Novel gene rearrangement leads to altered expression of Hornerin in sensitive and chemoresistant ovarian cancer
Background: Hornerin (HRNR) is part of the S100-fused protein family and has been linked to poorer prognosis in various cancers, though the mechanisms remain unclear. This study aimed to explore the role of HRNR in ovarian cancer. Methods: We conducted proteomic analysis (n = 252) and RNA sequencing...
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Elsevier
2025-11-01
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| Series: | Translational Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523325002268 |
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| author | Ghassan M. Saed Harvey Sharma Jenna Dabaja Asad Nawaz Ayesha Alvero Robert T. Morris Asma Basha Lucas Werner Toshima Z. Parris Khalil Helou |
| author_facet | Ghassan M. Saed Harvey Sharma Jenna Dabaja Asad Nawaz Ayesha Alvero Robert T. Morris Asma Basha Lucas Werner Toshima Z. Parris Khalil Helou |
| author_sort | Ghassan M. Saed |
| collection | DOAJ |
| description | Background: Hornerin (HRNR) is part of the S100-fused protein family and has been linked to poorer prognosis in various cancers, though the mechanisms remain unclear. This study aimed to explore the role of HRNR in ovarian cancer. Methods: We conducted proteomic analysis (n = 252) and RNA sequencing (n = 96) on primary ovarian carcinomas to evaluate HRNR expression across different histotypes, survival outcomes, and to identify genetic variants in the HRNR gene. We also assessed HRNR levels in both chemosensitive and chemoresistant ovarian cancer cell lines, as well as in serum samples at different disease stages. Results: Our findings revealed that HRNR levels were significantly higher in clear cell and mucinous ovarian carcinomas compared to high-grade serous carcinomas, with elevated expression associated with shorter survival. Additionally, HRNR levels increased in sera from late-stage patients compared to those in early stages. We identified several potentially harmful genetic variants in exon 3 of HRNR in patients with high-grade serous carcinoma, including a translocation of a 900 bp fragment from exon 3 to a region between exons 1 and 2. Chemoresistant ovarian cancer cells exhibited higher HRNR levels than chemosensitive cells. Silencing HRNR using siRNA markedly enhanced the cytotoxic effects on all tested ovarian cancer cells. Conclusions: HRNR plays a significant role in ovarian cancer with potential to serve as a prognostic marker. Additionally, targeting HRNR expression may offer therapeutic benefits, particularly for patients with chemoresistance or specific HRNR genetic variants, highlighting the need for further investigation in the management of ovarian cancer. Significance: Hornerin (HRNR) is linked to poor prognosis in various cancers, but its role in ovarian cancer has been underexplored. Our study shows that HRNR expression is significantly higher in clear cell and mucinous ovarian carcinomas compared to high-grade serous carcinomas, correlating with shorter survival. Elevated HRNR levels in late-stage patients suggest its potential as a prognostic marker. We also identified harmful genetic variants in HRNR, including a novel translocation, which may affect disease progression. Targeting HRNR could enhance chemotherapy effectiveness, particularly for patients with HRNR genetic variants, positioning it as a promising biomarker and therapeutic target in ovarian cancer. |
| format | Article |
| id | doaj-art-2c8ac8d24c9f40789d648dd5c7e9bd02 |
| institution | Kabale University |
| issn | 1936-5233 |
| language | English |
| publishDate | 2025-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj-art-2c8ac8d24c9f40789d648dd5c7e9bd022025-08-20T04:01:57ZengElsevierTranslational Oncology1936-52332025-11-016110249510.1016/j.tranon.2025.102495Novel gene rearrangement leads to altered expression of Hornerin in sensitive and chemoresistant ovarian cancerGhassan M. Saed0Harvey Sharma1Jenna Dabaja2Asad Nawaz3Ayesha Alvero4Robert T. Morris5Asma Basha6Lucas Werner7Toshima Z. Parris8Khalil Helou9Department of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Department of Gynecologic Oncology, Karmanos Cancer Institute, 48201, Detroit, MI, USA; Department of Obstetrics and Gynecology, University of Jordan School of Medicine, 226 Queen Rania Al Abdulla St, Amman 11942, Jordan; Corresponding author at: Departments of Obstetrics and Gynecology and Oncology, Karmanos Cancer Institute and Wayne State University School of Medicine, Detroit, MI 48202, USADepartment of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USADepartment of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USADepartment of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USADepartment of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USADepartment of Gynecologic Oncology, Karmanos Cancer Institute, 48201, Detroit, MI, USADepartment of Obstetrics and Gynecology, University of Jordan School of Medicine, 226 Queen Rania Al Abdulla St, Amman 11942, JordanDepartment of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Box 711 405 30, Gothenburg, Sweden; Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg 41685, SwedenDepartment of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Box 711 405 30, Gothenburg, Sweden; Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg 41685, SwedenDepartment of Oncology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Box 711 405 30, Gothenburg, Sweden; Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg 41685, SwedenBackground: Hornerin (HRNR) is part of the S100-fused protein family and has been linked to poorer prognosis in various cancers, though the mechanisms remain unclear. This study aimed to explore the role of HRNR in ovarian cancer. Methods: We conducted proteomic analysis (n = 252) and RNA sequencing (n = 96) on primary ovarian carcinomas to evaluate HRNR expression across different histotypes, survival outcomes, and to identify genetic variants in the HRNR gene. We also assessed HRNR levels in both chemosensitive and chemoresistant ovarian cancer cell lines, as well as in serum samples at different disease stages. Results: Our findings revealed that HRNR levels were significantly higher in clear cell and mucinous ovarian carcinomas compared to high-grade serous carcinomas, with elevated expression associated with shorter survival. Additionally, HRNR levels increased in sera from late-stage patients compared to those in early stages. We identified several potentially harmful genetic variants in exon 3 of HRNR in patients with high-grade serous carcinoma, including a translocation of a 900 bp fragment from exon 3 to a region between exons 1 and 2. Chemoresistant ovarian cancer cells exhibited higher HRNR levels than chemosensitive cells. Silencing HRNR using siRNA markedly enhanced the cytotoxic effects on all tested ovarian cancer cells. Conclusions: HRNR plays a significant role in ovarian cancer with potential to serve as a prognostic marker. Additionally, targeting HRNR expression may offer therapeutic benefits, particularly for patients with chemoresistance or specific HRNR genetic variants, highlighting the need for further investigation in the management of ovarian cancer. Significance: Hornerin (HRNR) is linked to poor prognosis in various cancers, but its role in ovarian cancer has been underexplored. Our study shows that HRNR expression is significantly higher in clear cell and mucinous ovarian carcinomas compared to high-grade serous carcinomas, correlating with shorter survival. Elevated HRNR levels in late-stage patients suggest its potential as a prognostic marker. We also identified harmful genetic variants in HRNR, including a novel translocation, which may affect disease progression. Targeting HRNR could enhance chemotherapy effectiveness, particularly for patients with HRNR genetic variants, positioning it as a promising biomarker and therapeutic target in ovarian cancer.http://www.sciencedirect.com/science/article/pii/S1936523325002268Gene rearrangementHornerin expressionChemoresistanceOvarian cancerTherapeutic markerHornerin mutations |
| spellingShingle | Ghassan M. Saed Harvey Sharma Jenna Dabaja Asad Nawaz Ayesha Alvero Robert T. Morris Asma Basha Lucas Werner Toshima Z. Parris Khalil Helou Novel gene rearrangement leads to altered expression of Hornerin in sensitive and chemoresistant ovarian cancer Translational Oncology Gene rearrangement Hornerin expression Chemoresistance Ovarian cancer Therapeutic marker Hornerin mutations |
| title | Novel gene rearrangement leads to altered expression of Hornerin in sensitive and chemoresistant ovarian cancer |
| title_full | Novel gene rearrangement leads to altered expression of Hornerin in sensitive and chemoresistant ovarian cancer |
| title_fullStr | Novel gene rearrangement leads to altered expression of Hornerin in sensitive and chemoresistant ovarian cancer |
| title_full_unstemmed | Novel gene rearrangement leads to altered expression of Hornerin in sensitive and chemoresistant ovarian cancer |
| title_short | Novel gene rearrangement leads to altered expression of Hornerin in sensitive and chemoresistant ovarian cancer |
| title_sort | novel gene rearrangement leads to altered expression of hornerin in sensitive and chemoresistant ovarian cancer |
| topic | Gene rearrangement Hornerin expression Chemoresistance Ovarian cancer Therapeutic marker Hornerin mutations |
| url | http://www.sciencedirect.com/science/article/pii/S1936523325002268 |
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