Yihong Chen, Haicheng Wen, Yin Li, Ying Han, Jun Tan, Cao Guo, Changjing Cai, Ping Liu, Yinghui Peng, Yihan Liu, Xinwen Wang, Shan Zeng, Ziyang Feng, Hong Shen
{"title":"一项多组学分析显示CLSPN与癌症的预后、免疫微环境和耐药性有关。","authors":"Yihong Chen, Haicheng Wen, Yin Li, Ying Han, Jun Tan, Cao Guo, Changjing Cai, Ping Liu, Yinghui Peng, Yihan Liu, Xinwen Wang, Shan Zeng, Ziyang Feng, Hong Shen","doi":"10.1186/s12575-023-00201-6","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Immunotherapy is effective only in limited patients. It is urgent to discover a novel biomarker to predict immune cells infiltration status and immunotherapy response of different cancers. CLSPN has been reported to play a pivotal role in various biological processes. However, a comprehensive analysis of CLSPN in cancers has not been conducted.</p><p><strong>Methods: </strong>To show the whole picture of CLSPN in cancers, a pan-cancer analysis was conducted in 9125 tumor samples across 33 cancer types by integrating transcriptomic, epigenomic and pharmacogenomics data. Moreover, the role of CLSPN in cancer was validated by CCK-8, EDU, colony formation and flow cytometry in vitro and tumor cell derived xenograft model in vivo.</p><p><strong>Results: </strong>CLSPN expression was generally upregulated in most cancer types and was significantly associated with prognosis in different tumor samples. Moreover, elevated CLSPN expression was closely correlated with immune cells infiltration, TMB (tumor mutational burden), MSI (microsatellite instability), MMR (mismatch repair), DNA methylation and stemness score across 33 cancer types. Enrichment analysis of functional genes revealed that CLSPN participated in the regulation of numerous signaling pathways involved in cell cycle and inflammatory response. The expression of CLSPN in LUAD patients were further analyzed at the single-cell level. Knockdown CLSPN significantly inhibited cancer cell proliferation and cell cycle related cyclin-dependent kinase (CDK) family and Cyclin family expression in LUAD (lung adenocarcinoma) both in vitro and in vivo experiments. Finally, we conducted structure-based virtual screening by modelling the structure of CHK1 kinase domain and Claspin phosphopeptide complex. The top five hit compounds were screened and validated by molecular docking and Connectivity Map (CMap) analysis.</p><p><strong>Conclusion: </strong>Our multi-omics analysis offers a systematic understanding of the roles of CLSPN in pan-cancer and provides a potential target for future cancer treatment.</p>","PeriodicalId":8960,"journal":{"name":"Biological Procedures Online","volume":"25 1","pages":"16"},"PeriodicalIF":3.7000,"publicationDate":"2023-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239117/pdf/","citationCount":"0","resultStr":"{\"title\":\"A multi-omics analysis reveals CLSPN is associated with prognosis, immune microenvironment and drug resistance in cancers.\",\"authors\":\"Yihong Chen, Haicheng Wen, Yin Li, Ying Han, Jun Tan, Cao Guo, Changjing Cai, Ping Liu, Yinghui Peng, Yihan Liu, Xinwen Wang, Shan Zeng, Ziyang Feng, Hong Shen\",\"doi\":\"10.1186/s12575-023-00201-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Immunotherapy is effective only in limited patients. It is urgent to discover a novel biomarker to predict immune cells infiltration status and immunotherapy response of different cancers. CLSPN has been reported to play a pivotal role in various biological processes. However, a comprehensive analysis of CLSPN in cancers has not been conducted.</p><p><strong>Methods: </strong>To show the whole picture of CLSPN in cancers, a pan-cancer analysis was conducted in 9125 tumor samples across 33 cancer types by integrating transcriptomic, epigenomic and pharmacogenomics data. Moreover, the role of CLSPN in cancer was validated by CCK-8, EDU, colony formation and flow cytometry in vitro and tumor cell derived xenograft model in vivo.</p><p><strong>Results: </strong>CLSPN expression was generally upregulated in most cancer types and was significantly associated with prognosis in different tumor samples. Moreover, elevated CLSPN expression was closely correlated with immune cells infiltration, TMB (tumor mutational burden), MSI (microsatellite instability), MMR (mismatch repair), DNA methylation and stemness score across 33 cancer types. Enrichment analysis of functional genes revealed that CLSPN participated in the regulation of numerous signaling pathways involved in cell cycle and inflammatory response. The expression of CLSPN in LUAD patients were further analyzed at the single-cell level. Knockdown CLSPN significantly inhibited cancer cell proliferation and cell cycle related cyclin-dependent kinase (CDK) family and Cyclin family expression in LUAD (lung adenocarcinoma) both in vitro and in vivo experiments. Finally, we conducted structure-based virtual screening by modelling the structure of CHK1 kinase domain and Claspin phosphopeptide complex. The top five hit compounds were screened and validated by molecular docking and Connectivity Map (CMap) analysis.</p><p><strong>Conclusion: </strong>Our multi-omics analysis offers a systematic understanding of the roles of CLSPN in pan-cancer and provides a potential target for future cancer treatment.</p>\",\"PeriodicalId\":8960,\"journal\":{\"name\":\"Biological Procedures Online\",\"volume\":\"25 1\",\"pages\":\"16\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2023-06-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10239117/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biological Procedures Online\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s12575-023-00201-6\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMICAL RESEARCH METHODS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biological Procedures Online","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s12575-023-00201-6","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
A multi-omics analysis reveals CLSPN is associated with prognosis, immune microenvironment and drug resistance in cancers.
Background: Immunotherapy is effective only in limited patients. It is urgent to discover a novel biomarker to predict immune cells infiltration status and immunotherapy response of different cancers. CLSPN has been reported to play a pivotal role in various biological processes. However, a comprehensive analysis of CLSPN in cancers has not been conducted.
Methods: To show the whole picture of CLSPN in cancers, a pan-cancer analysis was conducted in 9125 tumor samples across 33 cancer types by integrating transcriptomic, epigenomic and pharmacogenomics data. Moreover, the role of CLSPN in cancer was validated by CCK-8, EDU, colony formation and flow cytometry in vitro and tumor cell derived xenograft model in vivo.
Results: CLSPN expression was generally upregulated in most cancer types and was significantly associated with prognosis in different tumor samples. Moreover, elevated CLSPN expression was closely correlated with immune cells infiltration, TMB (tumor mutational burden), MSI (microsatellite instability), MMR (mismatch repair), DNA methylation and stemness score across 33 cancer types. Enrichment analysis of functional genes revealed that CLSPN participated in the regulation of numerous signaling pathways involved in cell cycle and inflammatory response. The expression of CLSPN in LUAD patients were further analyzed at the single-cell level. Knockdown CLSPN significantly inhibited cancer cell proliferation and cell cycle related cyclin-dependent kinase (CDK) family and Cyclin family expression in LUAD (lung adenocarcinoma) both in vitro and in vivo experiments. Finally, we conducted structure-based virtual screening by modelling the structure of CHK1 kinase domain and Claspin phosphopeptide complex. The top five hit compounds were screened and validated by molecular docking and Connectivity Map (CMap) analysis.
Conclusion: Our multi-omics analysis offers a systematic understanding of the roles of CLSPN in pan-cancer and provides a potential target for future cancer treatment.
期刊介绍：
iological Procedures Online publishes articles that improve access to techniques and methods in the medical and biological sciences.
We are also interested in short but important research discoveries, such as new animal disease models.
Topics of interest include, but are not limited to:
Reports of new research techniques and applications of existing techniques
Technical analyses of research techniques and published reports
Validity analyses of research methods and approaches to judging the validity of research reports
Application of common research methods
Reviews of existing techniques
Novel/important product information
Biological Procedures Online places emphasis on multidisciplinary approaches that integrate methodologies from medicine, biology, chemistry, imaging, engineering, bioinformatics, computer science, and systems analysis.
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