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


METHODS
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.


RESULTS
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.


CONCLUSIONS
This study identified a number of associations of transcript levels of SLCs with prognosis of pancreatic cancer patients.
Toxicogenomics Unit, National Institute of Public Health, Srobarova 48, Prague 10, Czech Republic. D.Beatrice@seznam.cz
Beatrice
B
Mohelnikova-Duchonova
Veronika
V
Brynychova
Viktor
V
Hlavac
Matej
M
Kocik
Martin
M
Oliverius
Jan
J
Hlavsa
Eva
E
Honsova
Jan
J
Mazanec
Zdenek
Z
Kala
Bohuslav
B
Melichar
Pavel
P
Soucek
D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics / Q000473:pathology*; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D009154:Mutation; D027701:Organic Cation Transport Proteins / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D011379:Prognosis; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D015996:Survival Rate; D015854:Up-Regulation; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D026901:Membrane Transport Proteins; D027701:Organic Cation Transport Proteins; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins