Background:
Immunotherapy elicits durable responses in many
tumors. Nevertheless, the positive response to
immunotherapy always depends on the dynamic interactions between the
tumor cells and infiltrating lymphocytes in the tumor microenvironment (TME). Currently, the application of
immunotherapy in
hepatocellular carcinoma (HCC) has achieved limited success. The ectopic modification of
N6-methyladenosine (m6A) is a common feature in multiple
tumors. However, the relationship between
m6A modification with HCC clinical features, prognosis, immune cell infiltration, and
immunotherapy efficacy remains unclear. Materials and Methods: Here, we comprehensively evaluated
m6A modification clusters based on 22
m6A regulators and systematically explored the relationship between
m6A modification with
tumor progression, prognosis, and immune cell infiltration characteristics. The m6Ascore was calculated by principal component analysis to quantify the
m6A modifications of individual patients. Key regulators involved in immunoregulation in HCC were identified using immunohistochemistry and immunofluorescence. Results: Three distinct
m6A modification clusters were identified. The
m6A clusters were significantly associated with clinical features, prognosis, and immune cell infiltration. The three clusters were highly consistent with the three
tumor immune phenotypes, i.e., immune-excluded, immune-inflamed, and immune-desert. Comprehensive bioinformatics analysis revealed that high m6Ascore was closely associated with
tumor progression, poor prognosis, and
immunotherapy non-response.
m6A regulators were dysregulated in HCC tissues. Hence, they play a role as predictors of poor prognosis. Tissue microarray demonstrated that overexpressed YTHDF1 was associated with low CD3+ and CD8+ T cell infiltration in HCC. Conclusion: Our findings demonstrate that
m6A modification patterns play a crucial role in the
tumor immune microenvironment and the prognosis of HCC. High YTHDF1 expression is closely associated with low CD3+ and CD8+ T cell infiltration in HCC.