KIT Mutations Correlate with Higher Galectin Levels and Brain Metastasis in Breast and Non-Small Cell Lung Cancer

Cancers (Basel). 2022 Jun 3;14(11):2781. doi: 10.3390/cancers14112781.

Abstract

To investigate a potential role for galectins as biomarkers that enable diagnosis or prognostication of breast or non-small cell lung cancer, the serum levels of galectins -1, -3, -7, -8, and -9 of cancer patients determined by ELISA assays were compared to the mutation status of 50 known cancer-critical genes, which were determined using multiplex PCR in tumors of the same patients. Mutations in the KIT proto-oncogene, which codes for the c-Kit protein, a receptor tyrosine kinase, correlated with higher levels of galectins -1, -3, -8, and -9 in breast cancer patients and galectin-1 in non-small cell lung cancer patients. Mutations in the KIT gene were more likely found in brain metastases from both of these primary cancers. The most common KIT mutation in our panel was p.M541L, a missense mutation in the transmembrane domain of the c-Kit protein. These results demonstrate an association between KIT oncogenic signaling and elevated serum galectins in patients with metastatic disease. Changes in protein trafficking and the glycocalyx composition of cancer cells may explain the observed alterations in galectin expression. This study can be useful for the targeted selection of receptor tyrosine kinase and galectin inhibitor anti-cancer treatments.

Keywords: CD117; ELISA; KIT gene; breast cancer; c-Kit; cancer hotspot panel; galectin; mutation; non-small cell lung cancer.

Grants and funding

This research was funded by the Prisma Health Cancer Institute Philanthropy Grant and Sargent Foundation. The APC was funded by the Biomedical Sciences Department at the University of South Carolina School of Medicine Greenville.