Jing Zeng, Grayson Way, Nan Wu, Xixian Jiang, Yun-Ling Tai, Derrick Zhao, Lianyong Su, Qianhua Yan, Xuan Wang, Emily C Gurley, Phillip B Hylemon, Sayed Obaidullah Aseem, Arun J Sanyal, Jiangao Fan, Huiping Zhou
{"title":"转录组学、脂质组学和单核RNA测序整合：探索鞘脂在MASH-HCC进展中的作用。","authors":"Jing Zeng, Grayson Way, Nan Wu, Xixian Jiang, Yun-Ling Tai, Derrick Zhao, Lianyong Su, Qianhua Yan, Xuan Wang, Emily C Gurley, Phillip B Hylemon, Sayed Obaidullah Aseem, Arun J Sanyal, Jiangao Fan, Huiping Zhou","doi":"10.1186/s13578-025-01362-5","DOIUrl":null,"url":null,"abstract":"<p><strong>Background & aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses various conditions, ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. MASLD is a significant risk factor for hepatocellular carcinoma (HCC) and is rapidly becoming the primary cause of liver transplantation. Dysregulated sphingolipid metabolism has been linked to the development of MASH-HCC. However, detailed insight into the sphingolipid profiles and cell type-specific changes in key genes involved in sphingolipid metabolism remains limited and forms the primary focus of this study.</p><p><strong>Approaches & results: </strong>This study used the well-characterized diet-induced MASH-HCC mouse model (DIAMOND). Total RNA sequencing data, NanoString nCounter<sup>®</sup> Gene profiling, and single-nucleus RNA sequencing (snRNA-seq) GEO data (GSE225381) were used in characterizing gene regulation in MASH-HCC progression. Sphingolipids in the serum and liver were profiled using targeted lipidomics. RNA data analysis showed dysregulation of key genes involved in sphingolipid metabolism, including ceramide synthase 6 (Cers6), serine palmitoyltransferase long chain base subunit 2 (Sptlc2), sphingosine kinase 2 (SphK2), and sphingosine-1-phosphate receptor 1-3 (S1pr1-3) which paralleled significant changes in sphingolipid composition and levels in both serum and liver. Furthermore, TCGA-LIHC patient data were analyzed and potential prognostic genes for MASH-HCC were identified using univariate and multivariate Cox analysis. The multivariate Cox analysis underscored the prognostic significance of several genes related to sphingolipid metabolism, including CERS6, SPTLC2, and S1PR1.</p><p><strong>Conclusion: </strong>Our findings provided valuable insights into the role of sphingolipids in the progression of MASH to HCC. Specific serum and liver sphingolipid profiles may serve as valuable biomarkers for diagnosis and prognosis in MASH-HCC.</p>","PeriodicalId":49095,"journal":{"name":"Cell and Bioscience","volume":"15 1","pages":"34"},"PeriodicalIF":6.1000,"publicationDate":"2025-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890728/pdf/","citationCount":"0","resultStr":"{\"title\":\"Transcriptomics, lipidomics, and single-nucleus RNA sequencing integration: exploring sphingolipids in MASH-HCC progression.\",\"authors\":\"Jing Zeng, Grayson Way, Nan Wu, Xixian Jiang, Yun-Ling Tai, Derrick Zhao, Lianyong Su, Qianhua Yan, Xuan Wang, Emily C Gurley, Phillip B Hylemon, Sayed Obaidullah Aseem, Arun J Sanyal, Jiangao Fan, Huiping Zhou\",\"doi\":\"10.1186/s13578-025-01362-5\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background & aims: </strong>Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses various conditions, ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. MASLD is a significant risk factor for hepatocellular carcinoma (HCC) and is rapidly becoming the primary cause of liver transplantation. Dysregulated sphingolipid metabolism has been linked to the development of MASH-HCC. However, detailed insight into the sphingolipid profiles and cell type-specific changes in key genes involved in sphingolipid metabolism remains limited and forms the primary focus of this study.</p><p><strong>Approaches & results: </strong>This study used the well-characterized diet-induced MASH-HCC mouse model (DIAMOND). Total RNA sequencing data, NanoString nCounter<sup>®</sup> Gene profiling, and single-nucleus RNA sequencing (snRNA-seq) GEO data (GSE225381) were used in characterizing gene regulation in MASH-HCC progression. Sphingolipids in the serum and liver were profiled using targeted lipidomics. RNA data analysis showed dysregulation of key genes involved in sphingolipid metabolism, including ceramide synthase 6 (Cers6), serine palmitoyltransferase long chain base subunit 2 (Sptlc2), sphingosine kinase 2 (SphK2), and sphingosine-1-phosphate receptor 1-3 (S1pr1-3) which paralleled significant changes in sphingolipid composition and levels in both serum and liver. Furthermore, TCGA-LIHC patient data were analyzed and potential prognostic genes for MASH-HCC were identified using univariate and multivariate Cox analysis. The multivariate Cox analysis underscored the prognostic significance of several genes related to sphingolipid metabolism, including CERS6, SPTLC2, and S1PR1.</p><p><strong>Conclusion: </strong>Our findings provided valuable insights into the role of sphingolipids in the progression of MASH to HCC. Specific serum and liver sphingolipid profiles may serve as valuable biomarkers for diagnosis and prognosis in MASH-HCC.</p>\",\"PeriodicalId\":49095,\"journal\":{\"name\":\"Cell and Bioscience\",\"volume\":\"15 1\",\"pages\":\"34\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2025-03-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11890728/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cell and Bioscience\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1186/s13578-025-01362-5\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cell and Bioscience","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1186/s13578-025-01362-5","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Transcriptomics, lipidomics, and single-nucleus RNA sequencing integration: exploring sphingolipids in MASH-HCC progression.
Background & aims: Metabolic dysfunction-associated steatotic liver disease (MASLD) encompasses various conditions, ranging from simple steatosis to metabolic dysfunction-associated steatohepatitis (MASH) and cirrhosis. MASLD is a significant risk factor for hepatocellular carcinoma (HCC) and is rapidly becoming the primary cause of liver transplantation. Dysregulated sphingolipid metabolism has been linked to the development of MASH-HCC. However, detailed insight into the sphingolipid profiles and cell type-specific changes in key genes involved in sphingolipid metabolism remains limited and forms the primary focus of this study.
Approaches & results: This study used the well-characterized diet-induced MASH-HCC mouse model (DIAMOND). Total RNA sequencing data, NanoString nCounter® Gene profiling, and single-nucleus RNA sequencing (snRNA-seq) GEO data (GSE225381) were used in characterizing gene regulation in MASH-HCC progression. Sphingolipids in the serum and liver were profiled using targeted lipidomics. RNA data analysis showed dysregulation of key genes involved in sphingolipid metabolism, including ceramide synthase 6 (Cers6), serine palmitoyltransferase long chain base subunit 2 (Sptlc2), sphingosine kinase 2 (SphK2), and sphingosine-1-phosphate receptor 1-3 (S1pr1-3) which paralleled significant changes in sphingolipid composition and levels in both serum and liver. Furthermore, TCGA-LIHC patient data were analyzed and potential prognostic genes for MASH-HCC were identified using univariate and multivariate Cox analysis. The multivariate Cox analysis underscored the prognostic significance of several genes related to sphingolipid metabolism, including CERS6, SPTLC2, and S1PR1.
Conclusion: Our findings provided valuable insights into the role of sphingolipids in the progression of MASH to HCC. Specific serum and liver sphingolipid profiles may serve as valuable biomarkers for diagnosis and prognosis in MASH-HCC.
期刊介绍：
Cell and Bioscience, the official journal of the Society of Chinese Bioscientists in America, is an open access, peer-reviewed journal that encompasses all areas of life science research.
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