In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 75, No. 15_Supplement ( 2015-08-01), p. 4631-4631
Kurzfassung:
Objective: Although most ovarian cancer patients respond initially to the standard of care involving carboplatinum/paclitaxel-based chemotherapy, the majority will recur with chemotherapeutically resistant disease. Unfortunately, no clinical biomarker(s) for predicting or monitoring chemotherapeutic resistance are available. We sought to identify shed and/or secreted proteins from paclitaxel-resistant human ovarian cancer cells and identify whether any of these correlate with ovarian cancer patient outcome. Methods: A proteomic analysis of secretomes from high grade serous ovarian cancer (HGSOC) cells (OV90) was compared to that from a syngeneic paclitaxel-resistant variant (OV90-TR) and a cancer cell line developed from a chemorefractory HGSOC patient. Associations between the identified candidates and patient outcome were assessed from publicly available transcript expression data (n = 545 ovarian cancer patients) and validated independently (n = 795 ovarian cancer patients). Results: Among the 81 differentially abundant proteins identified (q & lt;0.05) from paclitaxel-sensitive vs -resistant HGSOC cell secretomes, AKAP12 was verified to be elevated at the protein and transcript level in all models of paclitaxel-resistant HGSOC. Further, elevated AKAP12 transcript expression was found to significantly correlate with poor progression-free (Hazard Ratio = 1.487 (± 0.148), p = 0.0085 (± 0.002) and overall (Hazard Ratio = 1.22 (± 0.08), p = 0.009 (± 0.013) survival. Conclusions: These findings suggest that elevation and efflux of AKAP12 is characteristic of paclitaxel-resistant HGSOC cells and that elevated AKAP12 expression correlates with poor ovarian cancer patient survival. Citation Format: Nicholas Bateman, Elizabeth Jaworski, Guisong Wang, Elizabeth Dubil, Charlotte Marcus, Kelly Conrads, Pang-ning Teng, Brian Hood, Chad Hamilton, Larry Maxwell, Kathleen Darcy, Thomas Conrads. AKAP12 is elevated in paclitaxel-resistant ovarian cancer cells and correlates with poor ovarian cancer patient survival. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4631. doi:10.1158/1538-7445.AM2015-4631
Materialart:
Online-Ressource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2015-4631
Sprache:
Englisch
Verlag:
American Association for Cancer Research (AACR)
Publikationsdatum:
2015
ZDB Id:
2036785-5
ZDB Id:
1432-1
ZDB Id:
410466-3
