MUC5B mutation

Together, our findings establish the immunogenicity and therapeutic potential of mutant MUC family-derived neoantigens. Through combining the tools of TSNAdb and DAI, a group of novel MUCmut neoantigens were identified as potential targets for immunotherapy.

Our identification of an increased prevalence of clonal somatic mutation in diseased lungs that correlates with airway epithelial gene expression and disease severity highlights for the first time the role of somatic mutational processes in lung disease genetics.

Enriched pathway analyses showed that cancer-related pathways, including immune-related pathways, were significantly activated in high-score samples and that some drugs have significantly lower IC values than those with low score. The model developed based on immune-related genes is robust and reflected various statuses of CRC and may be a potential clinical indicator.

Our study concludes by highlighting the functional role of O-glycosylated and mutant MUC5B in promoting LUAD by immune suppression. Further, clinical gene expression validation of MUC5B suggests its potential role as a diagnostic biomarker for LUAD metastasis.

Our findings revealed potential genetic regulators to predict the castration resistance and provide insights into the castration resistance processes in advanced prostate cancer. The crosstalk between clonal evolution patterns and tumor microenvironment may also play a role in castration resistance. A multicenter-research including larger populations with different background are needed to confirm our conclusion in the future.

These results suggest that the presence of MUC5B mutation correlates with more potent anti-tumor efficacy of ATG-008, potentially serving as a positive predictive biomarker for patient enrichment that warrants further investigation in the clinic.