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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

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...

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Autores principales: Zheng, Axiu, Bai, Jianrong, Ha, Yanping, Yu, Yaping, Fan, Yonghao, Liang, Meihua, Lu, Yanda, Shen, Zhihua, Luo, Botao, Jie, Wei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9912524/
https://www.ncbi.nlm.nih.gov/pubmed/36759775
http://dx.doi.org/10.1186/s12885-023-10616-9
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author Zheng, Axiu
Bai, Jianrong
Ha, Yanping
Yu, Yaping
Fan, Yonghao
Liang, Meihua
Lu, Yanda
Shen, Zhihua
Luo, Botao
Jie, Wei
author_facet Zheng, Axiu
Bai, Jianrong
Ha, Yanping
Yu, Yaping
Fan, Yonghao
Liang, Meihua
Lu, Yanda
Shen, Zhihua
Luo, Botao
Jie, Wei
author_sort Zheng, Axiu
collection PubMed
description 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10616-9.
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spelling pubmed-99125242023-02-11 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 Zheng, Axiu Bai, Jianrong Ha, Yanping Yu, Yaping Fan, Yonghao Liang, Meihua Lu, Yanda Shen, Zhihua Luo, Botao Jie, Wei BMC Cancer Research 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. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-023-10616-9. BioMed Central 2023-02-09 /pmc/articles/PMC9912524/ /pubmed/36759775 http://dx.doi.org/10.1186/s12885-023-10616-9 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
Zheng, Axiu
Bai, Jianrong
Ha, Yanping
Yu, Yaping
Fan, Yonghao
Liang, Meihua
Lu, Yanda
Shen, Zhihua
Luo, Botao
Jie, Wei
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 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 Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9912524/
https://www.ncbi.nlm.nih.gov/pubmed/36759775
http://dx.doi.org/10.1186/s12885-023-10616-9
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