Pan-cancer TCGA analysis reveals the potential involvement of B-type lamins in dysregulating chromosome segregation in human cancer.

Abstract

Lamins play a crucial role in maintaining nuclear structure and function. Our study investigates the expression patterns and clinical implications of B-type lamins with a special focus on lamin B2 across various cancer types using comprehensive RNA sequencing datasets. We found that high expression levels of lamin B1 and lamin B2 are associated with decreased overall and disease-free survival in cancer. This association is further pronounced when both lamins are co-expressed, indicating a compounded negative impact on patient prognosis. Additionally, we highlighted the relationship between B-type lamins and the tumor microenvironment. Lamin B1 mRNA expression shows a strong positive correlation with activated CD4⁺ T-cells and type 2 T-helper cells (Th2), suggesting its role in immune cell infiltration and response within tumors. Lamin B2 expression also correlates moderately with these immune cells, indicating a potential but lesser role in modulating the immune landscape. Notably, the epigenetic state of lamin B1 significantly affects the tumor microenvironment, suggesting a dual role in structural integrity and immune modulation. We have identified 9 lamin B2 interacting proteins that are co-expressed with B-type lamins in cancerous conditions and modulate cytokinesis and cell division pathways during tumorigenesis. Furthermore, we have identified specific molecular targets of B-type lamins that co-express with them in a range of human cancers and are potentially involved in dysregulating chromosome segregation and mRNA binding. Overexpression of these targets alongside B-type lamins correlates with poor prognosis in multiple cancers. These findings underscore the potential of B-type lamins as biomarkers for poor prognosis and as targets for cancer therapies.