Genomic insights and prognostic significance of novel biomarkers in pancreatic ductal adenocarcinoma: A comprehensive analysis
Pancreatic ductal adenocarcinoma (PDAC) is a highly prevalent digestive system malignancy, with a significant impact on public health, especially in the elderly population. The advent of the Human Genome Project has opened new avenues for precision medicine, allowing researchers to explore genetic m...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-03-01
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| Series: | Biochemistry and Biophysics Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405580823001619 |
| _version_ | 1797317132171608064 |
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| author | Yuling Chen Anle Huang Yuanjie Bi Wei Wei Yongsheng Huang Yuanchun Ye |
| author_facet | Yuling Chen Anle Huang Yuanjie Bi Wei Wei Yongsheng Huang Yuanchun Ye |
| author_sort | Yuling Chen |
| collection | DOAJ |
| description | Pancreatic ductal adenocarcinoma (PDAC) is a highly prevalent digestive system malignancy, with a significant impact on public health, especially in the elderly population. The advent of the Human Genome Project has opened new avenues for precision medicine, allowing researchers to explore genetic markers and molecular targets for cancer diagnosis and treatment. Despite significant advances in genomic research, early diagnosis of pancreatic cancer remains elusive due to the lack of highly sensitive and specific markers. Therefore, there is a need for in-depth research to identify more precise and reliable diagnostic markers for pancreatic cancer. In this study, we utilized a combination of public databases from different sources to meticulously screen genes associated with prognosis in pancreatic cancer. We used gene differential analysis, univariate cox regression analysis, least absolute selection and shrinkage operator (LASSO) regression, and multivariate cox regression analysis to identify genes associated with prognosis. Subsequently, we constructed a scoring system, validated its validity using survival analysis and ROC analysis, and further confirmed its reliability by nomogram and decision curve analysis (DCA). We evaluated the diagnostic value of this scoring system for pancreatic cancer prognosis and validated the function of the genes using single cell data analysis. Our analysis identifies six genes, including GABRA3, IL20RB, CDK1, GPR87, TTYH3, and KCNA2, that were strongly associated with PDAC prognosis. Clinical prognostic models based on these genes showed strong predictive power not only in the training set but also in external datasets. Functional enrichment analysis revealed significant differences between high- and low-risk groups mainly in immune-related functions. Additionally, we explored the potential of the risk score as a marker for immunotherapy response and identified key factors within the tumor microenvironment. The single-cell RNA sequencing analysis further enriched our understanding of cell clusters and six hub genes expressions. This comprehensive investigation provides valuable insights into pancreatic PDAC and its intricate immune landscape. The identified genes and their functional significance underscore the importance of continued research into improving diagnosis and treatment strategies for PDAC. |
| first_indexed | 2024-03-08T03:30:25Z |
| format | Article |
| id | doaj.art-8acb57c9a424458d9d9f6f4bbf0542d4 |
| institution | Directory Open Access Journal |
| issn | 2405-5808 |
| language | English |
| last_indexed | 2024-03-08T03:30:25Z |
| publishDate | 2024-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biochemistry and Biophysics Reports |
| spelling | doaj.art-8acb57c9a424458d9d9f6f4bbf0542d42024-02-11T05:11:10ZengElsevierBiochemistry and Biophysics Reports2405-58082024-03-0137101580Genomic insights and prognostic significance of novel biomarkers in pancreatic ductal adenocarcinoma: A comprehensive analysisYuling Chen0Anle Huang1Yuanjie Bi2Wei Wei3Yongsheng Huang4Yuanchun Ye5Department of Rheumatology and Immunology, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, ChinaDepartment of Gastrointestinal Oncology Surgery, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, Fujian, China, 361001School of Science, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, 518107, ChinaDepartment of Emergency, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong Province, ChinaSchool of Science, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, 518107, China; Corresponding author.School of Science, Shenzhen Campus of Sun Yat-Sen University, Shenzhen, 518107, China; Shenzhen Bay Laboratory, Shenzhen, Guangdong Province, China; Department of Hematology Oncology and Tumor Immunity, Benjamin Franklin Campus, Charité–Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany; Corresponding author. School of Science, Sun Yat-Sen University, Shenzhen 518107, China.Pancreatic ductal adenocarcinoma (PDAC) is a highly prevalent digestive system malignancy, with a significant impact on public health, especially in the elderly population. The advent of the Human Genome Project has opened new avenues for precision medicine, allowing researchers to explore genetic markers and molecular targets for cancer diagnosis and treatment. Despite significant advances in genomic research, early diagnosis of pancreatic cancer remains elusive due to the lack of highly sensitive and specific markers. Therefore, there is a need for in-depth research to identify more precise and reliable diagnostic markers for pancreatic cancer. In this study, we utilized a combination of public databases from different sources to meticulously screen genes associated with prognosis in pancreatic cancer. We used gene differential analysis, univariate cox regression analysis, least absolute selection and shrinkage operator (LASSO) regression, and multivariate cox regression analysis to identify genes associated with prognosis. Subsequently, we constructed a scoring system, validated its validity using survival analysis and ROC analysis, and further confirmed its reliability by nomogram and decision curve analysis (DCA). We evaluated the diagnostic value of this scoring system for pancreatic cancer prognosis and validated the function of the genes using single cell data analysis. Our analysis identifies six genes, including GABRA3, IL20RB, CDK1, GPR87, TTYH3, and KCNA2, that were strongly associated with PDAC prognosis. Clinical prognostic models based on these genes showed strong predictive power not only in the training set but also in external datasets. Functional enrichment analysis revealed significant differences between high- and low-risk groups mainly in immune-related functions. Additionally, we explored the potential of the risk score as a marker for immunotherapy response and identified key factors within the tumor microenvironment. The single-cell RNA sequencing analysis further enriched our understanding of cell clusters and six hub genes expressions. This comprehensive investigation provides valuable insights into pancreatic PDAC and its intricate immune landscape. The identified genes and their functional significance underscore the importance of continued research into improving diagnosis and treatment strategies for PDAC.http://www.sciencedirect.com/science/article/pii/S2405580823001619Pancreatic ductal adenocarcinomaPrognostic signatureRNA-seq analysis |
| spellingShingle | Yuling Chen Anle Huang Yuanjie Bi Wei Wei Yongsheng Huang Yuanchun Ye Genomic insights and prognostic significance of novel biomarkers in pancreatic ductal adenocarcinoma: A comprehensive analysis Biochemistry and Biophysics Reports Pancreatic ductal adenocarcinoma Prognostic signature RNA-seq analysis |
| title | Genomic insights and prognostic significance of novel biomarkers in pancreatic ductal adenocarcinoma: A comprehensive analysis |
| title_full | Genomic insights and prognostic significance of novel biomarkers in pancreatic ductal adenocarcinoma: A comprehensive analysis |
| title_fullStr | Genomic insights and prognostic significance of novel biomarkers in pancreatic ductal adenocarcinoma: A comprehensive analysis |
| title_full_unstemmed | Genomic insights and prognostic significance of novel biomarkers in pancreatic ductal adenocarcinoma: A comprehensive analysis |
| title_short | Genomic insights and prognostic significance of novel biomarkers in pancreatic ductal adenocarcinoma: A comprehensive analysis |
| title_sort | genomic insights and prognostic significance of novel biomarkers in pancreatic ductal adenocarcinoma a comprehensive analysis |
| topic | Pancreatic ductal adenocarcinoma Prognostic signature RNA-seq analysis |
| url | http://www.sciencedirect.com/science/article/pii/S2405580823001619 |
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