The hub ten gene-based risk score system using RNA m⁶A methylation regulator features and tumor immune...

RNA N⁶-methyladenosine (m⁶A) modification is primarily regulated by m⁶A regulators, which play significant epigenetic regulatory roles in tumorigenesis, tumor development, and tumor immune microenvironment. However, the correlation between m⁶A regulators and immune cell infiltration in breast cancer remains unclear.

In this study, m⁶A modification patterns were evaluated based on 31 m⁶A modification regulators. m⁶A clusters were determined by consensus clustering. Immune landscape and immune cell infiltration subgroups were characterized by m⁶A clusters. Key module and hub genes related to m⁶A regulators and immune infiltration cells were identified by WGCNA. LASSO algorithm was applied to select prognostic signatures. Multivariate Cox regression analysis was applied to assess the prognostic value of gene signatures.

Two distinct m⁶A clusters were determined based on the expression of 31 m⁶A modification regulators and characterized by two tumor immune microenvironment (TIME) immune cell infiltration subgroups. Further, a total of 1971 differentially expressed genes between breast cancer patients and healthy controls were screened, nine modules associated with clinical characteristics of breast cancer patients were identified. Later, one key module and 13 hub genes correlated with m⁶A regulators and immune infiltration cells were identified. LASSO Cox regression analysis selected and constructed a ten-gene prognostic model to build a risk score system for individual breast cancer patient prognosis. The performance of the ten-gene-based risk score system was further validated in an independent dataset with an AUC of 0.659.

This study revealed that m⁶A modification regulators played a significant role in the TIME regulation of breast cancer. The hub ten gene-based risk score system is valuable in predicting the prognosis of breast cancer patients, which may provide potential significance for breast cancer diagnosis, prognosis, and immunotherapy in the future.