Comprehensive Analysis of Ferritin Subunits Expression and Positive Correlations with Tumor-Associated Macrophages and T Regulatory Cells Infiltration in Most Solid Tumors.

Ferritin is the most important iron storage form and is known to influence tumor immunity. We previously showed that expression of ferritin light chain (FTL) and ferritin heavy chain (FTH1) subunits is increased in head and neck squamous cell carcinoma (HNSC). Here, we analyzed solid tumor datasets from The Cancer Genome Atlas and Genotype-Tissue Expression databases to investigate correlations between FTL and FTH1 expressions and (i) patient survival, using univariate, multivariate, Kaplan-Meier and Receiver Operator Characteristic analysis; and (ii) tumor-infiltrating immune cell subsets, using the bioinformatics tools Estimation of Stomal and Immune cells in Malignant Tumor tissues, Microenvironment Cell Population-counter, Tumor Immune Estimation Resource, and Tumor Immunology Miner. We found that FTL and FTH1 are upregulated and downregulated, respectively, in most of the human cancers analyzed. Tumor FTL levels were associated with prognosis in patients with lower grade glioma (LGG), whereas FTH1 levels were associated with prognosis in patients with liver hepatocellular carcinoma, HNSC, LGG, and kidney renal papillary cell carcinoma. In many cancers, FTL and FTH1 levels was significantly positively correlated with tumor infiltration by tumor-associated macrophages and T regulatory cells. These results suggest an important role for FTL and FTH1 in regulating tumor immunity to solid cancers.