Identification of therapeutic targets and prognostic biomarkers among CC chemokines in the pancreatic adenocarcinoma microenvironment
Pancreatic adenocarcinoma (PAAD), one of the most aggressive and lethal malignant tumors, is correlated with increased morbidity and mortality. CC chemokines can modulate the infiltration of immune cells and affect the clinical outcome of cancer patients. However, the therapeutic potential and progn...
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| Format: | Article |
| Language: | English |
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KeAi Communications Co., Ltd.
2023-04-01
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| Series: | Gastroenterology & Endoscopy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2949752322000073 |
| _version_ | 1797235502452047872 |
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| author | Xinyuan Liu Qi Zhang Tao Mao Congcong Min Jing Guo Cuiping Zhang Zibin Tian Xiaoyu Li |
| author_facet | Xinyuan Liu Qi Zhang Tao Mao Congcong Min Jing Guo Cuiping Zhang Zibin Tian Xiaoyu Li |
| author_sort | Xinyuan Liu |
| collection | DOAJ |
| description | Pancreatic adenocarcinoma (PAAD), one of the most aggressive and lethal malignant tumors, is correlated with increased morbidity and mortality. CC chemokines can modulate the infiltration of immune cells and affect the clinical outcome of cancer patients. However, the therapeutic potential and prognostic value of CC chemokines in PAAD have not yet been elucidated. To do this, we comprehensively explore and analyze large amounts of data base on ONCOMINE, UALCAN, GEPIA2, LinkedOmics, Kaplan-Meier Plotter, cBioPortal, GeneMANIA, DAVID 6.8, TRRUST, TIMER, TISIDB, DGIdb, and TTD. We found the transcriptional levels of CCL5/7/13/15/18/19/20 in PAAD tissues were remarkably increased, whereas the transcriptional level of CCL17 was decreased. CCL20 expression had significantly been correlated with the tumor stage of PAAD patients. High expressions of CCL5, CCL7, CCL13, CCL18, and CCL20 were notably correlated with the prognosis of patients. Moreover, patients with CCL18 and CCL19 alterations showed a poor prognosis in both overall survival (OS) and disease-specific survival (DSS). Patients with CCL5 and CCL15 alterations also presented a poor prognosis in OS. The key transcription factors for CC chemokines are RELA and NF-κB1. The functions of the differentially expressed CC chemokines were mainly correlated the chemokine signaling pathway, cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, and so forth. We also discovered significant associations between the expression levels of CC chemokines and six infiltrating immune cells including, CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, and dendritic cells. The drug-gene interactions and related miRNAs of aberrant expression CC chemokines were also explored. Our study indicated the correlation between CC chemokines and PAAD and clarified the value of differentially expressed CC chemokines as potential therapeutic targets and prognostic markers for PAAD. |
| first_indexed | 2024-04-24T16:48:59Z |
| format | Article |
| id | doaj.art-eda5dc801a794853928272e67ea4d1fa |
| institution | Directory Open Access Journal |
| issn | 2949-7523 |
| language | English |
| last_indexed | 2024-04-24T16:48:59Z |
| publishDate | 2023-04-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Gastroenterology & Endoscopy |
| spelling | doaj.art-eda5dc801a794853928272e67ea4d1fa2024-03-29T05:51:55ZengKeAi Communications Co., Ltd.Gastroenterology & Endoscopy2949-75232023-04-011291101Identification of therapeutic targets and prognostic biomarkers among CC chemokines in the pancreatic adenocarcinoma microenvironmentXinyuan Liu0Qi Zhang1Tao Mao2Congcong Min3Jing Guo4Cuiping Zhang5Zibin Tian6Xiaoyu Li7Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaDepartment of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaCorresponding author.; Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, ChinaPancreatic adenocarcinoma (PAAD), one of the most aggressive and lethal malignant tumors, is correlated with increased morbidity and mortality. CC chemokines can modulate the infiltration of immune cells and affect the clinical outcome of cancer patients. However, the therapeutic potential and prognostic value of CC chemokines in PAAD have not yet been elucidated. To do this, we comprehensively explore and analyze large amounts of data base on ONCOMINE, UALCAN, GEPIA2, LinkedOmics, Kaplan-Meier Plotter, cBioPortal, GeneMANIA, DAVID 6.8, TRRUST, TIMER, TISIDB, DGIdb, and TTD. We found the transcriptional levels of CCL5/7/13/15/18/19/20 in PAAD tissues were remarkably increased, whereas the transcriptional level of CCL17 was decreased. CCL20 expression had significantly been correlated with the tumor stage of PAAD patients. High expressions of CCL5, CCL7, CCL13, CCL18, and CCL20 were notably correlated with the prognosis of patients. Moreover, patients with CCL18 and CCL19 alterations showed a poor prognosis in both overall survival (OS) and disease-specific survival (DSS). Patients with CCL5 and CCL15 alterations also presented a poor prognosis in OS. The key transcription factors for CC chemokines are RELA and NF-κB1. The functions of the differentially expressed CC chemokines were mainly correlated the chemokine signaling pathway, cytokine-cytokine receptor interaction, NF-kappa B signaling pathway, and so forth. We also discovered significant associations between the expression levels of CC chemokines and six infiltrating immune cells including, CD8+ T cells, CD4+ T cells, B cells, macrophages, neutrophils, and dendritic cells. The drug-gene interactions and related miRNAs of aberrant expression CC chemokines were also explored. Our study indicated the correlation between CC chemokines and PAAD and clarified the value of differentially expressed CC chemokines as potential therapeutic targets and prognostic markers for PAAD.http://www.sciencedirect.com/science/article/pii/S2949752322000073Pancreatic adenocarcinomaCC chemokinesPrognosisCytokinesTumor microenvironment |
| spellingShingle | Xinyuan Liu Qi Zhang Tao Mao Congcong Min Jing Guo Cuiping Zhang Zibin Tian Xiaoyu Li Identification of therapeutic targets and prognostic biomarkers among CC chemokines in the pancreatic adenocarcinoma microenvironment Gastroenterology & Endoscopy Pancreatic adenocarcinoma CC chemokines Prognosis Cytokines Tumor microenvironment |
| title | Identification of therapeutic targets and prognostic biomarkers among CC chemokines in the pancreatic adenocarcinoma microenvironment |
| title_full | Identification of therapeutic targets and prognostic biomarkers among CC chemokines in the pancreatic adenocarcinoma microenvironment |
| title_fullStr | Identification of therapeutic targets and prognostic biomarkers among CC chemokines in the pancreatic adenocarcinoma microenvironment |
| title_full_unstemmed | Identification of therapeutic targets and prognostic biomarkers among CC chemokines in the pancreatic adenocarcinoma microenvironment |
| title_short | Identification of therapeutic targets and prognostic biomarkers among CC chemokines in the pancreatic adenocarcinoma microenvironment |
| title_sort | identification of therapeutic targets and prognostic biomarkers among cc chemokines in the pancreatic adenocarcinoma microenvironment |
| topic | Pancreatic adenocarcinoma CC chemokines Prognosis Cytokines Tumor microenvironment |
| url | http://www.sciencedirect.com/science/article/pii/S2949752322000073 |
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