Expression and Bioinformatics-Based Functional Analysis of UAP1 in Lung Adenocarcinoma

Lung adenocarcinoma (LAD) is the most prevalent type of lung cancer. The abnormal expression of UDP-N-acetylglucosamine pyrophosphorylase 1 (UAP1) has been reported to be involved in many biological processes of cancer cells, but the expression of UAP1 in LAD is unclear.

Bioinformatics was used to analyse the LAD gene expression data and related clinical data in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. DAVID6.8 was used to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) signal pathway enrichment analyses of UAP1 expression-related genes. The STRING database was used to analyse protein-protein interaction (PPI) networks. RNA isolation and reverse transcription-quantitative polymerase chain reaction (RT‑qPCR) assay were used to detect the expression of UAP1 in tissues and blood samples.

We found that UAP1 was upregulated in LAD tissues and correlated with poor clinical outcome. GO analysis showed that these genes were enriched in biological processes and functions including intracellular transport, cellular protein catabolic process, and mitochondria (P<0.05). The KEGG pathway analysis showed that these genes were mainly involved in the signalling pathways of amino sugar and nucleotide sugar metabolism, the aminoacyl-tRNA biosynthesis signalling pathway, and protein export (P<0.05). The PPI analysis showed that EPRS, COPB1, CCT3, ALDH18A1 and ARF1 genes had marked or potential interaction with UAP1 (P<0.01). In addition, UAP1 expression was upregulated in LAD tissues compared to normal tissues. High levels of UAP1 expression were associated with larger tumour sizes and later TNM stages. RT‑qPCR detection in serum further showed that UAP1 expression was upregulated in the plasma of LAD patients compared to that of healthy volunteers. High expression of UAP1 in serum suggests a poor prognosis for LAD patients.

UAP1 could be a novel diagnostic biomarker and a promising therapeutic target for LAD.