Harkema, T.P.G. (Thialda) (2017) MALDI-FTICR profiling among BRCA 1/2 mutation carriers with and without ovarian cancer : a case control study. thesis, Medicine.
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Abstract
Background: Ovarian cancer is the most lethal gynaecological malignancy and has an elevated risk on development among BRCA1/2 mutation carriers. Since there is currently no sufficient screening or non-invasive risk reducing approach to ovarian cancer, there is obvious need for the development of a new screening tool. We evaluated whether proteomics can provide an alternative or add-on for ovarian cancer screening in the high risk population of BRCA1/2 mutation carriers. Methods: We analysed 117 serum samples of 40 women with advanced stage ovarian cancer and 77 healthy controls by means of MALDI-FTICR mass spectrometry. All patients and controls were BRCA1/2 mutation carriers. To evaluate the diagnostic properties of MALDIFTICR mass spectrometry, logistic ridge regression was applied, and sensitivity, specificity and Area Under the Curve (AUC) were estimated. Validation was performed by bootstrapping. To evaluate whether MALDI/FTICR has additional value to CA125, we calculated sensitivity and specificity of MALDI-FTICR combined with CA125 considering two definitions for a positive test outcome: both a positive MALDI-FTICR MS and a positive serum CA125 outcome, or either a positive MALDI-FTICR MS or a positive serum CA125 outcome. Results: MALDI-FTICR MS was able to distinguish BRCA1/2 associated advanced stage ovarian cancer cases from healthy BRCA1/2 mutation carriers with a sensitivity of 91%, a specificity of 42.5% and a AUC of 0.727. In comparison to serum CA125 alone, the addition of MALDI-FTICR to CA125 measurements was able to improve sensitivity from 62.9% to 78.8% with a specificity of 87.2%, in case of either a positive MALDI-FTICR or positive CA125 outcome as defined positive outcome. When stated a positive outcome when both MALDI-FTICR and CA125 outcome were positive, sensitivity and specificity were 24,2% and 97,4% respectively. Discussion: MALDI-FTICR is able to distinguish highly selected patients with advanced ovarian cancer from healthy controls among BRCA1/2 mutation carriers and to improve the sensitivity of CA125 alone when added to the CA125 measurements. However, these findings require further evaluation on identifying asymptomatic women with a low grade tumour. The ultimate goal is to discover a protein profile that can distinguish women with a small tumour volume in a healthy population, with a high positive- and negative predictive value.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Supervisors UMCG: and Bock, Prof. Dr. G.H. de and Mourits, Prof. M.J.E. |
| Supervisor name: | Supervisor LUMC: and Mesker, Dr. W.E. |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 10:59 |
| Last Modified: | 25 Jun 2020 10:59 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/1951 |
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