Alternative splicing is an important mechanism behind KAI1 loss of function in breast cancer patients from Saudi Arabia

PurposeKAI1 (also called CD82) is a metastasis suppressor gene known to be downregulated in breast cancer and other solid tumors. The downregulation of KAI1 or loss of its function is usually associated with bad prognosis. The mechanism behind KAI1 loss of function is complex. In this study, we investigated alternative splicing as a possible mechanism that underlies KAI1 loss of function in breast cancer patients from a tertiary hospital in Saudi Arabia.MethodsExpression of KAI1 was studied in FFPE breast cancer and control tissue sections by IHC using two different antibodies targeting different domains of the protein. The TS82B antibody targets the extracellular loop, which constitutes most of the protein, while the second EPR4112 antibody targets the C-terminal intracellular domain of the protein.ResultsOut of 90 breast cancer samples, 67% showed loss of KAI1 expression. The remaining 33% showed KAI1 expression with (TS82B) antibody; however, the protein was detected in only 11% of cancers when using the antibody (EPR4112) indicating a truncation of the protein at the C-terminus (truncated-KAI1) in 22% of the studied cancer samples. A significant correlation was found between truncated-KAI1 expression and advanced cancer stage (association with lymph node metastasis, P value 0.008).ConclusionAlternative splicing is an important mechanism underlying KAI1 loss of function in breast cancer, and it is associated with bad prognosis (advanced cancer stage).