28511565 OR The role of membrane transporters in ovarian cancer chemoresistance and prognosis Dotaz Zobrazit nápovědu
INTRODUCTION: Ovarian cancer has the highest mortality rate of all cancers in women. There is currently no effective method for early diagnosis, limiting the precision of clinical expectations. Predictions of therapeutic efficacy are currently not available either. Specifically, the development of chemoresistance against conventional chemotherapy poses a fundamental complication. Some membrane transporters have been reported to influence chemoresistance, which is often associated with a poor prognosis. Areas covered: The aim of this article is to review the existing information about membrane transporters and their role in both ovarian cancer chemoresistance and its outcomes. We then highlight limitations of current methodologies and suggest alternatives providing avenues for future research. Expert opinion: Membrane transporters play an important role in development of chemoresistance and affect prognosis of ovarian cancer patients; however, due to variations in methodology and in patient populations, their specific roles have yet to be clarified. For further evaluation of the clinical utility of membrane transporters, it is essential to validate results and improve methods for marker assessment across laboratories. A promising area for future research is to identify the genetic variability in potential markers in peripheral blood. These markers would then stratify patients into defined groups for optimal intervention.
- MeSH
- antitumorózní látky farmakologie MeSH
- chemorezistence MeSH
- lidé MeSH
- membránové transportní proteiny metabolismus MeSH
- nádorové biomarkery genetika MeSH
- nádory vaječníků farmakoterapie genetika patologie MeSH
- prognóza MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Membrane transporters (such as ABCs, SLCs and ATPases) act in carcinogenesis and chemoresistance development, but their relevance for prognosis of epithelial ovarian cancer (EOC) remains poorly understood. We evaluated the gene expression profile of 39 ABC and 12 SLC transporters and three ATPases in EOC tissues and addressed their putative role in prognosis and clinical course of EOC patients. Relative gene expression in a set of primary EOC (n=57) and in control ovarian tissues (n=14) was estimated and compared with clinical data and survival of patients. Obtained data were validated in an independent set of patients (n=60). Six ABCs and SLC22A18 gene were significantly overexpressed in carcinomas when compared with controls, while expression of 12 ABCs, five SLCs, ATP7A and ATP11B was decreased. Expression of ABCA12, ABCC3, ABCC6, ABCD3, ABCG1 and SLC22A5 was higher in high grade serous carcinoma compared with other subtypes. ABCA2 gene expression significantly associated with EOC grade in both sets of patients. Notably, expression level of ABCA9, ABCA10, ABCC9 and SLC16A14 significantly associated with progression-free survival (PFS) of the disease in either pilot or validation sets. ABCG2 level associated with PFS in the pooled set of patients. In conclusion, ABCA2, ABCA9, ABCA10, ABCC9, ABCG2 and SLC16A14 present novel putative markers of EOC progression and together with the revealed relationship between ABCA12, ABCC3, ABCC6, ABCD3, ABCG1 and SLC22A5 expression, and high grade serous type of EOC should be further examined by larger follow-up study.
- MeSH
- exprese genu * MeSH
- lidé středního věku MeSH
- lidé MeSH
- membránové transportní proteiny genetika MeSH
- nádory vaječníků genetika patologie MeSH
- pilotní projekty MeSH
- přežití po terapii bez příznaků nemoci MeSH
- prognóza MeSH
- progrese nemoci MeSH
- regulace genové exprese u nádorů MeSH
- reprodukovatelnost výsledků MeSH
- senioři MeSH
- stanovení celkové genové exprese metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH