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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Prognostic relevance of LGALS3BP in human colorectal carcinoma
Enza Piccolo1, Nicola Tinari2,3, Domenica D'Addario4
1MediaPharma s.r.l., Via dei Vestini, 31, Chieti, Italy. e.piccolo@unich.it.
Background:
A previous report has shown that LGALS3BP (also known as 90K or Mac-2 BP) has antitumor activity in colorectal cancer (CRC) via suppression of Wnt signalling with a novel mechanism of ISGylation-dependent ubiquitination of β-catenin. The role of LGALS3BP in CRC prognosis was investigated.
Methods:
The role of LGALS3BP on CRC progression and clinical prognosis was analyzed by combining cell cultures, in vitro assays, and immunohistochemistry.
Results:
Silencing of LGALS3BP in HCT-116 human colon cancer cells resulted in enhanced β-catenin expression that was reversed by addition of human recombinant LGALS3BP. Moreover, intra-tumor delivery of LGALS3BP reduced tumor growth of xenografts originating from LGALS3BP-silenced HCT-116 cells. Finally, in a series of 196 CRC patients, LGALS3BP expression in tumor tissue associated with clinical outcome. Patients with high LGALS3BP expression had lower risk of relapse and a longer overall survival time than those with low LGALS3BP expression. Multivariate analyses confirmed LGALS3BP expression status as the only independent prognostic factor of survival.
Conclusions:
These results provide evidence that low expression of LGALS3BP participates in malignant progression of CRC and implicates poor prognosis, highlighting its augmentation as a potential therapeutic approach.
Insights
Low expression of LGALS3BP indicates poor prognosis in colorectal cancer (CRC). Increasing LGALS3BP levels may offer a new therapeutic strategy for CRC patients, improving survival and reducing relapse risk.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- LGALS3BP (90K/Mac-2 BP) exhibits antitumor activity in colorectal cancer (CRC) by suppressing Wnt signaling through ISGylation-dependent ubiquitination of β-catenin.
- The prognostic significance of LGALS3BP in CRC requires further investigation.
Purpose of the Study:
- To investigate the role of LGALS3BP in colorectal cancer progression.
- To determine the association between LGALS3BP expression and clinical prognosis in CRC patients.
Main Methods:
- Utilized cell cultures, in vitro assays, and immunohistochemistry to analyze LGALS3BP's role in CRC progression and prognosis.
- Investigated the effect of LGALS3BP silencing and recombinant protein addition on β-catenin expression in HCT-116 cells.
- Assessed tumor growth in xenograft models and analyzed LGALS3BP expression in 196 CRC patient tumor tissues.
Main Results:
- Silencing LGALS3BP increased β-catenin expression, which was reversible with recombinant LGALS3BP.
- Intra-tumor delivery of LGALS3BP reduced tumor growth in xenografts derived from LGALS3BP-silenced cells.
- High LGALS3BP expression in CRC patients correlated with a lower risk of relapse and longer overall survival, confirmed as an independent prognostic factor.
Conclusions:
- Low LGALS3BP expression is linked to malignant progression and poor prognosis in colorectal cancer.
- Augmenting LGALS3BP presents a potential therapeutic strategy for improving CRC patient outcomes.
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