A novel prognostic signature and therapy guidance for hepatocellular carcinoma based on STEAP family

Abstract

Background: The six-transmembrane epithelial antigen of prostate (STEAP) family members are known to be involved in various tumor-related biological processes and showed its huge potential role in tumor immunotherapy.

Methods: Biological differences were investigated through Gene set enrichment analysis (GSEA) and tumor microenvironment analysis by CIBERSORT. Tumor mutation burden (TMB), immunotherapy response and chemotherapeutic drugs sensitivity were estimated in R.

Results: We established a prognostic signature with the formula: risk score = STEAP1 × 0.3994 + STEAP4 × (- 0.7596), which had a favorable concordance with the prediction. The high-risk group were enriched in cell cycle and RNA and protein synthesis related pathways, while the low-risk group were enriched in complement and metabolic related pathways. And the risk score was significantly correlated with immune cell infiltration. Most notably, the patients in the low-risk group were characterized with increased TMB and decreased tumor immune dysfunction and exclusion (TIDE) score, indicating that these patients showed better immune checkpoint blockade response. Meanwhile, we found the patients with high-risk were more sensitive to some drugs related to cell cycle and apoptosis.

Conclusions: The novel signature based on STEAPs may be effective indicators for predicting prognosis, and provides corresponding clinical treatment recommendations for HCC patients based on this classification.

Keywords: Drug sensitivity; Hepatocellular carcinoma; Immunotherapy; Prognosis signature; STEAP.

Fig. 1

Identification of differentially expressed and prognostic-related STEAPs in the TCGA cohorts. A Violin plots showed the expression profile of STEAP family in HCC tumor tissues and normal tissues. B Survival analysis of STEAP family related signatures. **P < 0.01

Fig. 2

The validation of the prognostic risk model and the nomogram and calibration curve of the model in the TCGA cohorts. A Kaplan–Meier survival curves based on risk score. B 0.5-, 1-, and 3-year ROC curves based on risk score. C Nomogram for predicting overall survival. D The calibration curves for 1-, 3-, and 5-year OS

Fig. 3

Differential expression of AFP between two groups and functional enrichment analysis of the two groups. A, B Boxplot showed that the expression of AFP at high-risk group is significantly higher than that at low-risk group in the (A) TCGA and (B) GSE14520 cohorts. C, D The GSEA analysis for TCGA (C) and GSE14520 (D). **P < 0.01

Fig. 4

Immune signature in two groups. A, B discrepancy analysis of tumor-infiltrating immune cells between two groups in the (A) TCGA and (B) GSE14520 cohorts

Fig. 5

TMB analysis, immunotherapy response, and therapeutic drug sensitivity prediction. A OncoPrint of frequently mutated genes in high- and low-risk groups. B TMB difference between high- and low-risk groups. C TIDE score between two groups. D chemotherapeutic drugs with significant IC50 differences between the two groups