Abstract

A growing amount of evidence has suggested the clinical importance of stromal and immune cells in the liver cancer microenvironment. However, reliable prognostic signatures based on assessments of stromal and immune components have not been well-established. This study aimed to identify stromal-immune score–based potential prognostic biomarkers for hepatocellular carcinoma. Stromal and immune scores were estimated from transcriptomic profiles of a liver cancer cohort from The Cancer Genome Atlas using the ESTIMATE (Estimation of STromal and Immune cells in MAlignant Tumors using Expression data) algorithm. Least absolute shrinkage and selection operator (LASSO) algorithm was applied to select prognostic genes. Favorable overall survivals and progression-free interval were found in patients with high stromal score and immune score, and 828 differentially expressed genes were identified. Functional enrichment analysis and protein–protein interaction networks further showed that these genes mainly participated in immune response, extracellular matrix, and cell adhesion. MMP9 (matrix metallopeptidase 9) was identified as a prognostic tumor microenvironment–associated gene by using LASSO and TIMER (Tumor IMmune Estimation Resource) algorithms and was found to be positively correlated with immunosuppressive molecules and drug response.

Highlights

  • Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide

  • Using the ESTIMATE algorithm, we revealed the correlation between the immune-stromal scores and the clinical HCC

  • By analyzing the correlation between the immune scores and tumor recurrence, our data show that high-immune-score patients have a longer progression-free interval (PFI) and overall survival (OS) rates, indicating that the tumor microenvironment (TME) composition affects the clinical outcomes of HCC patients, which is consistent with previous studies (Haider et al, 2020)

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Summary

Introduction

Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. The median survival of HCC patients in China is about 23 months, and ≥ 60% of patients present with intermediate-stage or advanced-stage HCC (Kanwal and Singal, 2019; Yang et al, 2019). The main treatment for HCC patients in early stages is surgery, combination with transarterial chemoembolization, ablation, and liver transplantation. For others in advanced stages, the effective approaches involve molecular targeting agents (sorafenib, lenvatinib, and regorafenib). Stromal-Immune Score in HCC these methods have improved the prognosis of HCC patients, the overall survival (OS) of HCC remains challenging for the heterogeneity of HCC. There is still a lack of molecular markers used in determination of prognosis and treatment for patients (Bruix et al, 2016)

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