Granulin: an invasive and survival-determining marker in colorectal cancer patients

Background: Granulin is a secreted, glycosylated peptide—originated by cleavage from a precursor protein—which is involved in cell growth, tumor invasion and angiogenesis. However, the specific prognostic impact of granulin in human colorectal cancer has only been studied to a limited extent. Thus,...

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Main Authors: Klupp, Fee (Author) , Kahlert, Christoph (Author) , Franz, Clemens (Author) , Halama, Niels (Author) , Schleußner, Nikolai (Author) , Wirsik, Naita Maren (Author) , Warth, Arne (Author) , Schmidt, Thomas (Author) , Ulrich, Alexis (Author)
Format: Article (Journal)
Language:English
Published: 16 June 2021
In: International journal of molecular sciences
Year: 2021, Volume: 22, Issue: 12, Pages: 1-11
ISSN:1422-0067
DOI:10.3390/ijms22126436
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/ijms22126436
Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/1422-0067/22/12/6436
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Author Notes:Fee Klupp, Christoph Kahlert, Clemens Franz, Niels Halama, Nikolai Schleussner, Naita M. Wirsik, Arne Warth, Thomas Schmidt and Alexis B. Ulrich

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520 |a Background: Granulin is a secreted, glycosylated peptide—originated by cleavage from a precursor protein—which is involved in cell growth, tumor invasion and angiogenesis. However, the specific prognostic impact of granulin in human colorectal cancer has only been studied to a limited extent. Thus, we wanted to assess the expression of granulin in colorectal cancer patients to evaluate its potential as a prognostic biomarker. Methods: Expressional differences of granulin in colorectal carcinoma tissue (n = 94) and corresponding healthy colon mucosa were assessed using qRT-PCR. Immunohistochemistry was performed in colorectal cancer specimens (n = 97), corresponding healthy mucosa (n = 47) and colorectal adenomas (n = 19). Subsequently, the results were correlated with histopathological and clinical patients’ data. HCT-116 cells were transfected with siRNA for invasion and migration assays. Results: Immunohistochemistry and qRT-PCR revealed tumoral over expression of granulin in colorectal cancer specimens compared to corresponding healthy colon mucosa and adenomas. Tumoral overexpression of granulin was associated with a significantly impaired overall survival. Moreover, downregulation of granulin by siRNA significantly diminished the invasive capacities of HCT-116 cells in vitro. Conclusion: Expression of granulin differs in colorectal cancer tissue, adenomas and healthy colon mucosa. Furthermore, granulin features invasive and migrative capabilities and overexpression of granulin correlates with a dismal prognosis. This reveals its potential as a prognostic biomarker and granulin could be a worthwhile molecular target for individualized anticancer therapy. 
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