J Cancer 2022; 13(8):2540-2558. doi:10.7150/jca.72161 This issue

Research Paper

GLUT1 Regulates the Tumor Immune Microenvironment and Promotes Tumor Metastasis in Pancreatic Adenocarcinoma via ncRNA-mediated Network

Fengjiao Li1,3†, Chong He1,3†, Hanming Yao1,3†, Weiling Liang1,3, Xijiu Ye3,4, Jianmin Ruan1,3, Lijun Lin1,3, Jinmao Zou1,3, Shurui Zhou1,3, Yuzhou Huang1,3, Yaqing Li1,3, Shaojie Chen1,3, Kaihong Huang1,3✉, Guoda Lian1,3✉, Shangxiang Chen1,2,3✉

1. Department of Gastroenterology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
2. Department of Gastrointestinal Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
3. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
4. Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China.
† These authors contributed equally to this work.

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Citation:
Li F, He C, Yao H, Liang W, Ye X, Ruan J, Lin L, Zou J, Zhou S, Huang Y, Li Y, Chen S, Huang K, Lian G, Chen S. GLUT1 Regulates the Tumor Immune Microenvironment and Promotes Tumor Metastasis in Pancreatic Adenocarcinoma via ncRNA-mediated Network. J Cancer 2022; 13(8):2540-2558. doi:10.7150/jca.72161. Available from https://www.jcancer.org/v13p2540.htm

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Abstract

Graphic abstract

Pancreatic adenocarcinoma (PAAD) is a digestive tumor with extremely high malignancy. Previous studies have reported that Glucose transporter 1 (GLUT1) contributes to the aggressive tumor progression in various cancer types and indicates an unfavorable prognosis. However, the function of GLUT1 in PAAD remains largely unclear. Through pan-cancer analysis of GLUT1 expression, GLUT1 expression was significantly higher in several cancer types including PAAD. Survival analysis based on the GLUT1 expression showed that GLUT1 could serve as a predictor of poor prognosis. We further predicted and screened the candidate non-coding RNAs (ncRNAs) upstream of the GLUT1 mRNA through correlation analysis, and found that the CASC19/miR-140-5p axis contributing to the regulation of GLUT1 expression. Our study suggested a link exists between GLUT1 expression and selected immunity-related indicators. Subsequent analysis revealed overexpression of GLUT1 in pancreatic cancer specimens and patients with highly expressed GLUT1 expression had worse prognosis. Based on the significantly different expression of GLUT1, the possibility that GLUT1 participated in tumor progression was identified. Using online public databases, genes co-expressed with GLUT1 were screened and enriched to metastasis-related pathways by enrichment analysis. Additionally, functional assays verified that GLUT1 could function in the metastatic process of PAAD cancer cells. Therefore, we proposed that GLUT1 might serve as a role in tumor immunity and tumor metastasis, and was expected to be a prognostic factor in PAAD.

Keywords: Pancreatic adenocarcinoma, GLUT1, ncRNAs, immune infiltration, metastasis