Evaluating Distribution and Prognostic Value of New Tumor-Infiltrating Lymphocytes in HCC Based on a scRNA-Seq Study With CIBERSORTx

Abstract

Hepatocellular carcinoma (HCC) is a commonly diagnosed cancer with high mortality rates. The immune response plays an important role in the progression of HCC. Immunotherapies are becoming an increasingly promising tool for treating cancers. Advancements in scRNA-seq (single-cell RNA sequencing) have allowed us to identify new subsets in the immune microenvironment of HCC. Yet, distribution of these new cell types and their potential prognostic value in bulk samples from large cohorts remained unclear. This study aimed to investigate the tumor-infiltration and prognostic value of new cell subsets identified by a previous scRNA-seq study in a TCGA HCC cohort using CIBERSORTx, a machine learning method to estimate cell proportion and infer cell-type-specific gene expression profiles. We observed different distributions of tumor-infiltrating lymphocytes between tumor and normal cells. Among these, the CD4-GZMA cell subset showed association with prognosis (log-rank test, p < 0.05). We further analyzed CD4-GZMA cell specific gene expression with CIBERSORTx, and found 19 prognostic genes (univariable cox regression, p < 0.05). Finally, we applied Least absolute shrinkage and selection operator (LASSO) Cox regression to construct an immune risk score model and performed a prognostic assessment of our model in TCGA and ICGC cohorts. Taken together, the immune landscape in HCC bulk samples may be more complex than assumed, with heterogeneity and different tumor-infiltration relative to scRNA-seq results. Additionally, CD4-GZMA cells and their characteristics may yield therapeutic benefits in the immune treatment of HCC.

ALYREF associated with immune infiltration is a prognostic biomarker in hepatocellular carcinoma

“…Since the abundance and activity of TILs can affect the survival time of patients with various tumors [ 17 , 18 ], we evaluated the correlation of ALYREF with TILs by TIMER and TISIDB. In TIMER, ALYREF was found to be positively linked with the level of immune cell subset infiltration.…”

A novel prognostic model based on single-cell RNA sequencing data for hepatocellular carcinoma

“…Unfortunately, scRNA-seq is relatively expensive, so only a limited number of sample datasets were available. However, the information from scRNA-seq can be very meaningful for exploring the characteristics of each cell subpopulation from bulk samples and the interaction of each cell in the TIME [ 15 – 17 ].…”

NOL12 as an Oncogenic Biomarker Promotes Hepatocellular Carcinoma Growth and Metastasis

“…Some studies have shown that, when all kinds of immune cells in the TME reach a certain balance, they will spur immune activation, thus promoting the occurrence of immune escape [ 18 ]. Increasing evidence has shown that tumor-infiltrating immune cells (TICs) affect the biological behavior of HCC cells and ultimately affect the prognosis of patients [ 19 , 20 ]. In addition, the results of some latest clinical trials and medical studies showed that immunotherapy or combined with immunotherapy was more beneficial to patients with advanced HCC [ 21 , 22 ].…”