Gene expression of membrane transporters: Importance for prognosis and progression of ovarian carcinoma

Abstract

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.

Expression of oxysterol pathway genes in oestrogen‐positive breast carcinomas

“…In summary, the present study demonstrates that the downregulation of certain efflux pumps in the tumours of patients with high grade (ABCA9/10) or with poor DFS (ABCG2) has prognostic importance for ER+ breast carcinomas, similar to what was recently demonstrated in patients with ovarian carcinoma …”

“…It remains to be established whether this effect is connected with the transport of other substrates, different regulation mechanisms in ER+ breast tumours or with other regulatory aspects (eg. epigenetic events such as miRNA expression or protein stabilization).In summary, the present study demonstrates that the downregulation of certain efflux pumps in the tumours of patients with high grade (ABCA9/10) or with poor DFS (ABCG2) has prognostic importance for ER+ breast carcinomas, similar to what was recently demonstrated in patients with ovarian carcinoma 35. A positive correlation of ESR1 with age, in addition to the higher ESR1 expression in postmenopausal patients observed in this study both reflect the current view that the prognosis of the patients with ER+ breast cancer should be distinguished by the menopausal status 36.…”

Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy

“…Strikingly, the gene expression of MCT12 is most frequently downregulated in tumors compared with non‐neoplastic tissues in the examined cancer entities. Only few genomewide gene expression profiling studies are available, indicating altered expression of MCT isoforms e.g., in hepatocellular carcinoma,38 thyroid cancer,39 adrenocortical cancer,40 or ovarian cancer41 but the precise molecular mechanisms behind altered MCT expression are not revealed. Given that tumor growth is a highly energy consuming process and tumors demonstrate metabolic reprogramming and considerable metabolic plasticity, other MCT isoforms presumably play an important role in cancer development and progression as suppliers of nutrients or exporters of metabolic end products.…”

The Importance of Steroid Uptake and Intracrine Action in Endometrial and Ovarian Cancers

“…Some of these ABC proteins are associated with drug resistance in ovarian and endometrial cancers. For example, overexpression of ABCC1 and ABCG2 in serous ovarian cancer reduces the cellular accumulation of anticancer drugs, and this leads to the development of MDR and poor prognosis (Kunicka and Soucek, 2014; Elsnerova et al, 2016). Furthermore, ABCC1 is associated with higher tumor grade, and ABCC4 with reduced progression-free survival of patients with ovarian cancer (Ween et al, 2015).…”