The association between the expression of solute carrier transporters and the prognosis of pancreatic cancer

Autoři	MOHELNIKOVA-DUCHONOVA Beatrice BRYNYCHOVA Veronika HLAVAC Viktor KOCIK Matej OLIVERIUS Martin HLAVSA Jan HONSOVA Eva MAZANEC Jan KALA Zdeněk MELICHAR Bohuslav SOUCEK Pavel
Rok publikování	2013
Druh	Článek v odborném periodiku
Časopis / Zdroj	CANCER CHEMOTHERAPY AND PHARMACOLOGY
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
Doi	http://dx.doi.org/10.1007/s00280-013-2246-2
Obor	Onkologie a hematologie
Klíčová slova	Pancreatic cancer; SLC transporters; Gene expression; Survival; KRAS
Popis	The aim of this study was to investigate the prognostic significance of fourteen anticancer drug-relevant solute carrier transporters (SLCs) in pancreatic cancer in the context of clinical-pathological characteristics and the KRAS mutation status of tumors. Tumors and non-neoplastic pancreatic tissues were obtained from 32 histologically verified patients with pancreatic ductal adenocarcinoma. The transcript profile of SLCs was assessed using quantitative real-time PCR. KRAS mutations in exon 2 were assessed by high-resolution melting analysis and confirmed by sequencing. SLC22A3 and SLC22A18 were upregulated and SLC22A1, SLC22A2, SLC22A11, SLC28A1, SLC28A3 and SLC29A1 were downregulated when compared with non-neoplastic pancreatic tissues. Moreover, significantly lower levels of SLC22A1, SLC22A11 and SLC29A1 were found in tumors with angioinvasion. There was also a significantly higher transcript level of SLC28A1 in tumors with regional lymph nodes affected by metastasis. The study found that a high expression of SLC28A1 was significantly associated with poor overall survival in unselected patients. In contrast, a high expression of SLC22A3 or SLC29A3 was significantly associated with longer overall survival in patients treated with nucleoside analogs. Protein expression of SLC22A1, SLC22A3 and SLC29A3 in tumor tissues of patients with pancreatic carcinoma was observed by immunoblotting for the first time. Finally, SLC levels were not found to be associated with KRAS mutation status in exon 2. This study identified a number of associations of transcript levels of SLCs with prognosis of pancreatic cancer patients.