Integrated analysis of the relation to tumor immune microenvironment and predicted value of Stonin1 gene for immune checkpoint blockage and targeted treatment in kidney renal clear cell carcinoma

Abstract Background Stonin1 (STON1) is an endocytic protein but its role in cancer remains unclear. Here, we investigated the immune role of STON1 in kidney renal clear cell carcinoma (KIRC). Methods We undertook bioinformatics analyses of the expression and clinical significance of STON1 in KIRC th...

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Main Authors: Axiu Zheng, Jianrong Bai, Yanping Ha, Yaping Yu, Yonghao Fan, Meihua Liang, Yanda Lu, Zhihua Shen, Botao Luo, Wei Jie
Format: Article
Language:English
Published: BMC 2023-02-01
Series:BMC Cancer
Subjects:
Online Access:https://doi.org/10.1186/s12885-023-10616-9
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author Axiu Zheng
Jianrong Bai
Yanping Ha
Yaping Yu
Yonghao Fan
Meihua Liang
Yanda Lu
Zhihua Shen
Botao Luo
Wei Jie
author_facet Axiu Zheng
Jianrong Bai
Yanping Ha
Yaping Yu
Yonghao Fan
Meihua Liang
Yanda Lu
Zhihua Shen
Botao Luo
Wei Jie
author_sort Axiu Zheng
collection DOAJ
description Abstract Background Stonin1 (STON1) is an endocytic protein but its role in cancer remains unclear. Here, we investigated the immune role of STON1 in kidney renal clear cell carcinoma (KIRC). Methods We undertook bioinformatics analyses of the expression and clinical significance of STON1 in KIRC through a series of public databases, and the role of STON1 in the tumor microenvironment and the predictive value for immunotherapy and targeted treatment in KIRC were identified with R packages. STON1 expression was validated in clinical KIRC tissues as well as in KIRC and normal renal tubular epithelial cells. Results Through public databases, STON1 mRNA was found to be significantly downregulated in KIRC compared with normal controls, and decreased STON1 was related to grade, TNM stage, distant metastasis and status of KIRC patients. Compared with normal controls, STON1 was found to be downregulated in KIRC tissues and cell lines. Furthermore, OncoLnc, Kaplan–Meier, and GEPIA2 analyses also suggested that KIRC patients with high STON1 expression had better overall survival. The high STON1 group with enriched immune cells had a more favorable prognosis than the low STON1 group with decreased immune cells. Single sample Gene Set Enrichment Analysis and Gene Set Variation Analysis indicated that STON1 creates an immune non-inflamed phenotype in KIRC. Moreover, STON1 was positively associated with mismatch repair proteins and negatively correlated with tumor mutational burden. Furthermore, Single sample Gene Set Enrichment Analysis algorithm and Pearson analysis found that the low STON1 group was more sensitive to immune checkpoint blockage whereas the high STON1 group was relatively suitable for targeted treatment. Conclusions Decreased STON1 expression in KIRC leads to clinical progression and poor survival. Mechanically, low STON1 expression is associated with an aberrant tumor immune microenvironment. Low STON1 is likely to be a favorable indicator for immunotherapy response but adverse indicator for targeted therapeutics in KIRC.
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spelling doaj.art-f1f06e3619d84870a986a9226fa1e9c02023-02-12T12:14:46ZengBMCBMC Cancer1471-24072023-02-0123111810.1186/s12885-023-10616-9Integrated analysis of the relation to tumor immune microenvironment and predicted value of Stonin1 gene for immune checkpoint blockage and targeted treatment in kidney renal clear cell carcinomaAxiu Zheng0Jianrong Bai1Yanping Ha2Yaping Yu3Yonghao Fan4Meihua Liang5Yanda Lu6Zhihua Shen7Botao Luo8Wei Jie9Department of Pathology, School of Basic Medicine Sciences; Pathology Diagnosis and Research Center of Affiliated Hospital, Guangdong Medical UniversityDepartment of Pathology, School of Basic Medicine Sciences; Pathology Diagnosis and Research Center of Affiliated Hospital, Guangdong Medical UniversityDepartment of Pathology, School of Basic Medicine Sciences; Pathology Diagnosis and Research Center of Affiliated Hospital, Guangdong Medical UniversityDepartment of Oncology of the First Affliated Hospital; Oncology Institute, Hainan Medical UniversityDepartment of Oncology of the First Affliated Hospital; Oncology Institute, Hainan Medical UniversityDepartment of Pathology, School of Basic Medicine Sciences; Pathology Diagnosis and Research Center of Affiliated Hospital, Guangdong Medical UniversityDepartment of Oncology of the First Affliated Hospital; Oncology Institute, Hainan Medical UniversityDepartment of Pathology, School of Basic Medicine Sciences; Pathology Diagnosis and Research Center of Affiliated Hospital, Guangdong Medical UniversityDepartment of Pathology, School of Basic Medicine Sciences; Pathology Diagnosis and Research Center of Affiliated Hospital, Guangdong Medical UniversityDepartment of Pathology, School of Basic Medicine Sciences; Pathology Diagnosis and Research Center of Affiliated Hospital, Guangdong Medical UniversityAbstract Background Stonin1 (STON1) is an endocytic protein but its role in cancer remains unclear. Here, we investigated the immune role of STON1 in kidney renal clear cell carcinoma (KIRC). Methods We undertook bioinformatics analyses of the expression and clinical significance of STON1 in KIRC through a series of public databases, and the role of STON1 in the tumor microenvironment and the predictive value for immunotherapy and targeted treatment in KIRC were identified with R packages. STON1 expression was validated in clinical KIRC tissues as well as in KIRC and normal renal tubular epithelial cells. Results Through public databases, STON1 mRNA was found to be significantly downregulated in KIRC compared with normal controls, and decreased STON1 was related to grade, TNM stage, distant metastasis and status of KIRC patients. Compared with normal controls, STON1 was found to be downregulated in KIRC tissues and cell lines. Furthermore, OncoLnc, Kaplan–Meier, and GEPIA2 analyses also suggested that KIRC patients with high STON1 expression had better overall survival. The high STON1 group with enriched immune cells had a more favorable prognosis than the low STON1 group with decreased immune cells. Single sample Gene Set Enrichment Analysis and Gene Set Variation Analysis indicated that STON1 creates an immune non-inflamed phenotype in KIRC. Moreover, STON1 was positively associated with mismatch repair proteins and negatively correlated with tumor mutational burden. Furthermore, Single sample Gene Set Enrichment Analysis algorithm and Pearson analysis found that the low STON1 group was more sensitive to immune checkpoint blockage whereas the high STON1 group was relatively suitable for targeted treatment. Conclusions Decreased STON1 expression in KIRC leads to clinical progression and poor survival. Mechanically, low STON1 expression is associated with an aberrant tumor immune microenvironment. Low STON1 is likely to be a favorable indicator for immunotherapy response but adverse indicator for targeted therapeutics in KIRC.https://doi.org/10.1186/s12885-023-10616-9Stonin1Kidney renal clear cell carcinomaTumor immune microenvironmentImmune checkpoint blockageImmunotherapy responseTargeted therapeutics
spellingShingle Axiu Zheng
Jianrong Bai
Yanping Ha
Yaping Yu
Yonghao Fan
Meihua Liang
Yanda Lu
Zhihua Shen
Botao Luo
Wei Jie
Integrated analysis of the relation to tumor immune microenvironment and predicted value of Stonin1 gene for immune checkpoint blockage and targeted treatment in kidney renal clear cell carcinoma
BMC Cancer
Stonin1
Kidney renal clear cell carcinoma
Tumor immune microenvironment
Immune checkpoint blockage
Immunotherapy response
Targeted therapeutics
title Integrated analysis of the relation to tumor immune microenvironment and predicted value of Stonin1 gene for immune checkpoint blockage and targeted treatment in kidney renal clear cell carcinoma
title_full Integrated analysis of the relation to tumor immune microenvironment and predicted value of Stonin1 gene for immune checkpoint blockage and targeted treatment in kidney renal clear cell carcinoma
title_fullStr Integrated analysis of the relation to tumor immune microenvironment and predicted value of Stonin1 gene for immune checkpoint blockage and targeted treatment in kidney renal clear cell carcinoma
title_full_unstemmed Integrated analysis of the relation to tumor immune microenvironment and predicted value of Stonin1 gene for immune checkpoint blockage and targeted treatment in kidney renal clear cell carcinoma
title_short Integrated analysis of the relation to tumor immune microenvironment and predicted value of Stonin1 gene for immune checkpoint blockage and targeted treatment in kidney renal clear cell carcinoma
title_sort integrated analysis of the relation to tumor immune microenvironment and predicted value of stonin1 gene for immune checkpoint blockage and targeted treatment in kidney renal clear cell carcinoma
topic Stonin1
Kidney renal clear cell carcinoma
Tumor immune microenvironment
Immune checkpoint blockage
Immunotherapy response
Targeted therapeutics
url https://doi.org/10.1186/s12885-023-10616-9
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