Abstract
Abstract Introduction hCNT (Human Concentrative Nucleoside Transporter, also known as SLC28A1) and hENT (Human Equilibrative Nucleoside Transporter, SLC29A1) belong to the large solute carrier (SLC) family, a large membrane transport molecule group for the influx and efflux across cell membrane of various solutes including some of the anticancer drugs. hCNT and hENT are suggested to be involved in the transportation of certain chemotherapeutic drugs. The present study investigated the role of both transporters in gastric cancer and the response of gastric cancer cell and patients to chemotherapeutic drugs. Methods The expression levels of hCNT and hENT gene transcripts and proteins were determined in two independent gastric cancer cohorts and assessed against patient's responses to neoadjuvent chemotherapies. Their value in assessing patient's survival, clinical and pathological indicators was also assessed. Results Gastric tumour tissues expressed significantly higher levels of hCNT and hENT than normal stomach tissues (p=0.022 and p=0.0071, respectively for hCNT and hENT). Expression levels of the hCNT and hENT gene transcripts presented significant correlation with the overall survival (OS) (Hazard Ration (HR)=2.885, p<0.001 for hCNT; HR=2.078, p<0.001 for hENT) and disease-free survival of the patients (HR=2.434, p=0.004 for hCNT; HR=2.072, p<0.001). Patients with high levels of hCNT in their gastric tumours were more resisted to neoadjuvant therapies (HR=3.437, p=0.013, by ROC model), although the same was not seen with hENT. Conclusion hCNT and hENT have significant prognostic factors for patients with gastric cancer and theranostic factor for response to neoadjuvant therapies.
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