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Data mining combines bioinformatics discover immunoinfiltration-related gene SERPINE1 as a biomarker for diagnosis and prognosis of stomach adenocarcinoma
Stomach adenocarcinoma (STAD) is a type of cancer which often at itsadvanced stage apon diagnosis and mortality in clinical practice. Several factors influencethe prognosis of STAD, including the expression and regulation of immune cells in the tumor microenvironment. We here investigated the biomar...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9876925/ https://www.ncbi.nlm.nih.gov/pubmed/36697459 http://dx.doi.org/10.1038/s41598-023-28234-7 |
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author | Zhai, Yiyan Liu, Xinkui Huang, Zhihong Zhang, Jingyuan Stalin, Antony Tan, Yingying Zhang, Fanqin Chen, Meilin Shi, Rui Huang, Jiaqi Wu, Chao Wu, Zhishan Lu, Shan You, Leiming Wu, Jiarui |
author_facet | Zhai, Yiyan Liu, Xinkui Huang, Zhihong Zhang, Jingyuan Stalin, Antony Tan, Yingying Zhang, Fanqin Chen, Meilin Shi, Rui Huang, Jiaqi Wu, Chao Wu, Zhishan Lu, Shan You, Leiming Wu, Jiarui |
author_sort | Zhai, Yiyan |
collection | PubMed |
description | Stomach adenocarcinoma (STAD) is a type of cancer which often at itsadvanced stage apon diagnosis and mortality in clinical practice. Several factors influencethe prognosis of STAD, including the expression and regulation of immune cells in the tumor microenvironment. We here investigated the biomarkers related to the diagnosis and prognosis of gastric cancer, hoping to provide insights for the diagnosis and treatment of gastric cancer in the future. STAD and normal patient RNA sequencing data sets were accessed from the cancer genome atlas (TCGA database). Differential genes were determined and obtained by using the R package DESeq2. The stromal, immune, and ESTIMATE scores are calculated by the ESTIMATE algorithm, followed by the modular genes screening using the R package WGCNA. Subsequently, the intersection between the modular gene and the differential gene was taken and the STRING database was used for PPI network module analysis. The R packages clusterProfiler, enrichplot, and ggplot2 were used for GO and KEGG enrichment analysis. Cox regression analysis was used to screen survival-related genes, and finally, the R package Venn Diagram was used to take the intersection and obtain 7 hub genes. The time-dependent ROC curve and Kaplan–Meier survival curve were used to find the SERPINE1 gene, which plays a critical role in prognosis. Finally, the expression pattern, clinical characteristics, and regulatory mechanism of SERPINE1 were analyzed in STAD. We revealed that the expression of SERPINE1 was significantly increased in the samples from STAD compared with normal samples. Cox regression, time-dependent ROC, and Kaplan–Meier survival analyses demonstrated that SERPINE1 was significantly related to the adverse prognosis of STAD patients. The expression of SERPINE1 increased with the progression of T, N, and M classification of the tumor. In addition, the results of immune infiltration analysis indicated that the immune cells’ expression were higher in high SERPINE1 expression group than that in low SERPINE1 expression group, including CD4(+) T cells, B cells, CD8(+) T cells, macrophages, neutrophils and other immune cells. SERPINE1 was closely related to immune cells in the STAD immune microenvironment and had a synergistic effect with the immune checkpoints PD1 and PD-L1. In conclusion, we proved that SERPINE1 is a promising prognostic and diagnostic biomarker for STAD and a potential target for immunotherapy. |
format | Online Article Text |
id | pubmed-9876925 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98769252023-01-27 Data mining combines bioinformatics discover immunoinfiltration-related gene SERPINE1 as a biomarker for diagnosis and prognosis of stomach adenocarcinoma Zhai, Yiyan Liu, Xinkui Huang, Zhihong Zhang, Jingyuan Stalin, Antony Tan, Yingying Zhang, Fanqin Chen, Meilin Shi, Rui Huang, Jiaqi Wu, Chao Wu, Zhishan Lu, Shan You, Leiming Wu, Jiarui Sci Rep Article Stomach adenocarcinoma (STAD) is a type of cancer which often at itsadvanced stage apon diagnosis and mortality in clinical practice. Several factors influencethe prognosis of STAD, including the expression and regulation of immune cells in the tumor microenvironment. We here investigated the biomarkers related to the diagnosis and prognosis of gastric cancer, hoping to provide insights for the diagnosis and treatment of gastric cancer in the future. STAD and normal patient RNA sequencing data sets were accessed from the cancer genome atlas (TCGA database). Differential genes were determined and obtained by using the R package DESeq2. The stromal, immune, and ESTIMATE scores are calculated by the ESTIMATE algorithm, followed by the modular genes screening using the R package WGCNA. Subsequently, the intersection between the modular gene and the differential gene was taken and the STRING database was used for PPI network module analysis. The R packages clusterProfiler, enrichplot, and ggplot2 were used for GO and KEGG enrichment analysis. Cox regression analysis was used to screen survival-related genes, and finally, the R package Venn Diagram was used to take the intersection and obtain 7 hub genes. The time-dependent ROC curve and Kaplan–Meier survival curve were used to find the SERPINE1 gene, which plays a critical role in prognosis. Finally, the expression pattern, clinical characteristics, and regulatory mechanism of SERPINE1 were analyzed in STAD. We revealed that the expression of SERPINE1 was significantly increased in the samples from STAD compared with normal samples. Cox regression, time-dependent ROC, and Kaplan–Meier survival analyses demonstrated that SERPINE1 was significantly related to the adverse prognosis of STAD patients. The expression of SERPINE1 increased with the progression of T, N, and M classification of the tumor. In addition, the results of immune infiltration analysis indicated that the immune cells’ expression were higher in high SERPINE1 expression group than that in low SERPINE1 expression group, including CD4(+) T cells, B cells, CD8(+) T cells, macrophages, neutrophils and other immune cells. SERPINE1 was closely related to immune cells in the STAD immune microenvironment and had a synergistic effect with the immune checkpoints PD1 and PD-L1. In conclusion, we proved that SERPINE1 is a promising prognostic and diagnostic biomarker for STAD and a potential target for immunotherapy. Nature Publishing Group UK 2023-01-25 /pmc/articles/PMC9876925/ /pubmed/36697459 http://dx.doi.org/10.1038/s41598-023-28234-7 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Zhai, Yiyan Liu, Xinkui Huang, Zhihong Zhang, Jingyuan Stalin, Antony Tan, Yingying Zhang, Fanqin Chen, Meilin Shi, Rui Huang, Jiaqi Wu, Chao Wu, Zhishan Lu, Shan You, Leiming Wu, Jiarui Data mining combines bioinformatics discover immunoinfiltration-related gene SERPINE1 as a biomarker for diagnosis and prognosis of stomach adenocarcinoma |
title | Data mining combines bioinformatics discover immunoinfiltration-related gene SERPINE1 as a biomarker for diagnosis and prognosis of stomach adenocarcinoma |
title_full | Data mining combines bioinformatics discover immunoinfiltration-related gene SERPINE1 as a biomarker for diagnosis and prognosis of stomach adenocarcinoma |
title_fullStr | Data mining combines bioinformatics discover immunoinfiltration-related gene SERPINE1 as a biomarker for diagnosis and prognosis of stomach adenocarcinoma |
title_full_unstemmed | Data mining combines bioinformatics discover immunoinfiltration-related gene SERPINE1 as a biomarker for diagnosis and prognosis of stomach adenocarcinoma |
title_short | Data mining combines bioinformatics discover immunoinfiltration-related gene SERPINE1 as a biomarker for diagnosis and prognosis of stomach adenocarcinoma |
title_sort | data mining combines bioinformatics discover immunoinfiltration-related gene serpine1 as a biomarker for diagnosis and prognosis of stomach adenocarcinoma |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9876925/ https://www.ncbi.nlm.nih.gov/pubmed/36697459 http://dx.doi.org/10.1038/s41598-023-28234-7 |
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