Deletions of <i>LPL</i> and <i>NKX3.1</i> in Prostate Cancer Progression: Game Changers or By-Standers in Tumor Evolution
The tumor suppressor gene <i>NKX3</i>.1 and the <i>LPL</i> gene are located in close proximity on chromosome 8, and their deletion has been reported in multiple studies. However, the significance of <i>LPL</i> loss may be misinterpreted due to its co-deletion with...
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MDPI AG
2025-05-01
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| Online Access: | https://www.mdpi.com/2218-273X/15/6/758 |
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| author | Tereza Vodičková Mária Wozniaková Vladimír Židlík Jana Žmolíková Jana Dvořáčková Adéla Kondé Jana Schwarzerová Michal Grepl Jan Bouchal |
| author_facet | Tereza Vodičková Mária Wozniaková Vladimír Židlík Jana Žmolíková Jana Dvořáčková Adéla Kondé Jana Schwarzerová Michal Grepl Jan Bouchal |
| author_sort | Tereza Vodičková |
| collection | DOAJ |
| description | The tumor suppressor gene <i>NKX3</i>.1 and the <i>LPL</i> gene are located in close proximity on chromosome 8, and their deletion has been reported in multiple studies. However, the significance of <i>LPL</i> loss may be misinterpreted due to its co-deletion with <i>NKX3.1</i>, a well-established event in prostate carcinogenesis. This study investigates whether <i>LPL</i> deletion represents a biologically relevant event or occurs merely as a bystander to <i>NKX3.1</i> loss. We analyzed 28 formalin-fixed paraffin-embedded prostate cancer samples with confirmed <i>LPL</i> deletion and 28 without. Immunohistochemical staining was performed, and previously published whole-genome sequencing data from 103 prostate cancer patients were reanalyzed. Deletion of the 8p21.3 region was associated with higher Gleason grade groups. While NKX3.1 expression was significantly reduced in prostate cancer compared to benign prostatic hyperplasia, LPL protein expression showed no significant difference between cancerous and benign tissue, nor was it affected by the 8p21.3 deletion status. Copy number analysis confirmed the co-deletion of <i>NKX3.1</i> and <i>LPL</i> in 54 patients. Notably, <i>NKX3.1</i> loss without accompanying <i>LPL</i> deletion was observed in eight additional cases. These findings suggest that <i>LPL</i> deletion is a passenger event secondary to <i>NKX3.1</i> loss and underscore the importance of cautious interpretation of cytogenetic findings involving the <i>LPL</i> locus. |
| format | Article |
| id | doaj-art-5cde364c99224ac3a68bc02ccc738b44 |
| institution | Kabale University |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj-art-5cde364c99224ac3a68bc02ccc738b442025-08-20T03:26:20ZengMDPI AGBiomolecules2218-273X2025-05-0115675810.3390/biom15060758Deletions of <i>LPL</i> and <i>NKX3.1</i> in Prostate Cancer Progression: Game Changers or By-Standers in Tumor EvolutionTereza Vodičková0Mária Wozniaková1Vladimír Židlík2Jana Žmolíková3Jana Dvořáčková4Adéla Kondé5Jana Schwarzerová6Michal Grepl7Jan Bouchal8Institute of Clinical and Molecular Pathology and Medical Genetics, University Hospital Ostrava and Medical Faculty Ostrava, 703 52 Ostrava, Czech RepublicInstitute of Clinical and Molecular Pathology and Medical Genetics, University Hospital Ostrava and Medical Faculty Ostrava, 703 52 Ostrava, Czech RepublicInstitute of Clinical and Molecular Pathology and Medical Genetics, University Hospital Ostrava and Medical Faculty Ostrava, 703 52 Ostrava, Czech RepublicEUC Laboratories CGB, a.s., 703 00 Ostrava, Czech RepublicEUC Laboratories CGB, a.s., 703 00 Ostrava, Czech RepublicDepartment of Applied Mathematics, Faculty of Electrical Engineering and Computer Science, VSB—Technical University of Ostrava, 708 00 Ostrava, Czech RepublicInstitute of Clinical and Molecular Pathology and Medical Genetics, University Hospital Ostrava and Medical Faculty Ostrava, 703 52 Ostrava, Czech RepublicDepartment of Urology, University Hospital Ostrava, 703 52 Ostrava, Czech RepublicDepartment of Clinical and Molecular Pathology, Institute of Molecular and Translational Medicine, Palacky University and University Hospital Olomouc, 779 00 Olomouc, Czech RepublicThe tumor suppressor gene <i>NKX3</i>.1 and the <i>LPL</i> gene are located in close proximity on chromosome 8, and their deletion has been reported in multiple studies. However, the significance of <i>LPL</i> loss may be misinterpreted due to its co-deletion with <i>NKX3.1</i>, a well-established event in prostate carcinogenesis. This study investigates whether <i>LPL</i> deletion represents a biologically relevant event or occurs merely as a bystander to <i>NKX3.1</i> loss. We analyzed 28 formalin-fixed paraffin-embedded prostate cancer samples with confirmed <i>LPL</i> deletion and 28 without. Immunohistochemical staining was performed, and previously published whole-genome sequencing data from 103 prostate cancer patients were reanalyzed. Deletion of the 8p21.3 region was associated with higher Gleason grade groups. While NKX3.1 expression was significantly reduced in prostate cancer compared to benign prostatic hyperplasia, LPL protein expression showed no significant difference between cancerous and benign tissue, nor was it affected by the 8p21.3 deletion status. Copy number analysis confirmed the co-deletion of <i>NKX3.1</i> and <i>LPL</i> in 54 patients. Notably, <i>NKX3.1</i> loss without accompanying <i>LPL</i> deletion was observed in eight additional cases. These findings suggest that <i>LPL</i> deletion is a passenger event secondary to <i>NKX3.1</i> loss and underscore the importance of cautious interpretation of cytogenetic findings involving the <i>LPL</i> locus.https://www.mdpi.com/2218-273X/15/6/758prostate cancerLPLNKX3.1immunohistochemistryFISHwhole-genome sequencing |
| spellingShingle | Tereza Vodičková Mária Wozniaková Vladimír Židlík Jana Žmolíková Jana Dvořáčková Adéla Kondé Jana Schwarzerová Michal Grepl Jan Bouchal Deletions of <i>LPL</i> and <i>NKX3.1</i> in Prostate Cancer Progression: Game Changers or By-Standers in Tumor Evolution Biomolecules prostate cancer LPL NKX3.1 immunohistochemistry FISH whole-genome sequencing |
| title | Deletions of <i>LPL</i> and <i>NKX3.1</i> in Prostate Cancer Progression: Game Changers or By-Standers in Tumor Evolution |
| title_full | Deletions of <i>LPL</i> and <i>NKX3.1</i> in Prostate Cancer Progression: Game Changers or By-Standers in Tumor Evolution |
| title_fullStr | Deletions of <i>LPL</i> and <i>NKX3.1</i> in Prostate Cancer Progression: Game Changers or By-Standers in Tumor Evolution |
| title_full_unstemmed | Deletions of <i>LPL</i> and <i>NKX3.1</i> in Prostate Cancer Progression: Game Changers or By-Standers in Tumor Evolution |
| title_short | Deletions of <i>LPL</i> and <i>NKX3.1</i> in Prostate Cancer Progression: Game Changers or By-Standers in Tumor Evolution |
| title_sort | deletions of i lpl i and i nkx3 1 i in prostate cancer progression game changers or by standers in tumor evolution |
| topic | prostate cancer LPL NKX3.1 immunohistochemistry FISH whole-genome sequencing |
| url | https://www.mdpi.com/2218-273X/15/6/758 |
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