Molecular subtyping based on TRP family and prognostic assessment for TRP-associated lncRNAs in pancreatic adenocarcinoma
Abstract Background Transient receptor potential (TRP) channels have high permeability to Ca2+ ions because they are non-selective ion channels. TRP channels have been implicated in tumor onset and progression, proliferation, and migration in recent years. However, the prognostic value of genes rela...
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | BMC Gastroenterology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12876-022-02552-y |
| _version_ | 1817970294302703616 |
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| author | Lincheng Li Zhaohui Xiao Pengyi He Wenbo Zou Zhaoda Deng Gong Zhang Rong Liu |
| author_facet | Lincheng Li Zhaohui Xiao Pengyi He Wenbo Zou Zhaoda Deng Gong Zhang Rong Liu |
| author_sort | Lincheng Li |
| collection | DOAJ |
| description | Abstract Background Transient receptor potential (TRP) channels have high permeability to Ca2+ ions because they are non-selective ion channels. TRP channels have been implicated in tumor onset and progression, proliferation, and migration in recent years. However, the prognostic value of genes related to TRP and their specific mechanism in pancreatic adenocarcinoma (PAAD) are yet to be understood. Methods Public databases such as TCGA and GEO were used to retrieve data on gene expression and clinical information of patients with pancreatic adenocarcinoma for our study. ConsensusClusterPlus package was used for unsupervised clustering analysis. The microenvironment cell population (MCP)-counter approach was employed to measure the immune cells infiltration status. The Pearson correlation was performed to identify TRP-associated lncRNAs. Results Initially, we separated PAAD patients into three clusters depending on TRP-related genes, and of the three clusters, cluster B showed the least immune cell infiltration, which was correlated with poor prognosis. Moreover, GSVA enrichment analysis further revealed that cluster A was subjected to a considerable enrichment in carcinogenic signaling pathways, whereas cluster C was enriched in immune-related pathways. Then, using TRP-associated lncRNAs as a starting point, we constructed a prognostic risk model for PAAD patients that could efficiently predict their prognosis. Further, GSEA revealed that cancer-related pathways, for instance, the cell cycle, p53 signaling pathway, etc. were considerably enriched in the high-risk group. In addition, we looked into the link between the prognostic model and the immunological microenvironment. Lower cytotoxic lymphocytes, NK cells, CD8 T cells, and endothelial cells infiltration were found to be associated with high risk using the MCP-counter algorithm. The expression of CD274, POLE2, MCM6, and LOXL2 was also found to be higher in the high-risk group. TMB was also considerably greater in high-risk individuals, indicating that immune checkpoint inhibitors (ICIs) therapy may benefit them more. Lastly, qRT-PCR further confirmed the differential expression of these prognostic TRP-associated lncRNAs, indicating that these lncRNAs play an imperative role in PAAD tumorigenesis. Conclusion TRP family genes may represent a new class of candidate molecular markers of the occurrence and progression of PAAD. Risk models based on TRP-associated lncRNAs could provide important new references for immunotargeted therapy of pancreatic adenocarcinoma. |
| first_indexed | 2024-04-13T20:32:16Z |
| format | Article |
| id | doaj.art-59fb423376db4ea4b5915ee9690b66a4 |
| institution | Directory Open Access Journal |
| issn | 1471-230X |
| language | English |
| last_indexed | 2024-04-13T20:32:16Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Gastroenterology |
| spelling | doaj.art-59fb423376db4ea4b5915ee9690b66a42022-12-22T02:31:08ZengBMCBMC Gastroenterology1471-230X2022-11-0122111410.1186/s12876-022-02552-yMolecular subtyping based on TRP family and prognostic assessment for TRP-associated lncRNAs in pancreatic adenocarcinomaLincheng Li0Zhaohui Xiao1Pengyi He2Wenbo Zou3Zhaoda Deng4Gong Zhang5Rong Liu6Medical School of Chinese PLAFaculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center, Chinese PLA General HospitalMedical School of Chinese PLADepartment of General Surgery, No.924 Hospital of PLA Joint Logistic Support ForceMedical School of Chinese PLAMedical School of Chinese PLAFaculty of Hepato-Pancreato-Biliary Surgery, the First Medical Center, Chinese PLA General HospitalAbstract Background Transient receptor potential (TRP) channels have high permeability to Ca2+ ions because they are non-selective ion channels. TRP channels have been implicated in tumor onset and progression, proliferation, and migration in recent years. However, the prognostic value of genes related to TRP and their specific mechanism in pancreatic adenocarcinoma (PAAD) are yet to be understood. Methods Public databases such as TCGA and GEO were used to retrieve data on gene expression and clinical information of patients with pancreatic adenocarcinoma for our study. ConsensusClusterPlus package was used for unsupervised clustering analysis. The microenvironment cell population (MCP)-counter approach was employed to measure the immune cells infiltration status. The Pearson correlation was performed to identify TRP-associated lncRNAs. Results Initially, we separated PAAD patients into three clusters depending on TRP-related genes, and of the three clusters, cluster B showed the least immune cell infiltration, which was correlated with poor prognosis. Moreover, GSVA enrichment analysis further revealed that cluster A was subjected to a considerable enrichment in carcinogenic signaling pathways, whereas cluster C was enriched in immune-related pathways. Then, using TRP-associated lncRNAs as a starting point, we constructed a prognostic risk model for PAAD patients that could efficiently predict their prognosis. Further, GSEA revealed that cancer-related pathways, for instance, the cell cycle, p53 signaling pathway, etc. were considerably enriched in the high-risk group. In addition, we looked into the link between the prognostic model and the immunological microenvironment. Lower cytotoxic lymphocytes, NK cells, CD8 T cells, and endothelial cells infiltration were found to be associated with high risk using the MCP-counter algorithm. The expression of CD274, POLE2, MCM6, and LOXL2 was also found to be higher in the high-risk group. TMB was also considerably greater in high-risk individuals, indicating that immune checkpoint inhibitors (ICIs) therapy may benefit them more. Lastly, qRT-PCR further confirmed the differential expression of these prognostic TRP-associated lncRNAs, indicating that these lncRNAs play an imperative role in PAAD tumorigenesis. Conclusion TRP family genes may represent a new class of candidate molecular markers of the occurrence and progression of PAAD. Risk models based on TRP-associated lncRNAs could provide important new references for immunotargeted therapy of pancreatic adenocarcinoma.https://doi.org/10.1186/s12876-022-02552-yTRP familylncRNAImmune microenvironmentPancreatic adenocarcinoma |
| spellingShingle | Lincheng Li Zhaohui Xiao Pengyi He Wenbo Zou Zhaoda Deng Gong Zhang Rong Liu Molecular subtyping based on TRP family and prognostic assessment for TRP-associated lncRNAs in pancreatic adenocarcinoma BMC Gastroenterology TRP family lncRNA Immune microenvironment Pancreatic adenocarcinoma |
| title | Molecular subtyping based on TRP family and prognostic assessment for TRP-associated lncRNAs in pancreatic adenocarcinoma |
| title_full | Molecular subtyping based on TRP family and prognostic assessment for TRP-associated lncRNAs in pancreatic adenocarcinoma |
| title_fullStr | Molecular subtyping based on TRP family and prognostic assessment for TRP-associated lncRNAs in pancreatic adenocarcinoma |
| title_full_unstemmed | Molecular subtyping based on TRP family and prognostic assessment for TRP-associated lncRNAs in pancreatic adenocarcinoma |
| title_short | Molecular subtyping based on TRP family and prognostic assessment for TRP-associated lncRNAs in pancreatic adenocarcinoma |
| title_sort | molecular subtyping based on trp family and prognostic assessment for trp associated lncrnas in pancreatic adenocarcinoma |
| topic | TRP family lncRNA Immune microenvironment Pancreatic adenocarcinoma |
| url | https://doi.org/10.1186/s12876-022-02552-y |
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