Immune Infiltration, Cancer Stemness, and Targeted Therapy in Gastrointestinal Stromal Tumor

ObjectiveTo investigate the characteristics of the tumor immune microenvironment in patients with gastrointestinal stromal tumor (GIST) and identify cancer stem-like properties of GIST to screen potential druggable molecular targets.MethodsThe gene expression data of 60 patients with GIST was retrie...

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Autores principales:	Jingjing Wang, Hui Ren, Wenhui Wu, Qianlin Zeng, Jingyao Chen, Juanjuan Han, Minquan Lin, Changhua Zhang, Yulong He, Mingzhe Li
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	gastrointestinal stromal tumor targeted therapy immune infiltration cancer stem cells tumor immune microenvironment Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/73a7be628fcc4467a38e004de0bebabd
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spelling	oai:doaj.org-article:73a7be628fcc4467a38e004de0bebabd2021-12-03T05:25:38ZImmune Infiltration, Cancer Stemness, and Targeted Therapy in Gastrointestinal Stromal Tumor1664-322410.3389/fimmu.2021.691713https://doaj.org/article/73a7be628fcc4467a38e004de0bebabd2021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.691713/fullhttps://doaj.org/toc/1664-3224ObjectiveTo investigate the characteristics of the tumor immune microenvironment in patients with gastrointestinal stromal tumor (GIST) and identify cancer stem-like properties of GIST to screen potential druggable molecular targets.MethodsThe gene expression data of 60 patients with GIST was retrieved from the Array Express database. CIBERSORT was applied to calculate the level of immune infiltration. ssGSEA and ESTIMATE were used to calculate the cancer stemness index and tissue purity. The Connectivity Map (CMAP) database was implemented to screen targeted drugs based on cancer stem-like properties of GIST.ResultThere was a difference in the level of immune infiltration between the metastasis and non-metastasis GIST groups. The low level of T-cell infiltration was correlated with high tumor purity and tumor stemness index, and the correlation coefficients were -0.87 and -0.61 (p < 0.001), respectively. Furthermore, there was a positive correlation between cancer stemness index and cell purity (p < 0.001). The cancer stemness index in the metastasis group was higher than that in the non-metastasis group (p = 0.0017). After adjusting for tumor purity, there was no significant correlation between T-cell infiltration and cancer stemness index (p = 0.086). Through the pharmacological mechanism of topoisomerase inhibitors, six molecular complexes may be the targets of GIST treatment.ConclusionImmune infiltration in GIST patients is related to cancer stem-like properties, and the correlation relies on tumor purity. Cancer stemness index can be used as a new predictive biomarker of tumor metastasis and targets of drug therapy for GIST patients.Jingjing WangHui RenWenhui WuQianlin ZengJingyao ChenJuanjuan HanMinquan LinChanghua ZhangYulong HeMingzhe LiFrontiers Media S.A.articlegastrointestinal stromal tumortargeted therapyimmune infiltrationcancer stem cellstumor immune microenvironmentImmunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	gastrointestinal stromal tumor targeted therapy immune infiltration cancer stem cells tumor immune microenvironment Immunologic diseases. Allergy RC581-607
spellingShingle	gastrointestinal stromal tumor targeted therapy immune infiltration cancer stem cells tumor immune microenvironment Immunologic diseases. Allergy RC581-607 Jingjing Wang Hui Ren Wenhui Wu Qianlin Zeng Jingyao Chen Juanjuan Han Minquan Lin Changhua Zhang Yulong He Mingzhe Li Immune Infiltration, Cancer Stemness, and Targeted Therapy in Gastrointestinal Stromal Tumor
description	ObjectiveTo investigate the characteristics of the tumor immune microenvironment in patients with gastrointestinal stromal tumor (GIST) and identify cancer stem-like properties of GIST to screen potential druggable molecular targets.MethodsThe gene expression data of 60 patients with GIST was retrieved from the Array Express database. CIBERSORT was applied to calculate the level of immune infiltration. ssGSEA and ESTIMATE were used to calculate the cancer stemness index and tissue purity. The Connectivity Map (CMAP) database was implemented to screen targeted drugs based on cancer stem-like properties of GIST.ResultThere was a difference in the level of immune infiltration between the metastasis and non-metastasis GIST groups. The low level of T-cell infiltration was correlated with high tumor purity and tumor stemness index, and the correlation coefficients were -0.87 and -0.61 (p < 0.001), respectively. Furthermore, there was a positive correlation between cancer stemness index and cell purity (p < 0.001). The cancer stemness index in the metastasis group was higher than that in the non-metastasis group (p = 0.0017). After adjusting for tumor purity, there was no significant correlation between T-cell infiltration and cancer stemness index (p = 0.086). Through the pharmacological mechanism of topoisomerase inhibitors, six molecular complexes may be the targets of GIST treatment.ConclusionImmune infiltration in GIST patients is related to cancer stem-like properties, and the correlation relies on tumor purity. Cancer stemness index can be used as a new predictive biomarker of tumor metastasis and targets of drug therapy for GIST patients.
format	article
author	Jingjing Wang Hui Ren Wenhui Wu Qianlin Zeng Jingyao Chen Juanjuan Han Minquan Lin Changhua Zhang Yulong He Mingzhe Li
author_facet	Jingjing Wang Hui Ren Wenhui Wu Qianlin Zeng Jingyao Chen Juanjuan Han Minquan Lin Changhua Zhang Yulong He Mingzhe Li
author_sort	Jingjing Wang
title	Immune Infiltration, Cancer Stemness, and Targeted Therapy in Gastrointestinal Stromal Tumor
title_short	Immune Infiltration, Cancer Stemness, and Targeted Therapy in Gastrointestinal Stromal Tumor
title_full	Immune Infiltration, Cancer Stemness, and Targeted Therapy in Gastrointestinal Stromal Tumor
title_fullStr	Immune Infiltration, Cancer Stemness, and Targeted Therapy in Gastrointestinal Stromal Tumor
title_full_unstemmed	Immune Infiltration, Cancer Stemness, and Targeted Therapy in Gastrointestinal Stromal Tumor
title_sort	immune infiltration, cancer stemness, and targeted therapy in gastrointestinal stromal tumor
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/73a7be628fcc4467a38e004de0bebabd
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Immune Infiltration, Cancer Stemness, and Targeted Therapy in Gastrointestinal Stromal Tumor

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