Bioinformatic Analysis of The Prognostic Value of A Panel of Six Amino Acid Transporters in Human Cancers

Document Type : Original Article


1 Department of Pathology, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China

2 National Clinical Research Center for Cancer, Tianjin, China

3 Key Laboratory of Cancer Prevention and Therapy (Tianjin), Tianjin, China

4 Tianjin's Clinical Research Center for Cancer, Tianjin, China

5 Department of Pathology, Tianjin Medical University Cancer Institute & Hospital, Tianjin, China


Objective: Solid tumor cells utilize amino acid transporters (AATs) to increase amino acid uptake in response to
nutrient-insufficiency. The upregulation of AATs is therefore critical for tumor development and progression. This study
identifies the upregulated AATs under amino acid deprived conditions, and further determines the clinicopathological
importance of these AATs in evaluating the prognosis of patients with cancers.
Materials and Methods: In this experimental study, the Gene Expression Omnibus (GEO) datasets (GSE62673,
GSE26370, GSE125782 and GSE150874) were downloaded from the NCBI website and utilized for integrated
differential expression and pathway analysis v0.96, Gene Set Enrichment Analysis (GSEA), and REACTOME analyses
to identify the AATs upregulated in response to amino acid deprivation. In addition, The Cancer Genome Atlas (TCGA)
datasets with prognostic information were assessed and employed to evaluate the association of identified AATs with
patients’ prognoses using SurvExpress analysis.
Results: Using analysis of NCBI GEO data, this study shows that amino acid deprivation leads to the upregulation
of six AAT genes; SLC3A2, SLC7A5, SLC7A1, SLC1A4, SLC7A11 and SLC1A5. GSEA and REACTOME analyses
identified altered signaling in cells exposed to amino acid deprivation, such as pathways related to stress responses,
the cell cycle and apoptosis. In addition, Principal Component Analysis showed these six AAT genes to be well divided
into two distinct clusters in relation to TCGA tumor tissues versus normal counterparts. Finally, Log-Rank analysis
confirmed the upregulation of this panel of six AAT genes is correlated with poor prognosis in patients with colorectal,
esophageal, kidney and lung cancers.
Conclusion: The upregulation of a panel of six AATs is common in several human cancers and may provide a valuable
diagnostic tool to evaluate the prognosis of patients with colorectal, esophageal, kidney and lung cancers.


Main Subjects

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