Abstract
BackgroundRecently, increasing evidence has suggested that Glutamine-fructose-6-phosphate transaminase 2 (GFPT2) is related to carcinogenesis. However, the potential roles of GFPT2 in colon cancer still need to be fully investigated.MethodsWe examined the protein levels of GFPT2 by immunohistochemistry (IHC) in tissues collected from 83 patients with colon cancer. We further detected GFBPT2 protein levels by Western Blot assay. We checked the relationship between GFPT2 expression levels and overall survival (OS), stromal and immune scores and immune components from The Cancer Gene Atlas (TCGA) database. GFBP2-related pathways were validated in the Cancer Cell Line Encyclopedia (CCLE) database. Expression of GFPT2 in single cell subpopulations was calculated from The Tumor Immune Single Cell Center (TISCH). The levels of GFPT2 and drug sensitivity data were performed from CellMiner dataset.ResultsGFPT2 was highly expressed and correlated with poor pathological features in 83 colon cancer patients. Moreover, increased GFPT2 expression was significantly associated with poorer OS in 329 colon adenocarcinoma (COAD) patients. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed the differentially expressed genes of GFPT2 were mostly enriched in focal adhesion, ECM receptor interaction, JAK/STAT signaling pathway and immune related pathways. In addition, GFPT2 expression was correlated with the tumor microenvironment (TME). GFPT2 expression was linked to cancer-associated fibroblasts (CAFs)-associated factors and epithelial-mesenchymal transition (EMT)-related factors. GFPT2 was positively correlated with immunosuppressive cells and regulated immunosuppressive factors and T-cell exhaustion. Finally, our data suggested that the expression of GFPT2 may be a judgment of the sensitivity of a certain class of drugs.ConclusionsOur work reveals the roles of GFPT2 in tumorigenesis, particularly in immune response, TME and drug resistance, which are crucial for the development of customized cancer therapies.
Highlights
Increasing evidence has suggested that Glutamine-fructose-6phosphate transaminase 2 (GFPT2) is related to carcinogenesis
Our results showed that GFPT2 was an oncogene highly expressed in colon cancer tissues compared to paraneoplastic tissues (Figures 1A, B)
The findings indicated that fibroblasts were the major GFPT2 expressing cells, and the expression of GFPT2 was very high in fibroblasts compared to other cell subpopulations (Figure 4C), indicating that GFPT2 has an important function in cancer-associated fibroblasts (CAFs)
Summary
Increasing evidence has suggested that Glutamine-fructose-6phosphate transaminase 2 (GFPT2) is related to carcinogenesis. The potential roles of GFPT2 in colon cancer still need to be fully investigated. Colon cancer is a common malignant tumor of the gastrointestinal tract occurring at the junction of the rectum and sigmoid colon, with the highest incidence in the age group of 40 to 50 years old, and the ratio of men to women is 2 to 3:1 [1]. Colon cancer is the third and second most commonly diagnosed cancer in men and women, respectively, with 1.9 million new cases and nearly 935,000 deaths in 2020 [2]. Metastasis is a characteristic of colon cancer deterioration. Distant metastases from colon cancer are mainly in the liver, and about 50% of patients will have preoperative or postoperative liver metastases. It is crucial to find new treatments for colon cancer
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