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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Main Authors: Jingjing Wang, Hui Ren, Wenhui Wu, Qianlin Zeng, Jingyao Chen, Juanjuan Han, Minquan Lin, Changhua Zhang, Yulong He, Mingzhe Li
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-12-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2021.691713/full
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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
collection DOAJ
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.
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spelling doaj.art-73a7be628fcc4467a38e004de0bebabd2022-12-21T19:28:11ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-12-011210.3389/fimmu.2021.691713691713Immune Infiltration, Cancer Stemness, and Targeted Therapy in Gastrointestinal Stromal TumorJingjing Wang0Hui Ren1Wenhui Wu2Qianlin Zeng3Jingyao Chen4Juanjuan Han5Minquan Lin6Changhua Zhang7Yulong He8Mingzhe Li9Department of Laboratory, Hexian Memorial Hospital of Panyu District, Guangzhou, ChinaDigestive Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaDigestive Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaDigestive Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaDigestive Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaDepartment of Laboratory, Hexian Memorial Hospital of Panyu District, Guangzhou, ChinaDepartment of Laboratory, Hexian Memorial Hospital of Panyu District, Guangzhou, ChinaDigestive Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaDigestive Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaDigestive Medicine Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, ChinaObjectiveTo 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.https://www.frontiersin.org/articles/10.3389/fimmu.2021.691713/fullgastrointestinal stromal tumortargeted therapyimmune infiltrationcancer stem cellstumor immune microenvironment
spellingShingle 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
Frontiers in Immunology
gastrointestinal stromal tumor
targeted therapy
immune infiltration
cancer stem cells
tumor immune microenvironment
title 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_short Immune Infiltration, Cancer Stemness, and Targeted Therapy in Gastrointestinal Stromal Tumor
title_sort immune infiltration cancer stemness and targeted therapy in gastrointestinal stromal tumor
topic gastrointestinal stromal tumor
targeted therapy
immune infiltration
cancer stem cells
tumor immune microenvironment
url https://www.frontiersin.org/articles/10.3389/fimmu.2021.691713/full
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