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

Haitham Kussaibi1, Khaled R Alkharsah2,3, Dalal Altamimi4

  • 1Department of Pathology, College of Medicine, Imam Abdulrahman Bin Faisal University (IAU), Dammam, Saudi Arabia. hkussaibi@iau.edu.sa.

Breast Cancer Research and Treatment
|October 12, 2018
PubMed
Abstract

Insights

Alternative splicing causes loss of KAI1 (CD82) function in breast cancer, linked to advanced stages and poor prognosis. This study identified truncated-KAI1 in 22% of samples, correlating with metastasis.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • KAI1 (CD82) is a metastasis suppressor gene frequently downregulated in breast cancer.
  • Loss of KAI1 function is associated with poor prognosis in various solid tumors.
  • The precise mechanisms behind KAI1 downregulation remain complex and require further investigation.

Purpose of the Study:

  • To investigate alternative splicing as a mechanism for KAI1 loss of function in breast cancer patients.
  • To analyze KAI1 expression patterns in breast cancer tissues from Saudi Arabia.

Main Methods:

  • Immunohistochemistry (IHC) was used to assess KAI1 expression in FFPE breast cancer tissues.
  • Two antibodies, TS82B (extracellular domain) and EPR4112 (C-terminal domain), were employed to detect full-length and truncated KAI1.
  • Expression levels were correlated with clinical parameters, including cancer stage and lymph node metastasis.

Main Results:

  • 67% of 90 breast cancer samples exhibited loss of KAI1 expression.
  • Full-length KAI1 was detected in 33% of samples (TS82B antibody).
  • Truncated-KAI1 (detected by EPR4112 antibody) was found in 22% of samples, significantly correlating with advanced cancer stage and lymph node metastasis (P=0.008).

Conclusions:

  • Alternative splicing is a significant mechanism contributing to KAI1 loss of function in breast cancer.
  • The presence of truncated-KAI1 is associated with advanced disease stage and suggests a poor prognosis.
  • These findings highlight the clinical relevance of alternative splicing in breast cancer progression.
Keywords:
Alternative splicingBreast cancerKAI1 downregulationKAI1 expression by IHCMetastasis suppressor genesSplice variant

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