KI67 and DLX2 predict increased risk of metastasis formation in prostate cancer: a targeted molecular approach
Background:There remains a need to identify and validate biomarkers for predicting prostate cancer (CaP) outcomes using robust and routinely available pathology techniques to identify men at most risk of premature death due to prostate cancer. Previous immunohistochemical studies suggest the prolife...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
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Cancer Research UK
2016
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| Online Access: | https://eprints.nottingham.ac.uk/34569/ |
| _version_ | 1848794884453957632 |
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| author | Green, William J.F. Ball, Graham Hulman, Geoffrey Johnson, Catherine Van Schalwyk, Gerry Ratan, Hari L. Soria, Daniel Garibaldi, Jonathan M. Parkinson, Richard Hulman, Joshua Rees, Robert Powe, Desmond G. |
| author_facet | Green, William J.F. Ball, Graham Hulman, Geoffrey Johnson, Catherine Van Schalwyk, Gerry Ratan, Hari L. Soria, Daniel Garibaldi, Jonathan M. Parkinson, Richard Hulman, Joshua Rees, Robert Powe, Desmond G. |
| author_sort | Green, William J.F. |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Background:There remains a need to identify and validate biomarkers for predicting prostate cancer (CaP) outcomes using robust and routinely available pathology techniques to identify men at most risk of premature death due to prostate cancer. Previous immunohistochemical studies suggest the proliferation marker Ki67 might be a predictor of survival, independently of PSA and Gleason score. We performed a validation study of Ki67 as a marker of survival and disease progression and compared its performance against another candidate biomarker, DLX2, selected using artificial neural network analysis.
Methods: A tissue microarray (TMA) was constructed from transurethral resected prostatectomy histology samples (n=192). Artificial neural network analysis was used to identify candidate markers conferring increased risk of death and metastasis in a public cDNA array. Immunohistochemical analysis of the TMA was carried out and univariate and multivariate tests performed to explore the association of tumour protein levels of Ki67 and DLX2 with time to death and metastasis.
Results: Univariate analysis demonstrated Ki67 as predictive of CaP-specific survival (DSS; P=0.022), and both Ki67 (P=0.025) and DLX2 (P=0.001) as predictive of future metastases. Multivariate analysis demonstrated Ki67 as independent of PSA, Gleason score and D’Amico risk category for DSS (HR=2.436,P=0.029) and both Ki67 (HR=3.296,P=0.023) and DLX2 (HR=3.051,P=0.003) as independent for future metastases.
Conclusions: High Ki67 expression is only present in 6.8% of CaP patients and is predictive of reduced survival and increased risk of metastasis, independent of PSA, Gleason score and D’Amico risk category. DLX2 is a novel marker of increased metastasis risk found in 73% patients and 8.2% showed co-expression with a high Ki67 score. Two cancer cell proliferation markers, Ki67 and DLX2, may be able to inform clinical decision-making when identifying patients for active surveillance. |
| first_indexed | 2025-11-14T19:23:17Z |
| format | Article |
| id | nottingham-34569 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:23:17Z |
| publishDate | 2016 |
| publisher | Cancer Research UK |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-345692020-05-04T17:55:26Z https://eprints.nottingham.ac.uk/34569/ KI67 and DLX2 predict increased risk of metastasis formation in prostate cancer: a targeted molecular approach Green, William J.F. Ball, Graham Hulman, Geoffrey Johnson, Catherine Van Schalwyk, Gerry Ratan, Hari L. Soria, Daniel Garibaldi, Jonathan M. Parkinson, Richard Hulman, Joshua Rees, Robert Powe, Desmond G. Background:There remains a need to identify and validate biomarkers for predicting prostate cancer (CaP) outcomes using robust and routinely available pathology techniques to identify men at most risk of premature death due to prostate cancer. Previous immunohistochemical studies suggest the proliferation marker Ki67 might be a predictor of survival, independently of PSA and Gleason score. We performed a validation study of Ki67 as a marker of survival and disease progression and compared its performance against another candidate biomarker, DLX2, selected using artificial neural network analysis. Methods: A tissue microarray (TMA) was constructed from transurethral resected prostatectomy histology samples (n=192). Artificial neural network analysis was used to identify candidate markers conferring increased risk of death and metastasis in a public cDNA array. Immunohistochemical analysis of the TMA was carried out and univariate and multivariate tests performed to explore the association of tumour protein levels of Ki67 and DLX2 with time to death and metastasis. Results: Univariate analysis demonstrated Ki67 as predictive of CaP-specific survival (DSS; P=0.022), and both Ki67 (P=0.025) and DLX2 (P=0.001) as predictive of future metastases. Multivariate analysis demonstrated Ki67 as independent of PSA, Gleason score and D’Amico risk category for DSS (HR=2.436,P=0.029) and both Ki67 (HR=3.296,P=0.023) and DLX2 (HR=3.051,P=0.003) as independent for future metastases. Conclusions: High Ki67 expression is only present in 6.8% of CaP patients and is predictive of reduced survival and increased risk of metastasis, independent of PSA, Gleason score and D’Amico risk category. DLX2 is a novel marker of increased metastasis risk found in 73% patients and 8.2% showed co-expression with a high Ki67 score. Two cancer cell proliferation markers, Ki67 and DLX2, may be able to inform clinical decision-making when identifying patients for active surveillance. Cancer Research UK 2016-06-23 Article PeerReviewed Green, William J.F., Ball, Graham, Hulman, Geoffrey, Johnson, Catherine, Van Schalwyk, Gerry, Ratan, Hari L., Soria, Daniel, Garibaldi, Jonathan M., Parkinson, Richard, Hulman, Joshua, Rees, Robert and Powe, Desmond G. (2016) KI67 and DLX2 predict increased risk of metastasis formation in prostate cancer: a targeted molecular approach. British Journal of Cancer . ISSN 0007-0920 http://www.nature.com/bjc/journal/vaop/ncurrent/pdf/bjc2016169a.pdf doi:10.1038/bjc.2016.169 doi:10.1038/bjc.2016.169 |
| spellingShingle | Green, William J.F. Ball, Graham Hulman, Geoffrey Johnson, Catherine Van Schalwyk, Gerry Ratan, Hari L. Soria, Daniel Garibaldi, Jonathan M. Parkinson, Richard Hulman, Joshua Rees, Robert Powe, Desmond G. KI67 and DLX2 predict increased risk of metastasis formation in prostate cancer: a targeted molecular approach |
| title | KI67 and DLX2 predict increased risk of metastasis formation in prostate cancer: a targeted molecular approach |
| title_full | KI67 and DLX2 predict increased risk of metastasis formation in prostate cancer: a targeted molecular approach |
| title_fullStr | KI67 and DLX2 predict increased risk of metastasis formation in prostate cancer: a targeted molecular approach |
| title_full_unstemmed | KI67 and DLX2 predict increased risk of metastasis formation in prostate cancer: a targeted molecular approach |
| title_short | KI67 and DLX2 predict increased risk of metastasis formation in prostate cancer: a targeted molecular approach |
| title_sort | ki67 and dlx2 predict increased risk of metastasis formation in prostate cancer: a targeted molecular approach |
| url | https://eprints.nottingham.ac.uk/34569/ https://eprints.nottingham.ac.uk/34569/ https://eprints.nottingham.ac.uk/34569/ |