Gene Expression Profiling Reveals Novel Candidate Markers of Ovarian Carcinoma Intraperitoneal Metastasis

Abstract

Epithelial ovarian cancer (EOC) has the highest mortality among gynecological carcinomas. The lack of specific markers for prognostic determination of EOC progression hinders the search for novel effective therapies.The aim of the present study was (i) to explore differences in expressions of ATP-binding cassette (ABC) and solute carrier (SLC) transporter genes, genes associated with drug metabolism and cell cycle regulation between control ovarian tissues (n = 14), primary EOCs (n = 44) and intraperitoneal metastases (n = 29); (ii) to investigate associations of gene expression levels with prognosis of patients with intraperitoneal metastases.In all tissue samples, transcript levels of the above target genes were assessed using quantitative real-time PCR. Gene expression levels were compared between particular tissue types and evaluated with regard to progression-free survival (PFS) and drug-resistance status of patients with metastases.Gene expression of ABCA7 significantly increased and that of ESR2 decreased in the order control ovarian tissues - primary EOCs - metastases. High expressions of ABCA2/8/9/10, ABCB1, ABCC9, ABCG2, ATP7A, SLC16A14, and SOD3 genes were significantly associated with longer progression-free survival of patients. In intraperitoneal metastases, expression of all of these genes highly correlated and indicated prognostic profile. Transporters from the ABCA family, ABCG2, and ESR2 are involved mainly in lipid metabolism, membrane transport, and cell proliferation. These processes are thus probably the most important for EOC progression.Based on these results, we have proposed novel markers of ovarian carcinoma progression and metastatic spread which might be potentially useful as therapeutic targets. Their significance should be further explored on a larger independent set of patients.

Association of ABC gene profiles with time to progression and resistance in ovarian cancer revealed by bioinformatics analyses

“…This could be attributed to the nondirect relationships between these genes and features tested as well as the clinical differences between the two patient sets. Notably, these results support the conclusion of our previous studies, where especially the role of ABCA9, ABCA10, and ABCC9 transporters in OC progression and metastatic spread was stressed. Connection between high expression of ABC transporters from the subfamily A and poor outcome in serous OC was recently discussed in the study conducted by Hedditch et al Furthermore, the relatively small number of patients and the differences between clinical characteristics of both OC patient cohorts may be seen as limitations of the current study.…”

“…Verification of cDNA quality was performed by PCR amplification of ubiquitin C fragment. Before quantitative real‐time PCR, cDNA was preamplified; this step was described in detail in our previous works . qRT‐PCR was performed on Viia7 RT‐PCR System (Life Technologies, Carlsbad, CA, USA), with the use of TaqMan Gene Expression Assay (Life technologies) specific for each gene.…”

Overexpression of kinesin family member 20A is associated with unfavorable clinical outcome and tumor progression in epithelial ovarian cancer

“… 24 However, to date, there is lack of sensitive molecular bio-markers for detecting early intraperitoneal metastasis. 28 Our findings show that KIF20A expression correlates strongly with intraperitoneal metastasis in EOC. Additionally, Cox regression analyses showed that intraperitoneal metastasis is an important factor that shortens the OS of EOC.…”

“…Therefore, KIF20A can been seen as a biomarker for detecting intraperitoneal metastasis at the early stages of EOC and may contribute to improving survival of EOC patients. 24 , 28 …”

ATP‑binding cassette transporter A7 accelerates epithelial‑to‑mesenchymal transition in ovarian cancer cells by upregulating the transforming growth factor‑β signaling pathway

“…ABC transporters undertake the transport of various inflammatory mediators and lipids directly relevant to tumor progression in OC ( 4 ). Elsnerova et al ( 5 ) reported that the expression of ABCA7 was significantly higher in OC than in control ovarian tissue, and ABCA7 was upregulated in metastatic tumor tissue compared with primary OC. Additionally, increased expression of ABCA7 was significantly associated with poor outcomes in patients with OC ( 5 , 6 ).…”