CAT and CXCL8 are crucial cofactors for the progression of nonalcoholic steatohepatitis to hepatocellular carcinoma, the immune infiltration and prognosis of hepatocellular carcinoma

Abstract

Purpose

Hepatocellular carcinoma (HCC) is a malignant tumour characterized by high morbidity and mortality. Immunotherapy is an important treatment newly approved for the treatment for advanced hepatocellular carcinoma. However, how NASH progresses to HCC and the association between the immune signature in HCC and patient prognosis remain unclear.

Methods

Data from NASH and NASH-HCC patients were obtained from the GEO database. Differentially expressed genes were screened and hub genes were identified. The enrichment analysis, clustering, cibersort, ssGSEA, Xcell and immune checkpoint expression data of the samples were analysed. Survival analysis of dual genes was performed using TCGA liver cancer samples and the lasso regression model, and Cox regression analysis was conducted. Pathology specimens from 21 NASH-associated hepatocellular carcinoma patients were collected, and immunohistochemical staining was used to verify gene expression.

Results

Compared with HCC patients with high CAT and low CXCL8 expression, those with low CAT and high CXCL8 expression had significantly higher levels of infiltration of multiple immune cell types and the common immune checkpoints CD274, PDCD1 and CTLA4. Furthermore, CAT was a protective factor, and CXCL8 was a risk factor for the prognosis of HCC patients.

Conclusion

CAT and CXCL8 might impact NASH-HCC progression. HCC patients with low CAT and high CXCL8 expression might have more extensive immune cell infiltration and stronger tumour immune escape. However, probably due to their different effects on CD8 + T cells and reactive oxygen species, increased expression of CAT contributes to improved prognosis in HCC patients, whereas increased expression of CXCL8 leads to a poor prognosis.