Comprehensive analysis of 33 human cancers reveals clinical implications and immunotherapeutic value of the solute carrier family 35 member A2
BackgroundSolute carrier family 35 member A2 (SLC35A2), which belongs to the SLC35 solute carrier family of human nucleoside sugar transporters, has shown regulatory roles in various tumors and neoplasms. However, the function of SLC35A2 across human cancers remains to be systematically assessed. In...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1155182/full |
| _version_ | 1797824083307528192 |
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| author | Shengshan Xu Shengshan Xu Xiguang Chen Jianxiong Fang Hongyu Chu Shuo Fang Leli Zeng Hansu Ma Tianzhi Zhang Yu Chen Tao Wang Xin Zhang Tao Shen Youbin Zheng Dongming Xu Zhuming Lu Yihang Pan Yuchen Liu |
| author_facet | Shengshan Xu Shengshan Xu Xiguang Chen Jianxiong Fang Hongyu Chu Shuo Fang Leli Zeng Hansu Ma Tianzhi Zhang Yu Chen Tao Wang Xin Zhang Tao Shen Youbin Zheng Dongming Xu Zhuming Lu Yihang Pan Yuchen Liu |
| author_sort | Shengshan Xu |
| collection | DOAJ |
| description | BackgroundSolute carrier family 35 member A2 (SLC35A2), which belongs to the SLC35 solute carrier family of human nucleoside sugar transporters, has shown regulatory roles in various tumors and neoplasms. However, the function of SLC35A2 across human cancers remains to be systematically assessed. Insights into the prediction ability of SLC35A2 in clinical practice and immunotherapy response remains limited.Materials and methodsWe obtained the gene expression and protein levels of SLC35A2 in a variety of tumors from Molecular Taxonomy of Breast Cancer International Consortium, The Cancer Genome Atlas, Gene Expression Omnibus, Chinese Glioma Genome Atlas, and Human Protein Atlas databases. The SLC35A2 level was validated by immunohistochemistry. The predictive value for prognosis was evaluated by Kaplan–Meier survival and Cox regression analyses. Correlations between SLC35A2 expression and DNA methylation, genetic alterations, tumor mutation burden (TMB), microsatellite instability (MSI), and tumor microenvironment were performed using Spearman’s correlation analysis. The possible downstream pathways of SLC35A2 in different human cancers were explored using gene set variation analysis. The potential role of SLC35A2 in the tumor immune microenvironment was evaluated via EPIC, CIBERSORT, MCP-counter, CIBERSORT-ABS, quanTIseq, TIMER, and xCell algorithms. The difference in the immunotherapeutic response of SLC35A2 under different expression conditions was evaluated by the tumor immune dysfunction and exclusion (TIDE) score as well as four independent immunotherapy cohorts, which includes patients with bladder urothelial carcinoma (BLCA, N = 299), non–small cell lung cancer (NSCLC, N = 72 and N = 36) and skin cutaneous melanoma (SKCM, N = 25). Potential drugs were identified using the CellMiner database and molecular docking.ResultsSLC35A2 exhibited abnormally high or low expression in 23 cancers and was significantly associated with the prognosis. In various cancers, SLC35A2 expression and mammalian target of rapamycin complex 1 signaling were positively correlated. Multiple algorithmic immune infiltration analyses suggested an inverse relation between SLC35A2 expression and infiltrating immune cells, which includes CD4+T cells, CD8+T cells, B cells, and natural killer cells (NK) in various tumors. Furthermore, SLC35A2 expression was significantly correlated with pan-cancer immune checkpoints, TMB, MSI, and TIDE genes. SLC35A2 showed significant predictive value for the immunotherapy response of patients with diverse cancers. Two drugs, vismodegib and abiraterone, were identified, and the free binding energy of cytochrome P17 with abiraterone was higher than that of SLC35A2 with abiraterone.ConclusionOur study revealed that SLC35A2 is upregulated in 20 types of cancer, including lung adenocarcinoma (LUAD), breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), and lung squamous cell carcinoma (LUSC). The upregulated SLC35A2 in five cancer types indicates a poor prognosis. Furthermore, there was a positive correlation between the overexpression of SLC35A2 and reduced lymphocyte infiltration in 13 cancer types, including BRCA and COAD. Based on data from several clinical trials, patients with LUAD, LUSC, SKCM, and BLCA who exhibited high SLC35A2 expression may experience improved immunotherapy response. Therefore, SLC35A2 could be considered a potential predictive biomarker for the prognosis and immunotherapy efficacy of various tumors. Our study provides a theoretical basis for further investigating its prognostic and therapeutic potentials. |
| first_indexed | 2024-03-13T10:33:43Z |
| format | Article |
| id | doaj.art-139b718ce62d4698be2a129c645bdd95 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-03-13T10:33:43Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-139b718ce62d4698be2a129c645bdd952023-05-18T07:50:44ZengFrontiers Media S.A.Frontiers in Immunology1664-32242023-05-011410.3389/fimmu.2023.11551821155182Comprehensive analysis of 33 human cancers reveals clinical implications and immunotherapeutic value of the solute carrier family 35 member A2Shengshan Xu0Shengshan Xu1Xiguang Chen2Jianxiong Fang3Hongyu Chu4Shuo Fang5Leli Zeng6Hansu Ma7Tianzhi Zhang8Yu Chen9Tao Wang10Xin Zhang11Tao Shen12Youbin Zheng13Dongming Xu14Zhuming Lu15Yihang Pan16Yuchen Liu17Department of Thoracic Surgery, Jiangmen Central Hospital, Jiangmen, Guangdong, ChinaScientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, ChinaDepartment of Medical Oncology, The First Affiliated Hospital of University of South China, Hengyang, Hunan, ChinaDepartment of Urology, Jiangmen Central Hospital, Jiangmen, Guangdong, ChinaDepartment of Gastrointestinal, Colorectal and Anal Surgery, China-Japan Union Hospital of Jilin University, Changchun, ChinaDepartment of Oncology, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, ChinaScientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, ChinaScientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, ChinaDepartment of Pathology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, ChinaScientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, ChinaScientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, ChinaClinical Experimental Center, Jiangmen Key Laboratory of Clinical Biobanks and Translational Research, Jiangmen Central Hospital, Jiangmen, ChinaDepartment of Thoracic Surgery, Jiangmen Central Hospital, Jiangmen, Guangdong, ChinaDepartment of Radiology, Jiangmen Wuyi Hospital of Traditional Chinese Medicine, Jiangmen, Guangdong, China0Department of Neurosurgery, The County Hospital of Qianguo, Songyuan, Jilin, ChinaDepartment of Thoracic Surgery, Jiangmen Central Hospital, Jiangmen, Guangdong, ChinaScientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, ChinaScientific Research Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, Shenzhen, Guangdong, ChinaBackgroundSolute carrier family 35 member A2 (SLC35A2), which belongs to the SLC35 solute carrier family of human nucleoside sugar transporters, has shown regulatory roles in various tumors and neoplasms. However, the function of SLC35A2 across human cancers remains to be systematically assessed. Insights into the prediction ability of SLC35A2 in clinical practice and immunotherapy response remains limited.Materials and methodsWe obtained the gene expression and protein levels of SLC35A2 in a variety of tumors from Molecular Taxonomy of Breast Cancer International Consortium, The Cancer Genome Atlas, Gene Expression Omnibus, Chinese Glioma Genome Atlas, and Human Protein Atlas databases. The SLC35A2 level was validated by immunohistochemistry. The predictive value for prognosis was evaluated by Kaplan–Meier survival and Cox regression analyses. Correlations between SLC35A2 expression and DNA methylation, genetic alterations, tumor mutation burden (TMB), microsatellite instability (MSI), and tumor microenvironment were performed using Spearman’s correlation analysis. The possible downstream pathways of SLC35A2 in different human cancers were explored using gene set variation analysis. The potential role of SLC35A2 in the tumor immune microenvironment was evaluated via EPIC, CIBERSORT, MCP-counter, CIBERSORT-ABS, quanTIseq, TIMER, and xCell algorithms. The difference in the immunotherapeutic response of SLC35A2 under different expression conditions was evaluated by the tumor immune dysfunction and exclusion (TIDE) score as well as four independent immunotherapy cohorts, which includes patients with bladder urothelial carcinoma (BLCA, N = 299), non–small cell lung cancer (NSCLC, N = 72 and N = 36) and skin cutaneous melanoma (SKCM, N = 25). Potential drugs were identified using the CellMiner database and molecular docking.ResultsSLC35A2 exhibited abnormally high or low expression in 23 cancers and was significantly associated with the prognosis. In various cancers, SLC35A2 expression and mammalian target of rapamycin complex 1 signaling were positively correlated. Multiple algorithmic immune infiltration analyses suggested an inverse relation between SLC35A2 expression and infiltrating immune cells, which includes CD4+T cells, CD8+T cells, B cells, and natural killer cells (NK) in various tumors. Furthermore, SLC35A2 expression was significantly correlated with pan-cancer immune checkpoints, TMB, MSI, and TIDE genes. SLC35A2 showed significant predictive value for the immunotherapy response of patients with diverse cancers. Two drugs, vismodegib and abiraterone, were identified, and the free binding energy of cytochrome P17 with abiraterone was higher than that of SLC35A2 with abiraterone.ConclusionOur study revealed that SLC35A2 is upregulated in 20 types of cancer, including lung adenocarcinoma (LUAD), breast invasive carcinoma (BRCA), colon adenocarcinoma (COAD), and lung squamous cell carcinoma (LUSC). The upregulated SLC35A2 in five cancer types indicates a poor prognosis. Furthermore, there was a positive correlation between the overexpression of SLC35A2 and reduced lymphocyte infiltration in 13 cancer types, including BRCA and COAD. Based on data from several clinical trials, patients with LUAD, LUSC, SKCM, and BLCA who exhibited high SLC35A2 expression may experience improved immunotherapy response. Therefore, SLC35A2 could be considered a potential predictive biomarker for the prognosis and immunotherapy efficacy of various tumors. Our study provides a theoretical basis for further investigating its prognostic and therapeutic potentials.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1155182/fullpan-cancer analysisglycosylationSLC35A2tumor microenvironmentimmunotherapy |
| spellingShingle | Shengshan Xu Shengshan Xu Xiguang Chen Jianxiong Fang Hongyu Chu Shuo Fang Leli Zeng Hansu Ma Tianzhi Zhang Yu Chen Tao Wang Xin Zhang Tao Shen Youbin Zheng Dongming Xu Zhuming Lu Yihang Pan Yuchen Liu Comprehensive analysis of 33 human cancers reveals clinical implications and immunotherapeutic value of the solute carrier family 35 member A2 Frontiers in Immunology pan-cancer analysis glycosylation SLC35A2 tumor microenvironment immunotherapy |
| title | Comprehensive analysis of 33 human cancers reveals clinical implications and immunotherapeutic value of the solute carrier family 35 member A2 |
| title_full | Comprehensive analysis of 33 human cancers reveals clinical implications and immunotherapeutic value of the solute carrier family 35 member A2 |
| title_fullStr | Comprehensive analysis of 33 human cancers reveals clinical implications and immunotherapeutic value of the solute carrier family 35 member A2 |
| title_full_unstemmed | Comprehensive analysis of 33 human cancers reveals clinical implications and immunotherapeutic value of the solute carrier family 35 member A2 |
| title_short | Comprehensive analysis of 33 human cancers reveals clinical implications and immunotherapeutic value of the solute carrier family 35 member A2 |
| title_sort | comprehensive analysis of 33 human cancers reveals clinical implications and immunotherapeutic value of the solute carrier family 35 member a2 |
| topic | pan-cancer analysis glycosylation SLC35A2 tumor microenvironment immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2023.1155182/full |
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