Abstract
Keratan sulfate (KS) is a sulfated linear polymer of N-acetyllactosamine. Proteoglycans carrying keratan sulfate epitopes were majorly observed in cornea, cartilage and brain; and mainly involved in embryonic development, cornea transparency, and wound healing process. Recently, expression of KS in cancer has been shown to be highly associated with advanced tumor grade and poor prognosis. Therefore, we aimed to identify the expression of KS epitope in human pancreatic cancer primary and metastatic tumor lesions. Immunohistochemical analysis of KS expression was performed on primary pancreatic tumors and metastatic tissues. We observed an increased expression of KS epitope on primary tumor tissues compared to uninvolved normal and tumor stroma; and is associated with worse overall survival. Moreover, lung metastatic tumors show a higher-level expression of KS compared to primary tumors. Interestingly, KS biosynthesis specific glycosyltransferases expression was differentially regulated in metastatic pancreatic tumors. Taken together, these results indicate that aberrant expression of KS is predictive of pancreatic cancer progression and metastasis and may serve as a novel prognostic biomarker for pancreatic cancer.
Highlights
Stromal tissues in lung and liver metastases have low Keratan sulfate (KS) expression compared to tumor cells (Supplemental Fig. S2B). These results indicate that higher levels of KS expression are associated with pancreatic cancer metastasis, preferably to lung tissues
We showed for the first time the correlation of aberrant KS expression with pancreatic cancer progression and metastasis and with worse overall patient survival status
This study revealed a higher-level expression of KS in primary pancreatic tumor, and even increased in lung metastatic deposits and associated with worse patient survival
Summary
We aimed to identify the expression of KS epitope in human pancreatic cancer primary and metastatic tumor lesions
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