Validation of Novel Prognostic Biomarkers for Early-Stage Clear-Cell, Endometrioid and Mucinous Ovarian Carcinomas Using Immunohistochemistry

Abstract

Early-stage (I and II) ovarian carcinoma patients generally have good prognosis. Yet, some patients die earlier than expected. Thus, it is important to stratify early-stage patients into risk groups to identify those in need of more aggressive treatment regimens. The prognostic value of 29 histotype-specific biomarkers identified using RNA sequencing was evaluated for early-stage clear-cell (CCC), endometrioid (EC) and mucinous (MC) ovarian carcinomas (n = 112) using immunohistochemistry on tissue microarrays. Biomarkers with prognostic significance were further evaluated in an external ovarian carcinoma data set using the web-based Kaplan-Meier plotter tool. Here, we provide evidence of aberrant protein expression patterns and prognostic significance of 17 novel histotype-specific prognostic biomarkers [10 for CCC (ARPC2, CCT5, GNB1, KCTD10, NUP155, RPL13A, RPL37, SETD3, SMYD2, TRIO), three for EC (CECR1, KIF26B, PIK3CA), and four for MC (CHEK1, FOXM1, KIF23, PARPBP)], suggesting biological heterogeneity within the histotypes. Combined predictive models comprising the protein expression status of the validated CCC, EC and MC biomarkers together with established clinical markers (age, stage, CA125, ploidy) improved the predictive power in comparison with models containing established clinical markers alone, further strengthening the importance of the biomarkers in ovarian carcinoma. Further, even improved predictive powers were demonstrated when combining these models with our previously identified prognostic biomarkers PITHD1 (CCC) and GPR158 (MC). Moreover, the proteins demonstrated improved risk prediction of CCC-, EC-, and MC-associated ovarian carcinoma survival. The novel histotype-specific prognostic biomarkers may not only improve prognostication and patient stratification of early-stage ovarian carcinomas, but may also guide future clinical therapy decisions.

Identification of Differentially Expressed Genes Associated With Precocious Puberty by Suppression Subtractive Hybridization in Goat Pituitary Tissues

“…SLC25A5 (solute carrier family 25 member 5) facilitated the transport of molecules involved in the urea and citric acid cycles, oxidative phosphorylation, DNA maintenance and iron metabolism processes [32,33]. In the dysregulated expression of androgen metabolism genes and genetic analysis in hypospadias, the data provided direct evidence that SLC25A5 may contribute the genetic etiology of hypospadias [34]. In the bovine reproduction study, SLC25A5 gene were found high expressed in the SSH library of bovine blastocyst [35].…”

DEAD-Box Helicase 4 (Ddx4)+ Stem Cells Sustain Tumor Progression in Non-Serous Ovarian Cancers

“…In particular, upregulated DEGs included SIRT1 , which is involved in stemness [ 28 ] and chemoresistance [ 29 ], SNAIL2, which participates in EMT and collagen remodeling [ 30 , 31 ], and SIRT2 , CTGF , IL-11 and MMP13 , involved in cell migration, invasiveness as well as resistance to platinum and paclitaxel [ 32 , 33 , 34 , 35 , 36 ]. Other upregulated DEGs, such as MCM-6 , TGFB-1 , HMGA2 and FOXM1 , are involved in similar cancer-related processes [ 37 , 38 , 39 , 40 , 41 , 42 ], while downregulated DEGs, such as LOX and TIMP-1 (which are associated with poor cancer prognosis [ 43 , 44 , 45 ]), were observed in A2780 co-cultured with both A1 and A2 derived ML-Ddx4 + cells. Among these gene expression alterations, only ADGRL2 and PES1 upregulation were observed in A2780 cells conditioned with control ML-Ddx4 + cells, in a similar fashion to what emerged from the A1-related co-culture.…”

Identification of the Hub Genes Associated with the Prognosis of Ovarian Cancer Patients via Integrated Bioinformatics Analysis and Experimental Validation

“…In ovarian cancer studies, Engqvist et al indicated that KIF23 may serve as a novel prognostic biomarker for early-stage clear-cell, endometrioid and mucinous ovarian carcinomas using immunohistochemistry. 59 Mechanistic studies revealed that KIF23 that was targeted by miR-424/503 cluster promoted oncogenic performance of ovarian cancer cells in vitro. 60 Collectively, our results suggested that the oncogenic role of KIF23 in ovarian cancer and KIF23 may be a poor prognostic biomarker in ovarian cancer.…”