Attenuated titin protein expression is associated with advanced stages of ovarian cancer
This study explores the role of titin, a giant muscle protein, in the progression of epithelial ovarian cancer (EOC). We examined titin levels in tissues and sera from EOC patients across stages I–IV and in chemoresistant EOC cells. Tissue samples underwent immunohistochemistry, and serum titin leve...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-03-01
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| Series: | Molecular Therapy: Oncology |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950329925000013 |
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| author | Harvey Sharma Jaskaran Aujla Asad Nawaz Thabet Khasawneh Ayesha Alvero Robert T. Morris Asma Basha Laila Tutunji Toshima Z. Parris Khalil Helou Ghassan M. Saed |
| author_facet | Harvey Sharma Jaskaran Aujla Asad Nawaz Thabet Khasawneh Ayesha Alvero Robert T. Morris Asma Basha Laila Tutunji Toshima Z. Parris Khalil Helou Ghassan M. Saed |
| author_sort | Harvey Sharma |
| collection | DOAJ |
| description | This study explores the role of titin, a giant muscle protein, in the progression of epithelial ovarian cancer (EOC). We examined titin levels in tissues and sera from EOC patients across stages I–IV and in chemoresistant EOC cells. Tissue samples underwent immunohistochemistry, and serum titin levels were measured using ELISA. Quantitative real-time PCR analyzed titin mRNA in cell lines, including chemosensitive, chemoresistant, and normal ovarian cells. Notably, elevated titin levels were detected in 90.9% of stage I tissues compared to only 14.3% of stage III and IV tissues. Serum titin levels were consistently decreased across all stages relative to healthy controls, with a gradual decrease in expression from stages I to IV. Additionally, titin levels were significantly higher in normal ovarian epithelial cells compared to both chemosensitive and chemoresistant EOC cells, albeit significantly higher in chemosensitive than chemoresistant cells. These findings suggest the possible role of decreased titin levels as a marker for therapeutic intervention, particularly in advanced-stage and chemoresistant EOC. Further elucidation of the mechanisms underlying attenuated titin expression holds promise for advancing our understanding of ovarian cancer pathogenesis. |
| format | Article |
| id | doaj-art-4e8a6e6eb7294730a034e2eec3dacbfa |
| institution | Kabale University |
| issn | 2950-3299 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Oncology |
| spelling | doaj-art-4e8a6e6eb7294730a034e2eec3dacbfa2025-01-30T05:15:23ZengElsevierMolecular Therapy: Oncology2950-32992025-03-01331200932Attenuated titin protein expression is associated with advanced stages of ovarian cancerHarvey Sharma0Jaskaran Aujla1Asad Nawaz2Thabet Khasawneh3Ayesha Alvero4Robert T. Morris5Asma Basha6Laila Tutunji7Toshima Z. Parris8Khalil Helou9Ghassan M. Saed10Department 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 Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USADepartment of Gynecologic Oncology, Karmanos Cancer Institute, Detroit, MI 48201, USADepartment of Obstetrics and Gynecology, University of Jordan School of Medicine, 226 Queen Rania Al Abdullah Street, Amman 11942, JordanDepartment of Obstetrics and Gynecology, University of Jordan School of Medicine, 226 Queen Rania Al Abdullah Street, 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, 41685 Gothenburg, 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, 41685 Gothenburg, SwedenDepartment of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, MI 48201, USA; Department of Gynecologic Oncology, Karmanos Cancer Institute, Detroit, MI 48201, USA; Department of Obstetrics and Gynecology, University of Jordan School of Medicine, 226 Queen Rania Al Abdullah Street, Amman 11942, Jordan; Corresponding author: Dr. Ghassan M. Saed, Associate Professor of Gynecologic Oncology, Director of Ovarian Cancer Biology Research, Department of Obstetrics and Gynecology, Wayne State University School of Medicine, 275 East Hancock Street, Detroit, MI 48201, USA.This study explores the role of titin, a giant muscle protein, in the progression of epithelial ovarian cancer (EOC). We examined titin levels in tissues and sera from EOC patients across stages I–IV and in chemoresistant EOC cells. Tissue samples underwent immunohistochemistry, and serum titin levels were measured using ELISA. Quantitative real-time PCR analyzed titin mRNA in cell lines, including chemosensitive, chemoresistant, and normal ovarian cells. Notably, elevated titin levels were detected in 90.9% of stage I tissues compared to only 14.3% of stage III and IV tissues. Serum titin levels were consistently decreased across all stages relative to healthy controls, with a gradual decrease in expression from stages I to IV. Additionally, titin levels were significantly higher in normal ovarian epithelial cells compared to both chemosensitive and chemoresistant EOC cells, albeit significantly higher in chemosensitive than chemoresistant cells. These findings suggest the possible role of decreased titin levels as a marker for therapeutic intervention, particularly in advanced-stage and chemoresistant EOC. Further elucidation of the mechanisms underlying attenuated titin expression holds promise for advancing our understanding of ovarian cancer pathogenesis.http://www.sciencedirect.com/science/article/pii/S2950329925000013MT: Regular Issueattenuated titin expressionchemoresistanceovarian cancertherapeutic markertitin mutations |
| spellingShingle | Harvey Sharma Jaskaran Aujla Asad Nawaz Thabet Khasawneh Ayesha Alvero Robert T. Morris Asma Basha Laila Tutunji Toshima Z. Parris Khalil Helou Ghassan M. Saed Attenuated titin protein expression is associated with advanced stages of ovarian cancer Molecular Therapy: Oncology MT: Regular Issue attenuated titin expression chemoresistance ovarian cancer therapeutic marker titin mutations |
| title | Attenuated titin protein expression is associated with advanced stages of ovarian cancer |
| title_full | Attenuated titin protein expression is associated with advanced stages of ovarian cancer |
| title_fullStr | Attenuated titin protein expression is associated with advanced stages of ovarian cancer |
| title_full_unstemmed | Attenuated titin protein expression is associated with advanced stages of ovarian cancer |
| title_short | Attenuated titin protein expression is associated with advanced stages of ovarian cancer |
| title_sort | attenuated titin protein expression is associated with advanced stages of ovarian cancer |
| topic | MT: Regular Issue attenuated titin expression chemoresistance ovarian cancer therapeutic marker titin mutations |
| url | http://www.sciencedirect.com/science/article/pii/S2950329925000013 |
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