Deconvolution of bulk gene expression profiles reveals the association between immune cell polarization and the prognosis of hepatocellular carcinoma patients

Background: Many studies have utilized computational methods, including cell composition deconvolution (CCD), to correlate immune cell polarizations with the survival of cancer patients, including those with hepatocellular carcinoma (HCC). However, currently available cell deconvolution estimated (CDE) tools do not cover the wide range of immune cell changes that are known to influence tumor progression. Results: A new CCD tool, HCCImm, was designed to estimate the abundance of tumor cells and 16 immune cell types in the bulk gene expression profiles of HCC samples. HCCImm was validated using real datasets derived from human peripheral blood mononuclear cells (PBMCs) and HCC tissue samples, demonstrating that HCCImm outperforms other CCD tools. We used HCCImm to analyze the bulk RNA-seq datasets of The Cancer Genome Atlas (TCGA)-liver hepatocellular carcinoma (LIHC) samples. We found that the proportions of memory CD8⁺ T cells and Tregs were negatively associated with patient overall survival (OS). Furthermore, the proportion of naïve CD8⁺ T cells was positively associated with patient OS. In addition, the TCGA-LIHC samples with a high tumor mutational burden had a significantly high abundance of nonmacrophage leukocytes. Conclusions: HCCImm was equipped with a new set of reference gene expression profiles that allowed for a more robust analysis of HCC patient expression data. The source code is provided at https://github.com/holiday01/HCCImm.