Fee Klupp1, Johannes Diers1, Christoph Kahlert1, Lena Neumann1, Niels Halama2, Clemens Franz1, Thomas Schmidt1, Felix Lasitschka3,4, Arne Warth3, Juergen Weitz5, Moritz Koch5, Martin Schneider6, Alexis Ulrich1. 1. Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. 2. National Center for Tumor Diseases, Medical Oncology, and Internal Medicine VI, Tissue Imaging and Analysis Center, Bioquant, University of Heidelberg, Heidelberg, Germany. 3. Institute of Pathology, University of Heidelberg, Heidelberg, Germany. 4. Tissue Bank of the National Center for Tumor Diseases (NCT), Heidelberg, Germany. 5. Department of Visceral, Thoracic, and Vascular Surgery, University of Dresden, Dresden, Germany. 6. Department of General, Visceral, and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany. m.schneider@uni-heidelberg.de.
Abstract
BACKGROUND: Signal transducer and activator of transcription proteins (STATs) are crucial regulators of cell growth and differentiation; however, their specific prognostic impact in human colon cancer has only been studied to limited extent. We aimed to assess the prognostic significance of specific STAT expression patterns in colon carcinoma. METHODS: Protein expression patterns of activated STAT1, STAT3, STAT4, and STAT5 in human colon carcinoma tissue and corresponding healthy mucosa (n = 104) were assessed using multiplex bead-based immunoassay technologies. Expression patterns were correlated with clinical and survival data. Immunohistochemistry was performed to assess spatial expression of STAT3 and STAT5. RESULTS: STAT3 was underexpressed whereas STAT4 and STAT5 were overexpressed in colon carcinoma tissue. Primary tumors from patients with distant metastases (M1) displayed significantly increased expression of STAT1 and STAT3 but decreased expression of STAT4 and STAT5. Increased tumor expression of STAT1 or STAT3 was associated with impaired patient survival, whereas increased expression of STAT4 or STAT5 correlated with improved survival. Multivariate analysis identified an increased STAT3/STAT5 expressional ratio as an adverse prognostic marker in colon cancer patients. CONCLUSIONS: The tumor progression-associated transcription factors STAT3, STAT4, and STAT5 are differently expressed in colon carcinoma tissue and colon mucosa. Moreover, the STAT3/STAT5 expression ratio is an independent prognostic marker in colon cancer patients.
BACKGROUND: Signal transducer and activator of transcription proteins (STATs) are crucial regulators of cell growth and differentiation; however, their specific prognostic impact in humancolon cancer has only been studied to limited extent. We aimed to assess the prognostic significance of specific STAT expression patterns in colon carcinoma. METHODS: Protein expression patterns of activated STAT1, STAT3, STAT4, and STAT5 in humancolon carcinoma tissue and corresponding healthy mucosa (n = 104) were assessed using multiplex bead-based immunoassay technologies. Expression patterns were correlated with clinical and survival data. Immunohistochemistry was performed to assess spatial expression of STAT3 and STAT5. RESULTS:STAT3 was underexpressed whereas STAT4 and STAT5 were overexpressed in colon carcinoma tissue. Primary tumors from patients with distant metastases (M1) displayed significantly increased expression of STAT1 and STAT3 but decreased expression of STAT4 and STAT5. Increased tumor expression of STAT1 or STAT3 was associated with impaired patient survival, whereas increased expression of STAT4 or STAT5 correlated with improved survival. Multivariate analysis identified an increased STAT3/STAT5 expressional ratio as an adverse prognostic marker in colon cancerpatients. CONCLUSIONS: The tumor progression-associated transcription factors STAT3, STAT4, and STAT5 are differently expressed in colon carcinoma tissue and colon mucosa. Moreover, the STAT3/STAT5 expression ratio is an independent prognostic marker in colon cancerpatients.
Authors: Satoshi Matsusaka; Diana L Hanna; Shu Cao; Wu Zhang; Dongyun Yang; Yan Ning; Yu Sunakawa; Satoshi Okazaki; Martin D Berger; Yuji Miyamato; Anish Parekh; Sebastian Stintzing; Fotios Loupakis; Heinz-Josef Lenz Journal: Clin Cancer Res Date: 2016-02-02 Impact factor: 12.531
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