Prognostic Value, Immune Signature, and Molecular Mechanisms of the PHLDA Family in Pancreatic Adenocarcinoma
Background: Increasing evidence supports the belief that the pleckstrin homology domain family A (PHLDA) family is associated with the development of a variety of cancers. However, the function of the PHLDA family members in PAAD is still unclear. Methods: Comprehensive bioinformatic analyses using...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/18/10316 |
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| author | Yunjie Duan Yongxing Du Zongting Gu Xiaohao Zheng Chengfeng Wang |
| author_facet | Yunjie Duan Yongxing Du Zongting Gu Xiaohao Zheng Chengfeng Wang |
| author_sort | Yunjie Duan |
| collection | DOAJ |
| description | Background: Increasing evidence supports the belief that the pleckstrin homology domain family A (PHLDA) family is associated with the development of a variety of cancers. However, the function of the PHLDA family members in PAAD is still unclear. Methods: Comprehensive bioinformatic analyses using R (version 3.6.3), Cytoscape (version 3.9.1), UALCAN, etc., were performed to study the clinicopathological characteristics, prognostic value, immune features, and functional mechanisms of the PHLDA family members in PAAD. Results: The PHLDA family members showed significantly elevated expression in PAAD compared with paracancerous or normal tissues. Their high expression or amplification were significantly correlated with worse clinicopathological characteristics and prognosis in PAAD patients. In addition, the role of the PHLDA family members in the immune regulation is diverse and complex. Mechanistically, TP53 mutations were significantly associated with the promoter methylation and expression levels of the PHLDA family members, which were activated in multiple oncogenic pathways, including the EMT, RAS/MAPK, and TSC/mTOR pathways. Moreover, we found that their expression levels were significantly correlated with the sensitivity of multiple traditional chemotherapeutic drugs and novel targeted MEK1/2 inhibitors. Conclusion: The PHLDA family members play an oncogenic role in the development of PAAD and might serve as new biomarkers or therapeutic targets. |
| first_indexed | 2024-03-09T23:49:10Z |
| format | Article |
| id | doaj.art-e8ae7fa950014a98b7115c617b83cd8b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:49:10Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e8ae7fa950014a98b7115c617b83cd8b2023-11-23T16:39:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123181031610.3390/ijms231810316Prognostic Value, Immune Signature, and Molecular Mechanisms of the PHLDA Family in Pancreatic AdenocarcinomaYunjie Duan0Yongxing Du1Zongting Gu2Xiaohao Zheng3Chengfeng Wang4State Key Lab of Molecular Oncology and Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, ChinaState Key Lab of Molecular Oncology and Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, ChinaDepartment of Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People’s Hospital, Hangzhou Medical College, Hangzhou 310000, ChinaState Key Lab of Molecular Oncology and Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, ChinaState Key Lab of Molecular Oncology and Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, ChinaBackground: Increasing evidence supports the belief that the pleckstrin homology domain family A (PHLDA) family is associated with the development of a variety of cancers. However, the function of the PHLDA family members in PAAD is still unclear. Methods: Comprehensive bioinformatic analyses using R (version 3.6.3), Cytoscape (version 3.9.1), UALCAN, etc., were performed to study the clinicopathological characteristics, prognostic value, immune features, and functional mechanisms of the PHLDA family members in PAAD. Results: The PHLDA family members showed significantly elevated expression in PAAD compared with paracancerous or normal tissues. Their high expression or amplification were significantly correlated with worse clinicopathological characteristics and prognosis in PAAD patients. In addition, the role of the PHLDA family members in the immune regulation is diverse and complex. Mechanistically, TP53 mutations were significantly associated with the promoter methylation and expression levels of the PHLDA family members, which were activated in multiple oncogenic pathways, including the EMT, RAS/MAPK, and TSC/mTOR pathways. Moreover, we found that their expression levels were significantly correlated with the sensitivity of multiple traditional chemotherapeutic drugs and novel targeted MEK1/2 inhibitors. Conclusion: The PHLDA family members play an oncogenic role in the development of PAAD and might serve as new biomarkers or therapeutic targets.https://www.mdpi.com/1422-0067/23/18/10316pancreatic adenocarcinomaPHLDA familyTP53biomarkersprognosisimmune infiltration |
| spellingShingle | Yunjie Duan Yongxing Du Zongting Gu Xiaohao Zheng Chengfeng Wang Prognostic Value, Immune Signature, and Molecular Mechanisms of the PHLDA Family in Pancreatic Adenocarcinoma International Journal of Molecular Sciences pancreatic adenocarcinoma PHLDA family TP53 biomarkers prognosis immune infiltration |
| title | Prognostic Value, Immune Signature, and Molecular Mechanisms of the PHLDA Family in Pancreatic Adenocarcinoma |
| title_full | Prognostic Value, Immune Signature, and Molecular Mechanisms of the PHLDA Family in Pancreatic Adenocarcinoma |
| title_fullStr | Prognostic Value, Immune Signature, and Molecular Mechanisms of the PHLDA Family in Pancreatic Adenocarcinoma |
| title_full_unstemmed | Prognostic Value, Immune Signature, and Molecular Mechanisms of the PHLDA Family in Pancreatic Adenocarcinoma |
| title_short | Prognostic Value, Immune Signature, and Molecular Mechanisms of the PHLDA Family in Pancreatic Adenocarcinoma |
| title_sort | prognostic value immune signature and molecular mechanisms of the phlda family in pancreatic adenocarcinoma |
| topic | pancreatic adenocarcinoma PHLDA family TP53 biomarkers prognosis immune infiltration |
| url | https://www.mdpi.com/1422-0067/23/18/10316 |
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