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. 2021 Jun 16;22(12):6436.
doi: 10.3390/ijms22126436.

Granulin: An Invasive and Survival-Determining Marker in Colorectal Cancer Patients

Fee Klupp  1 , Christoph Kahlert  2 , Clemens Franz  1 , Niels Halama  3 , Nikolai Schleussner  1 , Naita M Wirsik  4 , Arne Warth  5 , Thomas Schmidt  1   4 , Alexis B Ulrich  1   6
Affiliations

Granulin: An Invasive and Survival-Determining Marker in Colorectal Cancer Patients

Fee Klupp et al. Int J Mol Sci. .

Abstract

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.

Keywords: GRN; adenomas; colorectal cancer; granulin; survival.

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Conflict of interest statement

The authors declare that they have no conflict of interest.

Figures

Figure 1
Figure 1
Expression level of granulin. Granulin in tumoral tissue of colorectal cancer specimen and corresponding healthy colon mucosa normalized to 18s rRNA (n = 94), (p = 0.059). Bar represents mean + SEM.
Figure 2
Figure 2
Immunohistochemistry revealing spatial localization of granulin protein. Granulin was strongly expressed in the tumor cells (A), particularly in the cytoplasm, and showed a descending expression in colorectal adenomas (B), whereas there was almost no expression of granulin in healthy mucosa cells (C).
Figure 3
Figure 3
Invasion (A) and migration (B) assays. Granulin siRNA-transfected HCT-116 cells were less migratory (p = 0.074) and significantly less invasive (* p = 0.013). Bars represent mean + SEM.
Figure 4
Figure 4
Correlation of granulin expression and overall survival (n = 89). Overall survival was significantly impaired in patients with high tumoral granulin expression (p = 0.047).
See this image and copyright information in PMC

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