Cargando…
SPOCK1 and POSTN are valuable prognostic biomarkers and correlate with tumor immune infiltrates in colorectal cancer
BACKGROUND: Immune cells and stromal cells in the tumor microenvironment play a vital role in the progression of colorectal cancer (CRC). The study aimed to screen valuable prognostic biomarkers in CRC based on stromal and immune scores. METHOD: The ESTIMATE algorithm was used to calculate the immun...
Autores principales: | , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9826581/ https://www.ncbi.nlm.nih.gov/pubmed/36611136 http://dx.doi.org/10.1186/s12876-022-02621-2 |
_version_ | 1784866886291292160 |
---|---|
author | Gan, Caiqin Li, Mengting Lu, Yuanyuan Peng, Ganjing Li, Wenjie Wang, Haizhou Peng, Yanan Hu, Qian Wei, Wanhui Wang, Fan Liu, Lan Zhao, Qiu |
author_facet | Gan, Caiqin Li, Mengting Lu, Yuanyuan Peng, Ganjing Li, Wenjie Wang, Haizhou Peng, Yanan Hu, Qian Wei, Wanhui Wang, Fan Liu, Lan Zhao, Qiu |
author_sort | Gan, Caiqin |
collection | PubMed |
description | BACKGROUND: Immune cells and stromal cells in the tumor microenvironment play a vital role in the progression of colorectal cancer (CRC). The study aimed to screen valuable prognostic biomarkers in CRC based on stromal and immune scores. METHOD: The ESTIMATE algorithm was used to calculate the immune and stromal scores of CRC samples in TCGA. Then samples were divided into high and low score groups based on the median value of the scores. Differentially expressed genes (DEGs) associated with immune and stromal scores were screened. WGCNA and univariate COX regression analysis were performed to further identify key prognostic genes. Analysis of scRNA-seq for CRC was used for verifying the main source of the key genes. The prognostic value of they was validated based on The Gene Expression Profiling Interactive Analysis and GSE17536 dataset. TIMER and CIBERSORT algorithms were applied to analyze the correlations among key genes and tumor-infiltrating immune cells. Several pairs of colon cancer tissue were used to be proven. RESULT: 1314 upregulated and 4 downregulated genes were identified, which were significantly enriched in immune-related biological processes and pathways. Among these DEGs, SPOCK1 and POSTN were identified as key prognostic genes and mainly expressed in cancer-associated fibroblasts for CRC. High expression of SPCOK1 and POSTN was associated with advanced clinical stage, T stage, N stage, and poor prognosis of CRC. The results from CIBERSORT and TIMER revealed that SPOCK1 and POSTN were associated with tumor-infiltrating immune cells, especially macrophages and neutrophils. Meanwhile, in several pairs of human colorectal tissue samples, SPOK1 and POSTN were found to be significantly overexpressed in colorectal tissue compared with para-cancer tissue, and macrophage surface markers CD68 (co-expressed by M1 and M2 macrophages) and CD206 (M2-specific macrophage expression) were also overexpressed in cancer tissue. Besides, SPOCK1 and POSTN expression were positively correlated with the expression of immune checkpoints. CONCLUSION: Collectively, our results indicate that SPOCK1 and POSTN associated with CAF may be novel prognostic biomarkers in CRC and correlate with immune infiltrates. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12876-022-02621-2. |
format | Online Article Text |
id | pubmed-9826581 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-98265812023-01-09 SPOCK1 and POSTN are valuable prognostic biomarkers and correlate with tumor immune infiltrates in colorectal cancer Gan, Caiqin Li, Mengting Lu, Yuanyuan Peng, Ganjing Li, Wenjie Wang, Haizhou Peng, Yanan Hu, Qian Wei, Wanhui Wang, Fan Liu, Lan Zhao, Qiu BMC Gastroenterol Research BACKGROUND: Immune cells and stromal cells in the tumor microenvironment play a vital role in the progression of colorectal cancer (CRC). The study aimed to screen valuable prognostic biomarkers in CRC based on stromal and immune scores. METHOD: The ESTIMATE algorithm was used to calculate the immune and stromal scores of CRC samples in TCGA. Then samples were divided into high and low score groups based on the median value of the scores. Differentially expressed genes (DEGs) associated with immune and stromal scores were screened. WGCNA and univariate COX regression analysis were performed to further identify key prognostic genes. Analysis of scRNA-seq for CRC was used for verifying the main source of the key genes. The prognostic value of they was validated based on The Gene Expression Profiling Interactive Analysis and GSE17536 dataset. TIMER and CIBERSORT algorithms were applied to analyze the correlations among key genes and tumor-infiltrating immune cells. Several pairs of colon cancer tissue were used to be proven. RESULT: 1314 upregulated and 4 downregulated genes were identified, which were significantly enriched in immune-related biological processes and pathways. Among these DEGs, SPOCK1 and POSTN were identified as key prognostic genes and mainly expressed in cancer-associated fibroblasts for CRC. High expression of SPCOK1 and POSTN was associated with advanced clinical stage, T stage, N stage, and poor prognosis of CRC. The results from CIBERSORT and TIMER revealed that SPOCK1 and POSTN were associated with tumor-infiltrating immune cells, especially macrophages and neutrophils. Meanwhile, in several pairs of human colorectal tissue samples, SPOK1 and POSTN were found to be significantly overexpressed in colorectal tissue compared with para-cancer tissue, and macrophage surface markers CD68 (co-expressed by M1 and M2 macrophages) and CD206 (M2-specific macrophage expression) were also overexpressed in cancer tissue. Besides, SPOCK1 and POSTN expression were positively correlated with the expression of immune checkpoints. CONCLUSION: Collectively, our results indicate that SPOCK1 and POSTN associated with CAF may be novel prognostic biomarkers in CRC and correlate with immune infiltrates. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12876-022-02621-2. BioMed Central 2023-01-07 /pmc/articles/PMC9826581/ /pubmed/36611136 http://dx.doi.org/10.1186/s12876-022-02621-2 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis 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/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Gan, Caiqin Li, Mengting Lu, Yuanyuan Peng, Ganjing Li, Wenjie Wang, Haizhou Peng, Yanan Hu, Qian Wei, Wanhui Wang, Fan Liu, Lan Zhao, Qiu SPOCK1 and POSTN are valuable prognostic biomarkers and correlate with tumor immune infiltrates in colorectal cancer |
title | SPOCK1 and POSTN are valuable prognostic biomarkers and correlate with tumor immune infiltrates in colorectal cancer |
title_full | SPOCK1 and POSTN are valuable prognostic biomarkers and correlate with tumor immune infiltrates in colorectal cancer |
title_fullStr | SPOCK1 and POSTN are valuable prognostic biomarkers and correlate with tumor immune infiltrates in colorectal cancer |
title_full_unstemmed | SPOCK1 and POSTN are valuable prognostic biomarkers and correlate with tumor immune infiltrates in colorectal cancer |
title_short | SPOCK1 and POSTN are valuable prognostic biomarkers and correlate with tumor immune infiltrates in colorectal cancer |
title_sort | spock1 and postn are valuable prognostic biomarkers and correlate with tumor immune infiltrates in colorectal cancer |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9826581/ https://www.ncbi.nlm.nih.gov/pubmed/36611136 http://dx.doi.org/10.1186/s12876-022-02621-2 |
work_keys_str_mv | AT gancaiqin spock1andpostnarevaluableprognosticbiomarkersandcorrelatewithtumorimmuneinfiltratesincolorectalcancer AT limengting spock1andpostnarevaluableprognosticbiomarkersandcorrelatewithtumorimmuneinfiltratesincolorectalcancer AT luyuanyuan spock1andpostnarevaluableprognosticbiomarkersandcorrelatewithtumorimmuneinfiltratesincolorectalcancer AT pengganjing spock1andpostnarevaluableprognosticbiomarkersandcorrelatewithtumorimmuneinfiltratesincolorectalcancer AT liwenjie spock1andpostnarevaluableprognosticbiomarkersandcorrelatewithtumorimmuneinfiltratesincolorectalcancer AT wanghaizhou spock1andpostnarevaluableprognosticbiomarkersandcorrelatewithtumorimmuneinfiltratesincolorectalcancer AT pengyanan spock1andpostnarevaluableprognosticbiomarkersandcorrelatewithtumorimmuneinfiltratesincolorectalcancer AT huqian spock1andpostnarevaluableprognosticbiomarkersandcorrelatewithtumorimmuneinfiltratesincolorectalcancer AT weiwanhui spock1andpostnarevaluableprognosticbiomarkersandcorrelatewithtumorimmuneinfiltratesincolorectalcancer AT wangfan spock1andpostnarevaluableprognosticbiomarkersandcorrelatewithtumorimmuneinfiltratesincolorectalcancer AT liulan spock1andpostnarevaluableprognosticbiomarkersandcorrelatewithtumorimmuneinfiltratesincolorectalcancer AT zhaoqiu spock1andpostnarevaluableprognosticbiomarkersandcorrelatewithtumorimmuneinfiltratesincolorectalcancer |