Cargando…

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

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 asso...

Descripción completa

Detalles Bibliográficos
Autores principales: Ji, Ce, Sun, Li-Sha, Xing, Fei, Niu, Nan, Gao, Hong-Li, Dai, Jing-Wei, Zhou, Nan, Jiang, Ben-Chun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786138/
https://www.ncbi.nlm.nih.gov/pubmed/33425760
http://dx.doi.org/10.3389/fonc.2020.603480
_version_ 1783632567547723776
author Ji, Ce
Sun, Li-Sha
Xing, Fei
Niu, Nan
Gao, Hong-Li
Dai, Jing-Wei
Zhou, Nan
Jiang, Ben-Chun
author_facet Ji, Ce
Sun, Li-Sha
Xing, Fei
Niu, Nan
Gao, Hong-Li
Dai, Jing-Wei
Zhou, Nan
Jiang, Ben-Chun
author_sort Ji, Ce
collection PubMed
description 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.
format Online
Article
Text
id pubmed-7786138
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-77861382021-01-07 HTRA3 Is a Prognostic Biomarker and Associated With Immune Infiltrates in Gastric Cancer Ji, Ce Sun, Li-Sha Xing, Fei Niu, Nan Gao, Hong-Li Dai, Jing-Wei Zhou, Nan Jiang, Ben-Chun Front Oncol Oncology 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. Frontiers Media S.A. 2020-12-23 /pmc/articles/PMC7786138/ /pubmed/33425760 http://dx.doi.org/10.3389/fonc.2020.603480 Text en Copyright © 2020 Ji, Sun, Xing, Niu, Gao, Dai, Zhou and Jiang http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Ji, Ce
Sun, Li-Sha
Xing, Fei
Niu, Nan
Gao, Hong-Li
Dai, Jing-Wei
Zhou, Nan
Jiang, Ben-Chun
HTRA3 Is a Prognostic Biomarker and Associated With Immune Infiltrates in Gastric Cancer
title HTRA3 Is a Prognostic Biomarker and Associated With Immune Infiltrates in Gastric Cancer
title_full HTRA3 Is a Prognostic Biomarker and Associated With Immune Infiltrates in Gastric Cancer
title_fullStr HTRA3 Is a Prognostic Biomarker and Associated With Immune Infiltrates in Gastric Cancer
title_full_unstemmed HTRA3 Is a Prognostic Biomarker and Associated With Immune Infiltrates in Gastric Cancer
title_short HTRA3 Is a Prognostic Biomarker and Associated With Immune Infiltrates in Gastric Cancer
title_sort htra3 is a prognostic biomarker and associated with immune infiltrates in gastric cancer
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786138/
https://www.ncbi.nlm.nih.gov/pubmed/33425760
http://dx.doi.org/10.3389/fonc.2020.603480
work_keys_str_mv AT jice htra3isaprognosticbiomarkerandassociatedwithimmuneinfiltratesingastriccancer
AT sunlisha htra3isaprognosticbiomarkerandassociatedwithimmuneinfiltratesingastriccancer
AT xingfei htra3isaprognosticbiomarkerandassociatedwithimmuneinfiltratesingastriccancer
AT niunan htra3isaprognosticbiomarkerandassociatedwithimmuneinfiltratesingastriccancer
AT gaohongli htra3isaprognosticbiomarkerandassociatedwithimmuneinfiltratesingastriccancer
AT daijingwei htra3isaprognosticbiomarkerandassociatedwithimmuneinfiltratesingastriccancer
AT zhounan htra3isaprognosticbiomarkerandassociatedwithimmuneinfiltratesingastriccancer
AT jiangbenchun htra3isaprognosticbiomarkerandassociatedwithimmuneinfiltratesingastriccancer