High expression of IL4I1 is correlated with poor prognosis and immune infiltration in thyroid cancer

Thyroid cancer-related deaths mostly result from metastasis. It was reported that the immunometabolism associated enzyme interleukin-4-induced-1 (IL4I1) was related to tumor metastasis. The present study was intended to investigate the effects of IL4I1 on thyroid cancer metastasis and its relationship with the prognosis.

Data from Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were analyzed to find out the different mRNA expressions of IL4I1 between thyroid cancer and normal tissues. And Human Protein Atlas (HPA) was used to assess IL4I1 protein expression. To further differentiate thyroid cancer from normal tissues and estimate the impact of IL4I1 on the prognosis, the receiver operating characteristic curve (ROC) and Kaplan-Meier (KM) method was performed. The protein-protein interaction (PPI) network was established using STRING, and functional enrichment analyses were conducted by "clusterProfiler" package. Then, we assayed the correlation between IL4I1 and some related molecules. The relationship between IL4I1 and immune infiltration was performed using "Gene Set Variation Analysis (GSVA)" package in TCGA and tumor-immune system interaction database (TISIDB). Finally, we did in vitro experiments in order to further prove the bioeffects of IL4I1 on metastasis.

The expression of IL4I1 mRNA and IL4I1 protein was significantly upregulated in thyroid cancer tissues. The increment of IL4I1 mRNA expression was related to high-grade malignancy, lymph node metastases and extrathyroidal extension. The ROC curve displayed the cutoff value of 0.782, with the sensitivity of 77.5% and the specificity of 77.8%. KM survival analysis showed that there was a worse PFS in patients with high IL4I1 expression than those with low IL4I1 expression (p = 0.013). Further study indicated that IL4I1 was associated with lactate, body fluid secretion, positive regulation of T cell differentiation, and cellular response to nutrients in Gene Ontology (GO) analysis. Moreover, IL4I1 was found correlated with immune infiltration. Finally, the in vitro experiments revealed the promotion of IL4I1 on cancer cell proliferation, migration and invasion.

The increased IL4I1 expression is markedly correlated with the immune imbalance in the tumor microenvironment (TME) and predicts poor survival in thyroid cancer. This study reveals the potential clinical biomarker of poor prognosis and the target of immune therapy in thyroid cancer.