Transcriptomic Characterization of Endometrioid, Clear Cell, and High-Grade Serous Epithelial Ovarian Carcinoma

Abstract

Endometrioid carcinoma (EC) and clear cell carcinoma (CC) histotypes of epithelial ovarian cancer are understudied compared with the more common high-grade serous carcinomas (HGSC). We therefore sought to characterize EC and CC transcriptomes in relation to HGSC. Following bioinformatics processing and gene abundance normalization, differential expression analysis of RNA sequence data collected on fresh-frozen tumors was completed with nonparametric statistical analysis methods (55 ECs, 19 CCs, 112 HGSCs). Association of gene expression with progression-free survival (PFS) was completed with Cox proportional hazards models. Eight additional multi-histotype expression array datasets ( = 852 patients) were used for replication. In the discovery set, tumors generally clustered together by histotype. Thirty-two protein-coding genes were differentially expressed across histotype ( < 1 × 10) and showed similar associations in replication datasets, including , and Nine genes associated with PFS ( < 0.0001) showed similar associations in replication datasets. In particular, we observed shorter PFS time for CC and EC patients with high gene expression for , and, whereas, the converse was observed for HGSC patients. The results suggest important histotype differences that may aid in the development of treatment options, particularly those for patients with EC or CC. We present replicated findings on transcriptomic differences and how they relate to clinical outcome for two of the rarer ovarian cancer histotypes of EC and CC, along with comparison with the common histotype of HGSC. .

Systematic Identification of Characteristic Genes of Ovarian Clear Cell Carcinoma Compared with High-Grade Serous Carcinoma Based on RNA-Sequencing

“…Similar to our study, transcriptomic analysis revealed the expression profiles of ovarian cancer subtypes. Fridley et al performed RNA-seq to identify differentially expressed genes in HGSC, CCC, and endometrioid carcinoma (EC) [23]. In this report, increased expression levels of FBXO8 , RAPH1 , CEP44 , KIAA0513 , FAM155A , and RXFP1 were found in CCC compared to HGSC, similar to our study.…”

Designer Self‐Assembling Peptide Hydrogels to Engineer 3D Cell Microenvironments for Cell Constructs Formation and Precise Oncology Remodeling in Ovarian Cancer

“…[ 212 ] The comparative molecular studies that fail to recognize the histopathological origins are no longer effective. [ 150,213 ] Novel ovarian cancer cell models are ongoing need to reflect the main scientific aspects for precise oncology remodeling in vitro, such as cancer cell behaviors, exosomes, and acquired chemoresistance, cell–cell coculture and cell–ECM interactions, and tumor spheroids formation, which elaborately recapitulate cell–cell and cell–ECM interactions in ovarian cancer development, progression, metastasis, dissemination or therapeutic recurrence and relapse. To capture the oncogenic drivers and tumor biology of HGSOC, fallopian tube‐based model systems may define the physiology and susceptibility of this epithelium to tumorous transformation.…”

Identification of Core Genes Involved in the Metastasis of Clear Cell Renal Cell Carcinoma

“…18 Accumulating evidence proved that CCNB2 was overexpressed in various human cancers, such as lung cancer, colorectal adenocarcinoma, and ovarian carcinoma. [19][20][21] Moreover, it has been found that advanced clinical stage and worse metastasis status were associated with the elevated expression of circulating CCNB2. 22 As a biomarker, it has been reported that overexpression of CCNB2 could act as an independent predictor of poor prognosis in patients with lung adenocarcinoma and breast cancer.…”