The Association between TRP Channels Expression and Clinicopathological Characteristics of Patients with Pancreatic Adenocarcinoma
Pancreatic adenocarcinoma (PDAC) has low survival rates worldwide due to its tendency to be detected late and its characteristic desmoplastic reaction, which slows the use of targeted therapies. As such, the discovery of new connections between genes and the clinicopathological parameters contribute...
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| Language: | English |
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MDPI AG
2022-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/16/9045 |
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| author | Nicoleta-Raluca Chelaru Andrei Chiosa Andrei Sorop Andreea Spiridon Florentina Cojocaru Dan Domocos Dana Cucu Irinel Popescu Simona-Olimpia Dima |
| author_facet | Nicoleta-Raluca Chelaru Andrei Chiosa Andrei Sorop Andreea Spiridon Florentina Cojocaru Dan Domocos Dana Cucu Irinel Popescu Simona-Olimpia Dima |
| author_sort | Nicoleta-Raluca Chelaru |
| collection | DOAJ |
| description | Pancreatic adenocarcinoma (PDAC) has low survival rates worldwide due to its tendency to be detected late and its characteristic desmoplastic reaction, which slows the use of targeted therapies. As such, the discovery of new connections between genes and the clinicopathological parameters contribute to the search for new biomarkers or targets for therapy. Transient receptor potential (TRP) channels are promising tools for cancer therapy or markers for PDAC. Therefore, in this study, we selected several genes encoding TRP proteins previously reported in cellular models, namely, Transient Receptor Potential Cation Channel Subfamily V Member 6 (TRPV6), Transient receptor potential ankyrin 1 (TRPA1), and Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), as well as the TRPM8 Channel Associated Factor 1 (TCAF1) and TRPM8 Channel Associated Factor 2 (TCAF2) proteins, as regulatory factors. We analyzed the expression levels of tumors from patients enrolled in public datasets and confirmed the results with a validation cohort of PDAC patients enrolled in the Clinical Institute Fundeni, Romania. We found significantly higher expression levels of <i>TRPA1</i>, <i>TRPM8</i>, and <i>TCAF1/F2</i> in tumoral tissues compared to normal tissues, but lower expression levels of <i>TRPV6</i>, suggesting that TRP channels have either tumor-suppressive or oncogenic roles. The expression levels were correlated with the tumoral stages and are related to the genes involved in calcium homeostasis (<i>Calbindin 1</i> or <i>S100A4</i>) or to proteins participating in metastasis (<i>PTPN1</i>). We conclude that the selected TRP proteins provide new insights in the search for targets and biomarkers needed for therapeutic strategies for PDAC treatment. |
| first_indexed | 2024-03-09T04:20:17Z |
| format | Article |
| id | doaj.art-acce73ce361d405a85d61a82fc4a2798 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T04:20:17Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-acce73ce361d405a85d61a82fc4a27982023-12-03T13:48:13ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-08-012316904510.3390/ijms23169045The Association between TRP Channels Expression and Clinicopathological Characteristics of Patients with Pancreatic AdenocarcinomaNicoleta-Raluca Chelaru0Andrei Chiosa1Andrei Sorop2Andreea Spiridon3Florentina Cojocaru4Dan Domocos5Dana Cucu6Irinel Popescu7Simona-Olimpia Dima8Center of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, RomaniaCenter of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, RomaniaCenter of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, RomaniaCenter of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, RomaniaDepartment of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, RomaniaDepartment of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, RomaniaDepartment of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, Splaiul Independentei 91-95, 050095 Bucharest, RomaniaCenter of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, RomaniaCenter of Excellence in Translational Medicine, Fundeni Clinical Institute, 022328 Bucharest, RomaniaPancreatic adenocarcinoma (PDAC) has low survival rates worldwide due to its tendency to be detected late and its characteristic desmoplastic reaction, which slows the use of targeted therapies. As such, the discovery of new connections between genes and the clinicopathological parameters contribute to the search for new biomarkers or targets for therapy. Transient receptor potential (TRP) channels are promising tools for cancer therapy or markers for PDAC. Therefore, in this study, we selected several genes encoding TRP proteins previously reported in cellular models, namely, Transient Receptor Potential Cation Channel Subfamily V Member 6 (TRPV6), Transient receptor potential ankyrin 1 (TRPA1), and Transient receptor potential cation channel subfamily M (melastatin) member 8 (TRPM8), as well as the TRPM8 Channel Associated Factor 1 (TCAF1) and TRPM8 Channel Associated Factor 2 (TCAF2) proteins, as regulatory factors. We analyzed the expression levels of tumors from patients enrolled in public datasets and confirmed the results with a validation cohort of PDAC patients enrolled in the Clinical Institute Fundeni, Romania. We found significantly higher expression levels of <i>TRPA1</i>, <i>TRPM8</i>, and <i>TCAF1/F2</i> in tumoral tissues compared to normal tissues, but lower expression levels of <i>TRPV6</i>, suggesting that TRP channels have either tumor-suppressive or oncogenic roles. The expression levels were correlated with the tumoral stages and are related to the genes involved in calcium homeostasis (<i>Calbindin 1</i> or <i>S100A4</i>) or to proteins participating in metastasis (<i>PTPN1</i>). We conclude that the selected TRP proteins provide new insights in the search for targets and biomarkers needed for therapeutic strategies for PDAC treatment.https://www.mdpi.com/1422-0067/23/16/9045TRP channelsPDACTRPV6TRPM8TRPA1TCAF1 |
| spellingShingle | Nicoleta-Raluca Chelaru Andrei Chiosa Andrei Sorop Andreea Spiridon Florentina Cojocaru Dan Domocos Dana Cucu Irinel Popescu Simona-Olimpia Dima The Association between TRP Channels Expression and Clinicopathological Characteristics of Patients with Pancreatic Adenocarcinoma International Journal of Molecular Sciences TRP channels PDAC TRPV6 TRPM8 TRPA1 TCAF1 |
| title | The Association between TRP Channels Expression and Clinicopathological Characteristics of Patients with Pancreatic Adenocarcinoma |
| title_full | The Association between TRP Channels Expression and Clinicopathological Characteristics of Patients with Pancreatic Adenocarcinoma |
| title_fullStr | The Association between TRP Channels Expression and Clinicopathological Characteristics of Patients with Pancreatic Adenocarcinoma |
| title_full_unstemmed | The Association between TRP Channels Expression and Clinicopathological Characteristics of Patients with Pancreatic Adenocarcinoma |
| title_short | The Association between TRP Channels Expression and Clinicopathological Characteristics of Patients with Pancreatic Adenocarcinoma |
| title_sort | association between trp channels expression and clinicopathological characteristics of patients with pancreatic adenocarcinoma |
| topic | TRP channels PDAC TRPV6 TRPM8 TRPA1 TCAF1 |
| url | https://www.mdpi.com/1422-0067/23/16/9045 |
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