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

  • Haitham Kussaibi
  • Khaled R. Alkharsah
  • Dalal Altamimi
  • Ahmed Alsayyah
  • Maha Abdel Hadi
  • Eman Mohammad Abdullah Alsulami
Preclinical study

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).

Keywords

KAI1 downregulation Metastasis suppressor genes Breast cancer Alternative splicing Splice variant KAI1 expression by IHC 

Notes

Acknowledgements

The authors are grateful to all technicians and specialists of the pathology laboratory at King Fahd Hospital of the University and the IRMC at Imam Abdulrahman Bin Faisal University.

Funding

This Project was funded By Deanship for Scientific Research at Imam Abdulrahman Bin Faisal University (Project Number 2015192).

Compliance with ethical standards

Competing interests

The authors declare that they have no competing interests in the manuscript.

Ethics approval

This project was reviewed and approved at the Imam Abdulrahman Bin Faisal University IRB institutional review board (ethical committee) meeting on Sunday, April 26, 2015. IRB Number: IRB-2015-01-095.

Informed consent

Informed patient consent was waived due to use of archival material of anonymous nature that does not disclose patients identity and because patients are lost to follow up.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Pathology, College of MedicineImam Abdulrahman Bin Faisal University (IAU)DammamSaudi Arabia
  2. 2.Department of Microbiology, College of MedicineImam Abdulrahman Bin Faisal University (IAU)DammamSaudi Arabia
  3. 3.Breast Division, Department of Surgery, College of MedicineImam Abdulrahman Bin Faisal University (IAU)DammamSaudi Arabia
  4. 4.Institute for Research and Medical ConsultationsImam Abdulrahman Bin Faisal University (IAU)DammamSaudi Arabia

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