Tiemo S Gerber1, Fabian Bartsch2, Daniel C Wagner1, Mario Schindeldecker1,3, Lisa-Katharina Heuft2, Wilfried Roth1, Hauke Lang2, Beate K Straub1. 1. Institute of Pathology, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany. 2. Department of General, Visceral and Transplant Surgery, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany. 3. Tissue Biobank, University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany.
Abstract
BACKGROUND: Syndecan-1 (CD138; SDC1) is a heparan sulfate proteoglycan that has been attributed a key role in cancer progression in ductal adenocarcinoma of the pancreas. We therefore aimed to investigate the role of syndecan-1 in cholangiocarcinoma. METHODS: We analyzed syndecan-1 expression in a large, clinicopathologically well-characterized collective of 154 intrahepatic cholangiocarcinoma, 221 extrahepatic cholangiocarcinomas, and 95 gallbladder carcinomas as well as respective normal tissues and precursor lesions by immunohistochemistry with digital image analysis and correlated with recurrence-free survival and prognostic markers. Furthermore, we conducted an analysis of cancer genes in the cholangiocarcinoma cohort of The Cancer Genome Atlas (TCGA). RESULTS: During cholangiocarcinogenesis, syndecan-1-expression decreased when compared to normal bile ducts and biliary intraepithelial neoplasia; however, syndecan-1 levels were found to be elevated in lymph node metastases. In the TCGA cohort, high mRNA SDC1 levels were associated with poor prognosis in intrahepatic cholangiocarcinoma. However, in our large cohort, the immunohistochemical syndecan-1 expression did not significantly correlate with recurrence-free survival. CONCLUSIONS: Syndecan-1 was found to be downregulated during cholangiocarcinogenesis, yet we could not show significant effects on prognosis on protein level. Further analyses are needed to further depict its specific role.
BACKGROUND:Syndecan-1 (CD138; SDC1) is a heparan sulfate proteoglycan that has been attributed a key role in cancer progression in ductal adenocarcinoma of the pancreas. We therefore aimed to investigate the role of syndecan-1 in cholangiocarcinoma. METHODS: We analyzed syndecan-1 expression in a large, clinicopathologically well-characterized collective of 154 intrahepatic cholangiocarcinoma, 221 extrahepatic cholangiocarcinomas, and 95 gallbladder carcinomas as well as respective normal tissues and precursor lesions by immunohistochemistry with digital image analysis and correlated with recurrence-free survival and prognostic markers. Furthermore, we conducted an analysis of cancer genes in the cholangiocarcinoma cohort of The Cancer Genome Atlas (TCGA). RESULTS: During cholangiocarcinogenesis, syndecan-1-expression decreased when compared to normal bile ducts and biliary intraepithelial neoplasia; however, syndecan-1 levels were found to be elevated in lymph node metastases. In the TCGA cohort, high mRNA SDC1 levels were associated with poor prognosis in intrahepatic cholangiocarcinoma. However, in our large cohort, the immunohistochemical syndecan-1 expression did not significantly correlate with recurrence-free survival. CONCLUSIONS:Syndecan-1 was found to be downregulated during cholangiocarcinogenesis, yet we could not show significant effects on prognosis on protein level. Further analyses are needed to further depict its specific role.
Authors: Tiemo S Gerber; Lukas Müller; Fabian Bartsch; Lisa-Katharina Gröger; Mario Schindeldecker; Dirk A Ridder; Benjamin Goeppert; Markus Möhler; Christoph Dueber; Hauke Lang; Wilfried Roth; Roman Kloeckner; Beate K Straub Journal: Cancers (Basel) Date: 2022-06-28 Impact factor: 6.575
Authors: Tiemo S Gerber; Benjamin Goeppert; Anne Hausen; Hagen R Witzel; Fabian Bartsch; Mario Schindeldecker; Lisa-Katharina Gröger; Dirk A Ridder; Oscar Cahyadi; Irene Esposito; Matthias M Gaida; Peter Schirmacher; Peter R Galle; Hauke Lang; Wilfried Roth; Beate K Straub Journal: Cancers (Basel) Date: 2022-06-23 Impact factor: 6.575
Authors: Tiemo Sven Gerber; Dirk Andreas Ridder; Mario Schindeldecker; Arndt Weinmann; Diane Duret; Kai Breuhahn; Peter R Galle; Peter Schirmacher; Wilfried Roth; Hauke Lang; Beate Katharina Straub Journal: Cells Date: 2022-08-12 Impact factor: 7.666