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01-01-2019 | Preclinical study

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

Authors: Haitham Kussaibi, Khaled R. Alkharsah, Dalal Altamimi, Ahmed Alsayyah, Maha Abdel Hadi, Eman Mohammad Abdullah Alsulami

Published in: Breast Cancer Research and Treatment | Issue 1/2019

Abstract

Purpose

KAI1 (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.

Methods

Expression 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.

Results

Out 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).

Conclusion

Alternative splicing is an important mechanism underlying KAI1 loss of function in breast cancer, and it is associated with bad prognosis (advanced cancer stage).

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Title: Alternative splicing is an important mechanism behind KAI1 loss of function in breast cancer patients from Saudi Arabia
Authors: Haitham Kussaibi
Khaled R. Alkharsah
Dalal Altamimi
Ahmed Alsayyah
Maha Abdel Hadi
Eman Mohammad Abdullah Alsulami
Publication date: 01-01-2019
Publisher: Springer US
Published in: Breast Cancer Research and Treatment / Issue 1/2019
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI: https://doi.org/10.1007/s10549-018-4999-0

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