Identification of the alpha linolenic acid metabolism-related signature associated with prognosis and the immune microenvironment in nasopharyngeal carcinoma

Abstract

Background: Tumor metabolism is important for cancer progression. Nevertheless, the role of the metabolism pathway and related molecules in nasopharyngeal carcinoma (NPC) is limited.

Methods: Open-accessed data was downloaded from The Cancer Genome Atlas database. All the analysis was performed using the R software and the package in R environments.

Results: In our study, we firstly explored the role of 21 metabolism-related pathways in NPC patients. We found that the steroid biosynthesis and biosynthesis of unsaturated fatty acids were risk factors, while the alpha linolenic acid metabolism was a protective factor. Then, the alpha linolenic acid metabolism aroused our interest. A total of 128 differentially expressed genes (DEGs) were identified, including 71 downregulated and 57 upregulated genes identified between high and low alpha linolenic acid metabolism level. Based on these DEGs, we constructed a prognosis model including DEFB4B, FOXL2NB, MDGA2, RTL1, SLURP2, TMEM151B and TSPAN19, which showed great prediction efficiency in both training and validation cohorts. Clinical correlation analysis showed that high-risk patients might have worse clinical pathology parameters. Pathway enrichment analysis showed that riskscore was positively correlated with angiogenesis, DNA repair, G2/M checkpoints, IL6/JAK/STAT3 signaling, KRAS signaling up, WNT beta-catenin signaling, PI3K/AKT/mTOR signaling, yet positively correlated with inflammatory response, xenobiotic metabolism, TNF-α signaling via NFKB and interferon-gamma response. Immune infiltration analysis showed that the riskscore was positively correlated with the M2 and M0 macrophages, but negatively correlated with neutrophils, plasma cells, follicular helper T cells and resting dendritic cells Moreover, we found that the low-risk patients might be more sensitive to immunotherapy and lapatinib.

Conclusions: In all, our study identified the genes associated with alpha linolenic acid metabolism and constructed an effective prognosis model which could robustly predict NPC patients prognosis.

Keywords: immune; immunotherapy; metabolism; nasopharyngeal carcinoma; prognosis.