000			03040nam a22003377a 4500
003			OSt
005			20240305193717.0
008			221011b |||||||| |||| 00| 0 eng d
022			_a Online ISSN 1557-3265
022			_aPrint ISSN 1078-0432
028			_b Phone: +255 28 298 3384
028			_b Fax: +255 28 298 3386
028			_bEmail: vc@bugando.ac.tz
028			_b Website: www.bugando.ac.tz
040			_cDLC
041			_aEnglish
100			_aDylan Z Dieters-Castator _944669
245			_aProteomics-Derived Biomarker Panel Improves Diagnostic Precision to Classify Endometrioid and High-grade Serous Ovarian Carcinoma
260			_aMwanza, Tanzania: _bAmerican Association for Cancer Research & _b Catholic University of Health and Allied Sciences [CUHAS – Bugando] _c2019/7/15
300			_aPages 4309-4319
490			_v Clinical Cancer Research Volume 25 Issue 14
520			_aAbstract Purpose: Ovarian carcinomas are a group of distinct diseases classified by histotypes. As histotype-specific treatment evolves, accurate classification will become critical for optimal precision medicine approaches. Experimental Design: To uncover differences between the two most common histotypes, high-grade serous (HGSC) and endometrioid carcinoma, we performed label-free quantitative proteomics on freshly frozen tumor tissues (HGSC, n = 10; endometrioid carcinoma, n = 10). Eight candidate protein biomarkers specific to endometrioid carcinoma were validated by IHC using tissue microarrays representing 361 cases of either endometrioid carcinoma or HGSC. Results: More than 500 proteins were differentially expressed (P < 0.05) between endometrioid carcinoma and HGSC tumor proteomes. A ranked set of 106 proteins was sufficient to correctly discriminate 90% of samples. IHC validated KIAA1324 as the most discriminatory novel biomarker for endometrioid carcinoma. An 8-marker panel was found to exhibit superior performance for discriminating endometrioid carcinoma from HGSC compared with the current standard of WT1 plus TP53 alone, improving the classification rate for HGSC from 90.7% to 99.2%. Endometrioid carcinoma–specific diagnostic markers such as PLCB1, KIAA1324, and SCGB2A1 were also significantly associated with favorable prognosis within endometrioid carcinoma suggesting biological heterogeneity within this histotype. Pathway analysis of proteomic data revealed differences between endometrioid carcinoma and HGSC pertaining to estrogen and interferon signalling. Conclusions: In summary, these findings support the use of multi-marker panels for the differential diagnosis of difficult cases resembling endometrioid carcinoma and HGSC.
700			_a Peter F Rambau _922887
700			_aLinda E Kelemen _944488
700			_aGabrielle M Siegers _944670
700			_aGilles A Lajoie _944671
700			_aLynne-Marie Postovit _944672
700			_aMartin Köbel _944499
856			_y https://doi.org/10.1158/1078-0432.CCR-18-3818
942			_2ddc _cVM
999			_c19149 _d19149