Huan Zhang, Paul Winter, Thomas Wartmann, Luca Simioni, Sara Al-Madhi, Aris Perrakis, Roland S Croner, Wenjie Shi, Quan Yu, Ulf D Kahlert
{"title":"开启临床洞察力:淋巴细胞特异性蛋白酪氨酸激酶候选靶点有望成为胰腺癌风险分层的治疗靶点。","authors":"Huan Zhang, Paul Winter, Thomas Wartmann, Luca Simioni, Sara Al-Madhi, Aris Perrakis, Roland S Croner, Wenjie Shi, Quan Yu, Ulf D Kahlert","doi":"10.1089/cbr.2024.0056","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Background:</i></b> Uncover the pivotal link between lymphocyte-specific protein tyrosine kinase (Lck)-related genes and clinical risk stratification in pancreatic cancer. <b><i>Methods:</i></b> This study identifies shared genes between differentially expressed genes (DEGs) and Lck-related genes in pancreatic cancer using a methodological framework rooted in The Cancer Genome Atlas database. Feature gene selection is accomplished and a signature model is constructed. Statistical significant clinical endpoints such as overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) were defined. <b><i>Results:</i></b> After performing random survival forest, Lasso regression, and multivariate Cox regression model, 7 trait genes out of 272 Lck-associated DEGs are selected to create a signature model that is independent of other clinical factors and can predict OS and DSS. It appears that high-risk patients have activated the TP53 signaling pathway and the cell cycle signaling pathway. <i>LAMA3</i> turned out to be the hub gene of the signature with high expression in pancreatic cancer. Patients with increased expression of <i>LAMA3</i> had a short OS, DSS, and PFI in comparison. The candidate competing endogenous RNA network of <i>LAMA3</i> turned out to be OPI5-AS1/hsa-miR-186-5p/<i>LAMA3</i> axis. <b><i>Conclusions:</i></b> A characteristic signature of seven Lck-related genes, especially <i>LAMA3</i>, has been shown to be a key factor in clinical risk stratification for pancreatic cancer.</p>","PeriodicalId":55277,"journal":{"name":"Cancer Biotherapy and Radiopharmaceuticals","volume":" ","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2024-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Unlocking Clinical Insights: Lymphocyte-Specific Protein Tyrosine Kinase Candidates as Promising Therapeutic Targets for Pancreatic Cancer Risk Stratification.\",\"authors\":\"Huan Zhang, Paul Winter, Thomas Wartmann, Luca Simioni, Sara Al-Madhi, Aris Perrakis, Roland S Croner, Wenjie Shi, Quan Yu, Ulf D Kahlert\",\"doi\":\"10.1089/cbr.2024.0056\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b><i>Background:</i></b> Uncover the pivotal link between lymphocyte-specific protein tyrosine kinase (Lck)-related genes and clinical risk stratification in pancreatic cancer. <b><i>Methods:</i></b> This study identifies shared genes between differentially expressed genes (DEGs) and Lck-related genes in pancreatic cancer using a methodological framework rooted in The Cancer Genome Atlas database. Feature gene selection is accomplished and a signature model is constructed. Statistical significant clinical endpoints such as overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) were defined. <b><i>Results:</i></b> After performing random survival forest, Lasso regression, and multivariate Cox regression model, 7 trait genes out of 272 Lck-associated DEGs are selected to create a signature model that is independent of other clinical factors and can predict OS and DSS. It appears that high-risk patients have activated the TP53 signaling pathway and the cell cycle signaling pathway. <i>LAMA3</i> turned out to be the hub gene of the signature with high expression in pancreatic cancer. Patients with increased expression of <i>LAMA3</i> had a short OS, DSS, and PFI in comparison. The candidate competing endogenous RNA network of <i>LAMA3</i> turned out to be OPI5-AS1/hsa-miR-186-5p/<i>LAMA3</i> axis. <b><i>Conclusions:</i></b> A characteristic signature of seven Lck-related genes, especially <i>LAMA3</i>, has been shown to be a key factor in clinical risk stratification for pancreatic cancer.</p>\",\"PeriodicalId\":55277,\"journal\":{\"name\":\"Cancer Biotherapy and Radiopharmaceuticals\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":2.4000,\"publicationDate\":\"2024-06-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Biotherapy and Radiopharmaceuticals\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1089/cbr.2024.0056\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Biotherapy and Radiopharmaceuticals","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/cbr.2024.0056","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Unlocking Clinical Insights: Lymphocyte-Specific Protein Tyrosine Kinase Candidates as Promising Therapeutic Targets for Pancreatic Cancer Risk Stratification.
Background: Uncover the pivotal link between lymphocyte-specific protein tyrosine kinase (Lck)-related genes and clinical risk stratification in pancreatic cancer. Methods: This study identifies shared genes between differentially expressed genes (DEGs) and Lck-related genes in pancreatic cancer using a methodological framework rooted in The Cancer Genome Atlas database. Feature gene selection is accomplished and a signature model is constructed. Statistical significant clinical endpoints such as overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI) were defined. Results: After performing random survival forest, Lasso regression, and multivariate Cox regression model, 7 trait genes out of 272 Lck-associated DEGs are selected to create a signature model that is independent of other clinical factors and can predict OS and DSS. It appears that high-risk patients have activated the TP53 signaling pathway and the cell cycle signaling pathway. LAMA3 turned out to be the hub gene of the signature with high expression in pancreatic cancer. Patients with increased expression of LAMA3 had a short OS, DSS, and PFI in comparison. The candidate competing endogenous RNA network of LAMA3 turned out to be OPI5-AS1/hsa-miR-186-5p/LAMA3 axis. Conclusions: A characteristic signature of seven Lck-related genes, especially LAMA3, has been shown to be a key factor in clinical risk stratification for pancreatic cancer.
期刊介绍:
Cancer Biotherapy and Radiopharmaceuticals is the established peer-reviewed journal, with over 25 years of cutting-edge content on innovative therapeutic investigations to ultimately improve cancer management. It is the only journal with the specific focus of cancer biotherapy and is inclusive of monoclonal antibodies, cytokine therapy, cancer gene therapy, cell-based therapies, and other forms of immunotherapies.
The Journal includes extensive reporting on advancements in radioimmunotherapy, and the use of radiopharmaceuticals and radiolabeled peptides for the development of new cancer treatments.