This study aims to perform a comprehensive genomic analysis to assess the influence of overexpression of MYO1E in non-small cell lung carcinoma (NSCLC) and whether there are differences in survival and mortality risk in NSCLC patients depending on both DNA methylation and RNA expression of MYO1E. The DNA methylation probe cg13887966 was inversely correlated with MYO1E RNA expression in both LUAD and LUSC subpopulations showing that lower MYO1E RNA expression was associated with higher MYO1E DNA methylation. Late stages of lung cancer showed significantly lower MYO1E DNA methylation and significantly higher MYO1E RNA expression for LUAD but not for LUSC. Low DNA methylation as well as high RNA expression of MYO1E are associated with a shorter median survival time and an increased risk of mortality for LUAD, but not for LUSC. This study suggests that changes in MYO1E methylation and expression in LUAD patients may have an essential role in lung cancer’s pathogenesis. It shows the utility of MYO1E DNA methylation and RNA expression in predicting survival for LUAD patients. Also, given the low normal expression of MYO1E in blood cells MYO1E DNA methylation has the potential to be used as circulating tumor marker in liquid biopsies.

Developing new and effective treatments for patients with metastatic colorectal cancer is crucial, as this condition is the fourth leading cause of cancer-related deaths. The potential of the M51R vesicular stomatitis virus (M51R VSV) as an oncolytic virus for various malignancies, including colorectal cancer, is being explored by our group and others. However, the immune response to this treatment is poorly understood. To address this knowledge gap, we conducted a study using a syngeneic murine model of colorectal cancer by administering M51R VSV at two doses and analyzing the resulting immune response. We found that both doses of M51R VSV induced a robust immune response, with overexpression of genes associated with NK cell function, antigen processing and presentation, and CD8+ T cell phenotype and function. CyTOF analysis showed an increased CD8+ T cell frequency and decreased G-MDSCs and FoxP3+CD25- Treg cells. TCR sequence analysis revealed clonal expansion of a-CT26 CD8+ T cells targeted against tumor-associated antigens, making combination therapy with CAR T cells a promising approach. Our work also suggests that combination therapy with M51R VSV and immune checkpoint inhibitors may be beneficial. These findings provide a strong foundation for advancing M51R VSV-based therapies for metastatic colorectal cancer in a population of patients with limited immunotherapeutic options.