Revealing platelet-related subtypes and prognostic signature in pancreatic adenocarcinoma
Abstract Background Pancreatic adenocarcinoma (PDAC) is a malignant tumor with high heterogeneity and poor prognosis. In this study, we sought to identify the value of platelet-related genes in prognosis and heterogeneity of PDAC through multiple transcriptomic methods. Methods Based on datasets fro...
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| Format: | Article |
| Language: | English |
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BMC
2023-05-01
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| Series: | BMC Medical Genomics |
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| Online Access: | https://doi.org/10.1186/s12920-023-01530-x |
| _version_ | 1797822598205145088 |
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| author | Jian-Gang Zhao Yu-Jie Li Yong Wu Ke Zhang Lin-Jia Peng Hao Chen |
| author_facet | Jian-Gang Zhao Yu-Jie Li Yong Wu Ke Zhang Lin-Jia Peng Hao Chen |
| author_sort | Jian-Gang Zhao |
| collection | DOAJ |
| description | Abstract Background Pancreatic adenocarcinoma (PDAC) is a malignant tumor with high heterogeneity and poor prognosis. In this study, we sought to identify the value of platelet-related genes in prognosis and heterogeneity of PDAC through multiple transcriptomic methods. Methods Based on datasets from Gene Expression Omnibus and The Cancer Genome Atlas (TCGA), platelet-related genes were screened out, and the TCGA cohort (n = 171) was identified into two subtypes by unsupervised clustering. The platelet-related risk score model (PLRScore) was constructed by univariate Cox and LASSO regression, and the predictive ability was evaluated by Kaplan-Meier test and time-dependent receiver operating characteristic (ROC) curves. The results were validated in two other external validation sets, ICGC-CA (n = 140) and GSE62452 (n = 66). Furthermore, predictive nomogram containing clinical characteristics and PLRScore was established. In addition, we determined the possible correlation between PLRScore and immune infiltration and response of immunotherapy. Finally, we analyzed the heterogeneity of our signature in various types of cells using single-cell analysis. Results Platelet-related subtypes that have significant difference of overall survival and immune states (p < 0.05) were identified. PLRScore model based on four-gene signature (CEP55, LAMA3, CA12, SCN8A) was constructed to predict patient prognosis. The AUCs of training cohort were 0.697, 0.687 and 0.675 for 1-, 3-and 5-year, respectively. Further evaluation of the validation cohorts yielded similar results. In addition, PLRScore was associated with immune cell infiltration and immune checkpoint expression, and had promising ability to predict response to immunotherapy of PDAC. Conclusions In this study, the platelet-related subtypes were identified and the four-gene signature was constructed and validated. It may provide new insights into the therapeutic decision-making and molecular targets of PDAC. |
| first_indexed | 2024-03-13T10:11:27Z |
| format | Article |
| id | doaj.art-53a4ac44fad041d9801698d305df7b38 |
| institution | Directory Open Access Journal |
| issn | 1755-8794 |
| language | English |
| last_indexed | 2024-03-13T10:11:27Z |
| publishDate | 2023-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Medical Genomics |
| spelling | doaj.art-53a4ac44fad041d9801698d305df7b382023-05-21T11:29:34ZengBMCBMC Medical Genomics1755-87942023-05-0116111410.1186/s12920-023-01530-xRevealing platelet-related subtypes and prognostic signature in pancreatic adenocarcinomaJian-Gang Zhao0Yu-Jie Li1Yong Wu2Ke Zhang3Lin-Jia Peng4Hao Chen5Department of Oncology, Shaoxing Central HospitalDepartment of Oncology, Shanghai Medical College, Fudan UniversityDepartment of Oncology, The second affiliated Hospital of Anhui University of Traditional Chinese MedicineDepartment of Oncology, Shanghai Medical College, Fudan UniversityDepartment of Oncology, Shanghai Medical College, Fudan UniversityDepartment of Oncology, Shanghai Medical College, Fudan UniversityAbstract Background Pancreatic adenocarcinoma (PDAC) is a malignant tumor with high heterogeneity and poor prognosis. In this study, we sought to identify the value of platelet-related genes in prognosis and heterogeneity of PDAC through multiple transcriptomic methods. Methods Based on datasets from Gene Expression Omnibus and The Cancer Genome Atlas (TCGA), platelet-related genes were screened out, and the TCGA cohort (n = 171) was identified into two subtypes by unsupervised clustering. The platelet-related risk score model (PLRScore) was constructed by univariate Cox and LASSO regression, and the predictive ability was evaluated by Kaplan-Meier test and time-dependent receiver operating characteristic (ROC) curves. The results were validated in two other external validation sets, ICGC-CA (n = 140) and GSE62452 (n = 66). Furthermore, predictive nomogram containing clinical characteristics and PLRScore was established. In addition, we determined the possible correlation between PLRScore and immune infiltration and response of immunotherapy. Finally, we analyzed the heterogeneity of our signature in various types of cells using single-cell analysis. Results Platelet-related subtypes that have significant difference of overall survival and immune states (p < 0.05) were identified. PLRScore model based on four-gene signature (CEP55, LAMA3, CA12, SCN8A) was constructed to predict patient prognosis. The AUCs of training cohort were 0.697, 0.687 and 0.675 for 1-, 3-and 5-year, respectively. Further evaluation of the validation cohorts yielded similar results. In addition, PLRScore was associated with immune cell infiltration and immune checkpoint expression, and had promising ability to predict response to immunotherapy of PDAC. Conclusions In this study, the platelet-related subtypes were identified and the four-gene signature was constructed and validated. It may provide new insights into the therapeutic decision-making and molecular targets of PDAC.https://doi.org/10.1186/s12920-023-01530-xPancreatic adenocarcinomaPlateletMolecular classificationPrognostic signature, risk score |
| spellingShingle | Jian-Gang Zhao Yu-Jie Li Yong Wu Ke Zhang Lin-Jia Peng Hao Chen Revealing platelet-related subtypes and prognostic signature in pancreatic adenocarcinoma BMC Medical Genomics Pancreatic adenocarcinoma Platelet Molecular classification Prognostic signature, risk score |
| title | Revealing platelet-related subtypes and prognostic signature in pancreatic adenocarcinoma |
| title_full | Revealing platelet-related subtypes and prognostic signature in pancreatic adenocarcinoma |
| title_fullStr | Revealing platelet-related subtypes and prognostic signature in pancreatic adenocarcinoma |
| title_full_unstemmed | Revealing platelet-related subtypes and prognostic signature in pancreatic adenocarcinoma |
| title_short | Revealing platelet-related subtypes and prognostic signature in pancreatic adenocarcinoma |
| title_sort | revealing platelet related subtypes and prognostic signature in pancreatic adenocarcinoma |
| topic | Pancreatic adenocarcinoma Platelet Molecular classification Prognostic signature, risk score |
| url | https://doi.org/10.1186/s12920-023-01530-x |
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