of cancer [22,23].Nan Zhou's research shows that HTRA3 is abnormally highly expressed in gastric cancer tissues, and the high expression of HTRA3 indicates a poor prognosis [24].Liya Hu's research found that PDPN is a prognostic biomarker of gastric cancer and is related to immune in ltration [25].Li Rong's research con rmed that COL1A2 is a prognostic biomarker of gastric cancer through bioinformatics and Meta-analysis, which can improve the clinical predictive ability of gastric cancer [26].Therefore, it is very necessary to carry out bioinformatics research on gastric cancer. CHSY3 (Chondroitin Sulfate Synthase 3) is a Protein Coding gene,An important paralog of this gene is CHSY1.At present, the research on CHSY3 bioinformatics is relatively scarce.In our research, we mainly focus on the role of CHSY3 in gastric cancer.…”

Carvacrol suppressed LIHC via SLC6A3

“…We calculated the survival association of these target genes because we wanted to obtain potential targets that affect survival. So far, TCGA data were widely used in prognostic studies [40][41][42]. The potential association of gene expression and overall survival might identify a biomarker for cancer prognosis or functional cancer regulator for cancer.…”