FXYD5 (Dysadherin) upregulation predicts shorter survival and reveals platinum resistance in high-grade serous ovarian cancer patients

Abstract

BACKGROUND: High-grade serous ovarian carcinoma (HGSOC) is generally associated with a very dismal prognosis. Nevertheless, patients with similar clinicopathological characteristics can have markedly different clinical outcomes. Our aim was the identification of novel molecular determinants influencing survival. METHODS: Gene expression profiles of extreme HGSOC survivors (training set) were obtained by microarray. Differentially expressed genes (DEGs) and enriched signalling pathways were determined. A prognostic signature was generated and validated on curatedOvarianData database through a meta-analysis approach. The best prognostic biomarker from the signature was confirmed by RT-qPCR and by immunohistochemistry on an independent validation set. Cox regression model was chosen for survival analysis. RESULTS: Eighty DEGs and the extracellular matrix-receptor (ECM-receptor) interaction pathway were associated to extreme survival. A 10-gene prognostic signature able to correctly classify patients with 98% of accuracy was identified. By an 'in-silico' metaanalysis, overexpression of FXYD domain-containing ion transport regulator 5 (FXYD5), also known as dysadherin, was confirmed in HGSOC short-term survivors compared to long-term ones. Its prognostic and predictive power was then successfully validated, both at mRNA and protein level, first on training than on validation sample set. CONCLUSION: We demonstrated the possible involvement of FXYD5 and ECM-receptor interaction signal pathway in HCSOC survival and prognosis.

Integrated Analysis of Prognostic and Immune Associated Integrin Family in Ovarian Cancer

“…Here, we analyzed two distinct GEO datasets which compared the metastasis ovarian cancer to primary ovarian cancer. In the GSE131978 (Tassi et al, 2019 ) dataset, a group of primary OC samples were compared to a group of omental metastasis OC samples. The result showed ITGA3/7 and ITGB4 were significantly higher expressed in metastasis OC samples, ITGAV and ITGB1 were significantly higher expressed in primary OC samples ( Figure 4A ).…”

“…GEO is a public functional genomic data repository contains numerous array and sequence-based study data. After searching the GEO database associated with ovarian cancer, GSE26712 (Bonome et al, 2008 ) was selected to validate GEPIA tumor/normal comparison results; GSE30587 (Brodsky et al, 2014 ) and GSE131978 GPL96 (Tassi et al, 2019 ) were selected to analyze the association of integrin members with ovarian cancer metastasis; GSE30161 (Ferriss et al, 2012 ), GSE51373 (Koti et al, 2013 ) and GSE131978 GPL570 (Tassi et al, 2019 ) were selected to analyze the association of integrin members with ovarian cancer chemoresistance. The data of selected GEO datasets were downloaded and reanalyzed with Graphpad Prism 8.0.1.…”

Integrated Transcriptomic Analysis Reveals the Molecular Mechanism of Meningiomas by Weighted Gene Coexpression Network Analysis

“…Moreover, ID3 was reported to act as a biomarker promoting the stemness of intrahepatic cholangiocarcinoma by promoting the transcriptional activity of β-catenin [37]. Furthermore, high-grade serous ovarian carcinoma patients with higher expression of FXYD5 owned a shorter survival time than patients with lower expression of FXYD5, and FXYD5 played a critical role in survival and prognosis of HCSOC [38]. Similarly, biological experiments in vitro and in vivo showed that FXYD5 promoted the metastasis of ovarian cancer cells via TGF-β/SMAD signaling pathways [39].…”

Transcriptome-based Stemness Indices Analysis Reveals Platinum-based Chemotheraputic Response Indicators in Advanced-stage Serous Ovarian Cancer

“…A p value < 0.05 was considered representing statistical signi cance. In addition, GSE131978 [40] and GSE51373 [10] datasets were selected to validate whether the key genes were associated with platinum sensitivity in advanced-stage SOC patients. In the study, 7 platinum-based chemotherapyresistant SOC samples of stage III-IV and 4 platinum-based chemotherapy-sensitive samples selected from GSE131978 (platform GPL570) were used in the analysis.…”