Z Gastroenterol 2017; 55(08): e57-e299
DOI: 10.1055/s-0037-1604765
Kurzvorträge
Ösophagus und Magen
Karzinogenese und Therapieoptionen bei Ösophagus- und Magenkarzinom: Freitag, 15 September 2017, 11:40 – 13:00, Florenz/Forschungsforum 3
Georg Thieme Verlag KG Stuttgart · New York

S100A4 is related to an invasive phenotype and a poor outcome in patients with adenocarcinoma of the stomach and esophagus

C Treese
1   Charité – Universitätsmedizin Berlin, CBF, Department of Gastroenterology, Infectious Diseases and Rheumatology, Berlin, Deutschland
2   Experimental and Clinical Research Center, Charité University Medicine, Berlin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Deutschland
3   Berlin Institute of Health, Berlin, Deutschland
,
K Hartel
2   Experimental and Clinical Research Center, Charité University Medicine, Berlin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Deutschland
,
E Berg
4   Charité – Universitätsmedizin Berlin, Institute of Pathology, Berlin, Deutschland
,
M Hummel
4   Charité – Universitätsmedizin Berlin, Institute of Pathology, Berlin, Deutschland
,
M von Winterfeld
4   Charité – Universitätsmedizin Berlin, Institute of Pathology, Berlin, Deutschland
,
M Dahlmann
2   Experimental and Clinical Research Center, Charité University Medicine, Berlin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Deutschland
,
D Kobelt
2   Experimental and Clinical Research Center, Charité University Medicine, Berlin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Deutschland
,
B Siegmund
5   Charité – Universitätsmedizin Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, Berlin, Deutschland
,
S Daum
5   Charité – Universitätsmedizin Berlin, Department of Gastroenterology, Infectious Diseases and Rheumatology, Berlin, Deutschland
,
U Stein
2   Experimental and Clinical Research Center, Charité University Medicine, Berlin and Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Deutschland
6   German Cancer Consortium (DKTK), Heidelberg, Deutschland
› Author Affiliations
Further Information

Publication History

Publication Date:
02 August 2017 (online)

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Introduction:

Only 15% of patients with adenocarcinoma of the stomach and esophagus (ASE) survive longer than 5 years. Main reason for this is the development of metastasis. One of the key mechanisms of metastasis in these tumors is a deregulated Wnt-signaling. The oncogene S100A4 was identified as a Wnt-signaling target gene and is known to promote metastasis. In colorectal cancer, high S100A4 expression in tumors and its detection in patient blood correlate with reduced survival. In this project, we illuminate the role of S100A4 for metastases development and disease prognosis of ASE.

Methods:

Five gastric cancer cell lines were screened for S100A4 expression. Two cell lines with endogenous high S100A4 expression, FLO1 and NCI-N87, were selected for stable lentiviral S100A4 knockdown. Controls were generated by using a lentiviral vector with scrambled small hairpin RNA expression. Knockdown and control clones were used for functional phenotyping analyzing proliferation, migration and invasion. The prognostic value of S100A4 was evaluated by analyzing the S100A4 expression of tissue microarrays with samples of 277 patients with ASE.

Results:

The knockdown reduced the S100A4 mRNA expression in both cell lines effectively (FLO1 96.82% and NCI-N87 89.88%). Compared to the control, S100A4 knockdown showed a 57.17% lower migration (p = 0.02) and a 49.14% reduced invasion (p = 0.03) in FLO1 cells. In NCI-N87 cells, S100A4 knockdown showed a 15.71% lower migration (p = 0.16) but no reduced invasion (p = 0.95).

The analysis of S100A4 expression in tumor samples showed lower 5-year overall (17.1%) and disease-specific survival (19.3%) in S100A4 high expressing tumors than in S100A4 low expressing tumors (OS: 31.7%; p = 0.01, DSS: 37.4%; p = 0.02). Additionally, more patients developed metachronous metastases in the follow-up time of 126 months in the S100A4 high expressing (76.47%) than in the low expressing group (53.40%; p = 0.009).

Conclusion:

This study identifies S100A4 as a strong negative prognostic marker for patients with ASE. The strong correlation between S100A4 expression, metastases development and patient survival might open up opportunities to use S100A4 as a therapeutic target for intervention in this tumor entity and to improve the prognosis of these patients.