The Epithelial and Stromal Immune Microenvironment in Gastric Cancer: A Comprehensive Analysis Reveals Prognostic Factors with Digital Cytometry

Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Tumor heterogeneity continues to confound researchers’ understanding of tumor growth and the development of an effective therapy. Digital cytometry allows interpretation of heterogeneous bulk tissue transcriptomes at...

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Autores principales:	Wenjun Shen, Guoyun Wang, Georgia R. Cooper, Yuming Jiang, Xin Zhou
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	gastric cancer tumor microenvironment scRNA-seq cell mixture deconvolution Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/d072d93d38de4a29a48c6b2c70a110d8
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spelling	oai:doaj.org-article:d072d93d38de4a29a48c6b2c70a110d82021-11-11T15:29:41ZThe Epithelial and Stromal Immune Microenvironment in Gastric Cancer: A Comprehensive Analysis Reveals Prognostic Factors with Digital Cytometry10.3390/cancers132153822072-6694https://doaj.org/article/d072d93d38de4a29a48c6b2c70a110d82021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5382https://doaj.org/toc/2072-6694Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Tumor heterogeneity continues to confound researchers’ understanding of tumor growth and the development of an effective therapy. Digital cytometry allows interpretation of heterogeneous bulk tissue transcriptomes at the cellular level. We built a novel signature matrix to dissect epithelium and stroma signals using a scRNA-seq data set (GSE134520) for GC and then applied cell mixture deconvolution to estimate diverse epithelial, stromal, and immune cell proportions from bulk transcriptome data in four independent GC cohorts (GSE62254, GSE15459, GSE84437, and TCGA-STAD) from the GEO and TCGA databases. Robust computational methods were applied to identify strong prognostic factors for GC. We identified an EMEC population whose proportions were significantly higher in patients with stage I cancer than other stages, and it was predominantly present in tumor samples but not typically found in normal samples. We found that the ratio of EMECs to stromal cells and the ratio of adaptive T cells to monocytes were the most significant prognostic factors within the non-immune and immune factors, respectively. The STEM score, which unifies these two prognostic factors, was an independent prognostic factor of overall survival (HR = 0.92, <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mn>95</mn><mo>%</mo></mrow></semantics></math></inline-formula> CI = 0.89–0.94, <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>p</mi><mo>=</mo><mn>2.05</mn><mo>×</mo><msup><mn>10</mn><mrow><mo>−</mo><mn>9</mn></mrow></msup></mrow></semantics></math></inline-formula>). The entire GC cohort was stratified into three risk groups (high-, moderate-, and low-risk), which yielded incremental survival times (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>p</mi><mo><</mo><mn>0.0001</mn></mrow></semantics></math></inline-formula>). For stage III disease, patients in the moderate- and low-risk groups experienced better survival benefits from radiation therapy ((HR = 0.16, 95% CI = 0.06–0.4, <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>p</mi><mo><</mo><mn>0.0001</mn></mrow></semantics></math></inline-formula>), whereas those in the high-risk group did not (HR = 0.49, 95% CI = 0.14–1.72, <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>p</mi><mo>=</mo><mn>0.25</mn></mrow></semantics></math></inline-formula>). We concluded that the STEM score is a promising prognostic factor for gastric cancer.Wenjun ShenGuoyun WangGeorgia R. CooperYuming JiangXin ZhouMDPI AGarticlegastric cancertumor microenvironmentscRNA-seqcell mixture deconvolutionNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5382, p 5382 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	gastric cancer tumor microenvironment scRNA-seq cell mixture deconvolution Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	gastric cancer tumor microenvironment scRNA-seq cell mixture deconvolution Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Wenjun Shen Guoyun Wang Georgia R. Cooper Yuming Jiang Xin Zhou The Epithelial and Stromal Immune Microenvironment in Gastric Cancer: A Comprehensive Analysis Reveals Prognostic Factors with Digital Cytometry
description	Gastric cancer (GC) is the third leading cause of cancer-related deaths worldwide. Tumor heterogeneity continues to confound researchers’ understanding of tumor growth and the development of an effective therapy. Digital cytometry allows interpretation of heterogeneous bulk tissue transcriptomes at the cellular level. We built a novel signature matrix to dissect epithelium and stroma signals using a scRNA-seq data set (GSE134520) for GC and then applied cell mixture deconvolution to estimate diverse epithelial, stromal, and immune cell proportions from bulk transcriptome data in four independent GC cohorts (GSE62254, GSE15459, GSE84437, and TCGA-STAD) from the GEO and TCGA databases. Robust computational methods were applied to identify strong prognostic factors for GC. We identified an EMEC population whose proportions were significantly higher in patients with stage I cancer than other stages, and it was predominantly present in tumor samples but not typically found in normal samples. We found that the ratio of EMECs to stromal cells and the ratio of adaptive T cells to monocytes were the most significant prognostic factors within the non-immune and immune factors, respectively. The STEM score, which unifies these two prognostic factors, was an independent prognostic factor of overall survival (HR = 0.92, <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mn>95</mn><mo>%</mo></mrow></semantics></math></inline-formula> CI = 0.89–0.94, <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>p</mi><mo>=</mo><mn>2.05</mn><mo>×</mo><msup><mn>10</mn><mrow><mo>−</mo><mn>9</mn></mrow></msup></mrow></semantics></math></inline-formula>). The entire GC cohort was stratified into three risk groups (high-, moderate-, and low-risk), which yielded incremental survival times (<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>p</mi><mo><</mo><mn>0.0001</mn></mrow></semantics></math></inline-formula>). For stage III disease, patients in the moderate- and low-risk groups experienced better survival benefits from radiation therapy ((HR = 0.16, 95% CI = 0.06–0.4, <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>p</mi><mo><</mo><mn>0.0001</mn></mrow></semantics></math></inline-formula>), whereas those in the high-risk group did not (HR = 0.49, 95% CI = 0.14–1.72, <inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mrow><mi>p</mi><mo>=</mo><mn>0.25</mn></mrow></semantics></math></inline-formula>). We concluded that the STEM score is a promising prognostic factor for gastric cancer.
format	article
author	Wenjun Shen Guoyun Wang Georgia R. Cooper Yuming Jiang Xin Zhou
author_facet	Wenjun Shen Guoyun Wang Georgia R. Cooper Yuming Jiang Xin Zhou
author_sort	Wenjun Shen
title	The Epithelial and Stromal Immune Microenvironment in Gastric Cancer: A Comprehensive Analysis Reveals Prognostic Factors with Digital Cytometry
title_short	The Epithelial and Stromal Immune Microenvironment in Gastric Cancer: A Comprehensive Analysis Reveals Prognostic Factors with Digital Cytometry
title_full	The Epithelial and Stromal Immune Microenvironment in Gastric Cancer: A Comprehensive Analysis Reveals Prognostic Factors with Digital Cytometry
title_fullStr	The Epithelial and Stromal Immune Microenvironment in Gastric Cancer: A Comprehensive Analysis Reveals Prognostic Factors with Digital Cytometry
title_full_unstemmed	The Epithelial and Stromal Immune Microenvironment in Gastric Cancer: A Comprehensive Analysis Reveals Prognostic Factors with Digital Cytometry
title_sort	epithelial and stromal immune microenvironment in gastric cancer: a comprehensive analysis reveals prognostic factors with digital cytometry
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/d072d93d38de4a29a48c6b2c70a110d8
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The Epithelial and Stromal Immune Microenvironment in Gastric Cancer: A Comprehensive Analysis Reveals Prognostic Factors with Digital Cytometry

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