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Proteomics-Derived Biomarker Panel Improves Diagnostic Precision to Classify Endometrioid and High-grade Serous Ovarian Carcinoma
- Source :
- Clinical Cancer Research. 25:4309-4319
- Publication Year :
- 2019
- Publisher :
- American Association for Cancer Research (AACR), 2019.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Cancer Research
Proteome
endocrine system diseases
Quantitative proteomics
Proteomics
03 medical and health sciences
0302 clinical medicine
Ovarian carcinoma
Biomarkers, Tumor
Carcinoma
medicine
Humans
Ovarian Neoplasms
Tissue microarray
business.industry
Prognosis
medicine.disease
female genital diseases and pregnancy complications
Cystadenocarcinoma, Serous
Serous fluid
030104 developmental biology
ROC Curve
Oncology
030220 oncology & carcinogenesis
Cancer research
Immunohistochemistry
Female
Differential diagnosis
business
Carcinoma, Endometrioid
Subjects
Details
- ISSN :
- 15573265 and 10780432
- Volume :
- 25
- Database :
- OpenAIRE
- Journal :
- Clinical Cancer Research
- Accession number :
- edsair.doi.dedup.....5d163facfc4475d9bf050fff52214a6b