SGLT-2 as a potential target in pancreatic cancer: the preliminary clue from The Cancer Genome Atlas data

Wei Qiang; Yuyang Lei; Liyue Yuan; Jia Yuan; Jiaojiao Zhang; Yuanyuan Shan; Hong Tian; Bingyin Shi; Hui Guo

doi:10.21037/jgo-22-900

SGLT-2 as a potential target in pancreatic cancer: the preliminary clue from The Cancer Genome Atlas data

J Gastrointest Oncol. 2022 Oct;13(5):2539-2552. doi: 10.21037/jgo-22-900.

Authors

Wei Qiang^#¹, Yuyang Lei^#², Liyue Yuan^{1

3}, Jia Yuan^{1

4}, Jiaojiao Zhang⁵, Yuanyuan Shan⁶, Hong Tian^{7

8}, Bingyin Shi¹, Hui Guo¹

Affiliations

¹ Department of Endocrinology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
² Department of Cardiovascular Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
³ Department of Internal Medicine, Xi'an Baqiao District People's Hospital, Xi'an, China.
⁴ Emergency Department, Xi'an Hospital of Civil Aviation, Xi'an, China.
⁵ Department of Pathology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁶ Department of Pharmacy, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
⁷ Research Center of Reproductive Medicine, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.
⁸ Department of Human Anatomy, Histology and Embryology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, China.

^# Contributed equally.

Abstract

Background: Sodium-glucose co-transporters-2 (SGLT-2) has been reported as overexpressed in tumors including pancreatic cancer (PC). The aim of this study was to investigate the clinicopathological and prognostic significance, as well as the potential role of SGLT-2 in PC development and progression.

Methods: The expression of SGLT-2 was assessed using The Cancer Genome Atlas (TCGA) PC dataset (179 cases). The overall survival (OS) and disease-free survival (DFS) of PC patients with high and low SLC5A2 expression were compared using the online database Gene Expression Profiling Interactive Analysis (GEPIA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using The Database for Annotation Visualization and Integrated Discovery (DAVID) online tool. The genetic correlations of SLC5A2 genes in different subtypes of PC were analyzed by using cBioPortal and LinkedOmics online databases.

Results: No relationship between SGLT-2 expression and PC risk factors, tumor location, histology grade, or tumor-node-metastasis (TNM) stage was identified. Further, SGLT-2 could not be used as prognosis predictor. The KEGG analyses demonstrated that high SGLT-2 expression is correlated with activation of pathways related with chemical carcinogenesis, energy metabolism and drug metabolism, and the suppression of nucleotide excision repair, messenger RNA (mRNA) surveillance, and cell cycle regulation. Specifically, high SGLT-2 level also coexisted with upregulation of gene symbols for pancreatic progenitor subtype for PC.

Conclusions: There is potential for SGLT-2 as a potential target for PC treatment, and SGLT-2 inhibitors should be further evaluated as a novel therapy in PC.

Keywords: Pancreatic cancer (PC); SGLT-2; SGLT-2 inhibitor; SLC5A2; The Cancer Genome Atlas (TCGA).