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

被引：10

作者：

Klupp, Fee ^{[1
]}

Kahlert, Christoph ^{[2
]}

Franz, Clemens ^{[1
]}

Halama, Niels ^{[3
]}

Schleussner, Nikolai ^{[1
]}

Wirsik, Naita M. ^{[4
]}

Warth, Arne ^{[5
]}

Schmidt, Thomas ^{[1
,4
]}

Ulrich, Alexis B. ^{[1
,6
]}

机构：

[1] Heidelberg Univ, Dept Gen Visceral & Transplantat Surg, Neuenheimer Feld 420, D-69120 Heidelberg, Germany

[2] Univ Dresden, Dept Visceral Thorac & Vasc Surg, Fetscherstr 74, D-01307 Dresden, Germany

[3] Heidelberg Univ, Natl Ctr Tumor Dis Med Oncol & Internal Med 6, Tissue Imaging & Anal Ctr, Bioquant, Neuenheimer Feld 267, D-69120 Heidelberg, Germany

[4] Univ Hosp Cologne, Dept Gen Visceral & Tumor Surg, Kerpener Str 62, D-50937 Cologne, Germany

[5] Heidelberg Univ, Inst Pathol, Neuenheimer Feld 224, D-69120 Heidelberg, Germany

[6] Lukas Hosp Neuss, Dept Gen & Visceral Surg, Preuenstr 84, D-41464 Neuss, Germany

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2021年 / 22卷 / 12期

关键词：

colorectal cancer; adenomas; granulin; GRN; survival; EPITHELIN PRECURSOR; GROWTH-FACTOR; HEPATOCELLULAR-CARCINOMA; PROGRANULIN; PROMOTES; CELLS; EXPRESSION; PROEPITHELIN; INFLAMMATION; CROSSROADS;

D O I：

10.3390/ijms22126436

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页数：11

共 42 条

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