Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy
Background: Developing therapies for cancer cachexia has not been successful to date, in part due to the challenges of achieving robust quantitative measures as a readout of patient treatment. Hence, identifying biomarkers to assess the outcomes of treatments for cancer cachexia is of great interest...
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| Format: | Article |
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MDPI AG
2022-11-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/22/5533 |
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| author | Zhipeng Cao Ingrid J. Burvenich Kening Zhao Clare Senko Jason Glab Renee Fogliaro Zhanqi Liu Irvin Jose Hamsa Puthalakath Nick J. Hoogenraad Laura D. Osellame Andrew M. Scott |
| author_facet | Zhipeng Cao Ingrid J. Burvenich Kening Zhao Clare Senko Jason Glab Renee Fogliaro Zhanqi Liu Irvin Jose Hamsa Puthalakath Nick J. Hoogenraad Laura D. Osellame Andrew M. Scott |
| author_sort | Zhipeng Cao |
| collection | DOAJ |
| description | Background: Developing therapies for cancer cachexia has not been successful to date, in part due to the challenges of achieving robust quantitative measures as a readout of patient treatment. Hence, identifying biomarkers to assess the outcomes of treatments for cancer cachexia is of great interest and important for accelerating future clinical trials. Methods: We established a novel xenograft model for cancer cachexia with a cachectic human PC3* cell line, which was responsive to anti-Fn14 mAb treatment. Using RNA-seq and secretomic analysis, genes differentially expressed in cachectic and non-cachectic tumors were identified and validated by digital droplet PCR (ddPCR). Correlation analysis was performed to investigate their impact on survival in cancer patients. Results: A total of 46 genes were highly expressed in cachectic PC3* tumors, which were downregulated by anti-Fn14 mAb treatment. High expression of the top 10 candidates was correlated with low survival and high cachexia risk in different cancer types. Elevated levels of LCN2 were observed in serum samples from cachectic patients compared with non-cachectic cancer patients. Conclusion: The top 10 candidates identified in this study are candidates as potential biomarkers for cancer cachexia. The diagnostic value of LCN2 in detecting cancer cachexia is confirmed in patient samples. |
| first_indexed | 2024-03-09T18:26:10Z |
| format | Article |
| id | doaj.art-2fd640a0d7d04510b8fc849a8913b9c0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T18:26:10Z |
| publishDate | 2022-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-2fd640a0d7d04510b8fc849a8913b9c02023-11-24T07:52:41ZengMDPI AGCancers2072-66942022-11-011422553310.3390/cancers14225533Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 TherapyZhipeng Cao0Ingrid J. Burvenich1Kening Zhao2Clare Senko3Jason Glab4Renee Fogliaro5Zhanqi Liu6Irvin Jose7Hamsa Puthalakath8Nick J. Hoogenraad9Laura D. Osellame10Andrew M. Scott11Department of Biochemistry and Genetics, La Trobe University, Melbourne, VIC 3086, AustraliaTumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, School of Cancer Medicine, La Trobe University, Melbourne, VIC 3084, AustraliaDepartment of Biochemistry and Genetics, La Trobe University, Melbourne, VIC 3086, AustraliaTumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, School of Cancer Medicine, La Trobe University, Melbourne, VIC 3084, AustraliaDepartment of Biochemistry and Genetics, La Trobe University, Melbourne, VIC 3086, AustraliaDepartment of Molecular Imaging and Therapy, Austin Health, Heidelberg, VIC 3084, AustraliaTumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, School of Cancer Medicine, La Trobe University, Melbourne, VIC 3084, AustraliaDepartment of Biochemistry and Genetics, La Trobe University, Melbourne, VIC 3086, AustraliaDepartment of Biochemistry and Genetics, La Trobe University, Melbourne, VIC 3086, AustraliaDepartment of Biochemistry and Genetics, La Trobe University, Melbourne, VIC 3086, AustraliaDepartment of Biochemistry and Genetics, La Trobe University, Melbourne, VIC 3086, AustraliaTumour Targeting Laboratory, Olivia Newton-John Cancer Research Institute, School of Cancer Medicine, La Trobe University, Melbourne, VIC 3084, AustraliaBackground: Developing therapies for cancer cachexia has not been successful to date, in part due to the challenges of achieving robust quantitative measures as a readout of patient treatment. Hence, identifying biomarkers to assess the outcomes of treatments for cancer cachexia is of great interest and important for accelerating future clinical trials. Methods: We established a novel xenograft model for cancer cachexia with a cachectic human PC3* cell line, which was responsive to anti-Fn14 mAb treatment. Using RNA-seq and secretomic analysis, genes differentially expressed in cachectic and non-cachectic tumors were identified and validated by digital droplet PCR (ddPCR). Correlation analysis was performed to investigate their impact on survival in cancer patients. Results: A total of 46 genes were highly expressed in cachectic PC3* tumors, which were downregulated by anti-Fn14 mAb treatment. High expression of the top 10 candidates was correlated with low survival and high cachexia risk in different cancer types. Elevated levels of LCN2 were observed in serum samples from cachectic patients compared with non-cachectic cancer patients. Conclusion: The top 10 candidates identified in this study are candidates as potential biomarkers for cancer cachexia. The diagnostic value of LCN2 in detecting cancer cachexia is confirmed in patient samples.https://www.mdpi.com/2072-6694/14/22/5533cancer cachexiabiomarkerRNA-seqLCN2 |
| spellingShingle | Zhipeng Cao Ingrid J. Burvenich Kening Zhao Clare Senko Jason Glab Renee Fogliaro Zhanqi Liu Irvin Jose Hamsa Puthalakath Nick J. Hoogenraad Laura D. Osellame Andrew M. Scott Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy Cancers cancer cachexia biomarker RNA-seq LCN2 |
| title | Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy |
| title_full | Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy |
| title_fullStr | Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy |
| title_full_unstemmed | Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy |
| title_short | Identification of Potential Biomarkers for Cancer Cachexia and Anti-Fn14 Therapy |
| title_sort | identification of potential biomarkers for cancer cachexia and anti fn14 therapy |
| topic | cancer cachexia biomarker RNA-seq LCN2 |
| url | https://www.mdpi.com/2072-6694/14/22/5533 |
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