Abstract
BackgroundSodium glucose transporters (SGLTs) play vital roles in glucose uptake in many solid cancers, including pancreatic cancer (PC). However, their expression profile in pancreatic cancer and correlation with prognosis are not clear. Thus, we aimed to analyse the expression profile and prognostic significance of SGLT-1 and SGLT-2 in PC.MethodsEighty-eight patients with pancreatic ductal adenocarcinoma (PDAC) undergoing surgery in Huashan Hospital, Fudan University, from July 2017 to June 2020 were enrolled in the study. Specimens for immunohistochemistry were obtained through surgical resection. Bioinformatics analysis was performed based on the Gene Expression Omnibus (GEO), Oncomine and The Cancer Genome Atlas (TCGA) databases. The statistics were calculated using IBM SPSS Statistics, version 20 and R 4.1.1. P values lower than 0.05 were considered to indicate statistical significance.ResultsSGLT-1 but not SGLT-2 was significantly overexpressed in PDAC. Survival analysis showed that the median overall survival (OS) and progression-free survival (PFS) of patients with high SGLT-1 expression were significantly longer than that of patients with low SGLT-1 expression. Cox regression indicated that high SGLT-1 expression was an independent predictor for a better prognosis, while residual tumour status (R1 and R2) was an independent risk factor for a poor prognosis. Finally, PDZK1-interacting protein 1 (PDZK1IP1), a protein participating in the generation of reactive oxygen species, was overexpressed in PDAC and its expression was significantly correlated with SGLT-1.ConclusionsSGLT-1 but not SGLT-2 was overexpressed in PDAC, and the overexpression of SGLT-1 could be a predictor of a better prognosis. Residual tumour status (R1 and R2) was a risk factor for poor prognosis and disease progression.
Highlights
Pancreatic ductal adenocarcinoma (PDAC), accounting for 90% of pancreatic cancer (PC) cases, is the seventh leading cause of cancer deaths [1, 2]
To study the mechanisms of glucose ingestion by PC tumour cells and explore novel effective targets for PC diagnosis and treatment, we examined the expression profile and survival relevance of Sodium-dependent glucose transporters (SGLTs) in PC and elucidated the specific prognostic significance of SGLT-1, in contrast to glucose transporter 1 (GLUT-1), which has been reported to be correlated with a poor prognosis
Because positive SGLT-2 expression was not found in PDAC samples, we investigated the association between the expression level of SGLT-1 and clinicopathological characteristics, including age (< 64 and ≥ 64 years old), sex, lymph node metastasis (< 1, ≤1 and < 4, and ≥ 4), tumour size (≤4 cm and > 4 cm), TNM stage (I–II and III), tumour pathological grade (I–II, III and IV), SMA/SMV invasion, and diabetes history
Summary
Pancreatic ductal adenocarcinoma (PDAC), accounting for 90% of pancreatic cancer (PC) cases, is the seventh leading cause of cancer deaths [1, 2]. The increased uptake and metabolism of glucose is an important hallmark of cancer [3,4,5]. PDAC is a remarkably stroma-rich, vascular-poor, hypoperfused tumour, leading to deficient drug delivery, which is the main cause of drug resistance. It is possible to explore novel targets in the process of glucose uptake and metabolism in PDAC. Sodium glucose transporters (SGLTs) play vital roles in glucose uptake in many solid cancers, including pancreatic cancer (PC). Their expression profile in pancreatic cancer and correlation with prognosis are not clear. We aimed to analyse the expression profile and prognostic significance of SGLT-1 and SGLT-2 in PC
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
