4.6 Article

Lamprey immunity protein enables detection for bladder cancer through recognizing N-hydroxyacetylneuraminic acid (Neu5Gc)-modified as a diagnostic marker and exploration of its production mechanism

期刊

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2022.04.121

关键词

Bladder cancer; LIP; Neu5Gc; Glycosylation; Glycosyltransferase

资金

  1. National Natural Science Foundation of China [31772884, 32070518]
  2. Liaoning Climbing Scholar
  3. Project of the Educational Department of Liaoning Province [Nos.LJKZ0962, LJ2020012]
  4. Distinguished Professor of Liaoning [X-LYC20 02093]

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Previous studies have shown that Neu5Gc is highly expressed in various types of cancer, but its role in bladder cancer has not been well studied. This study demonstrates that Neu5Gc is increased in bladder cancer and can be detected using the LIP from lamprey. The addition of Neu5Gc to cells also leads to increased gene expression of the Neu5Gc synthesis pathway. These findings provide a new tool for detecting bladder cancer and insights into the abnormal glycosylation process.
Previous studies have demonstrated that Neu5Gc is highly expressed in breast, ovarian, prostate, colon and lung cancers, but not in normal human cells. The presence of Neu5Gc is important for prognosis and is associated with aggressiveness, metastasis, and tumor grade. However, increased Neu5Gc in bladder cancer remains unclear. LIP from lamprey binds the carbohydrate receptor of N-glycolylneuraminic acid (Neu5Gc). The combination of Neu5Gc and LIP suggested that it might be used as a diagnostic tool for the detection of Neu5Gc tumor antigen. Here, the classical animal model of bladder cancer was successfully induced by MNU bladder perfusion. The ELISA results showed that the expression level of Neu5Gc in the urine of normal rats was 94.96 +/- 21.01ng/mg, and that of bladder cancer rats was 158.28 +/- 34.86 ng/mg. In addition, the results of SNA and LIP immunohistochemistry demonstrated the high expression of Neu5Gc in bladder cancer. After the addition of Neu5Gc to BIU-87 and SV-HUC-1 cells, transcriptomic sequencing and real-time quantitative PCR analysis demonstrated that the gene expression of Neu5Gc synthesis pathway was significantly increased. These data suggest that LIP provides a new tool for the detection of biological samples, especially urine from patients with bladder cancer or suspected cancer, and that revealing the mechanism of abnormal glycosylation can provide theoretical basis for clinical studies. (c) 2022 Elsevier Inc. All rights reserved.

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