SLC17A9 Is a Novel Prognostic Biomarker Correlated With Immune Infiltrates in Human Lung Adenocarcinoma and Lung Squamous Cell Carcinoma

Background: Overexpression of vesicular nucleotide transporter (SLC17A9) has been found in different types of cancers. Nonetheless, little is known about its influence on lung cancers including human lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Methods Integrative analysis of SLC17A9 and other solute carrier family 17 genes (SLC17A1-8) was performed in patients with LUAD and LUSC based on The Cancer Genome Atlas database. Real-time PCR, western blots, MTS assay, EdU assay, ATP production assays and cell cycle analysis were applied to determine the effect and mechanism of SLC17A9 knockdown in LUAD cells. Results Compared with normal tissue, two SLC17 genes (SLC17A5 and SLC17A9) exhibited a distinctly different expression pattern in LUAD and LUSC. The expression of SLC17A3/7/8/9 expression was significantly correlated with worse overall survival ( p  < 0.05) in LUAD. Conversely, SLC17A1/2/4/6/9 expression was correlated with poorer OS ( p  < 0.05) in LUSC. ROC analysis suggested that the area under the curve of most SLC17 family genes was higher than 0.5. Meanwhile, multiple types of genetic alterations in SLC17 family genes were observed in tumor samples. Gene set enrichment analysis GSEA and protein-protein interaction results revealed that oncogenic signaling pathways and biological regulation, metabolic process, hallmark of myc targets, DNA repair, coagulation and complement were linked to SLC17A9 upregulation. Moreover, SLC17A9 knockdown significantly inhibited cell proliferation and ATP levels by affecting Myc, MFN2, STAT3, Cytochrome C and P2X1 expression in A549 cells. Specifically, SLC17A9 expression correlated negatively with overall survival and positively with most LUSC immune cells. SLC17A9 expression has correlations with infiltrating levels of B cells, CD4 + T cells, M1 macrophages, natural killer cells, Th1, Th2, Tfh, Th17 and Treg cells, as well as PD-1, CTLA4, and LAG3 of T cell exhaustion in LUAD. Conclusions Together, SLC17A9 could potentially serve as a prognostic biomarker correlated with immune infiltrates in LUAD and LUSC.