Arife Zeybek1, Necdet Öz2, Serdar Kalemci3, Kürşad Tosun4, Tuba Gökdoğan Edgünlü5, Mehmet Tuğhan Kızıltuğ6, Leyla Tekin7, Mehmet Emin Erdal6. 1. Department of Thoracic Surgery, Medical Faculty, School of Medicine, Mugla Sıtkı Kocman University, Mugla, Turkey. arifezeybek@mu.edu.tr. 2. Department of Thoracic Surgery, Private Antalya Med-Star Hospital, Antalya, Turkey. 3. Department of Chest Disease, Kocaeli Medikal Park Hospital, Kocaeli, Turkey. 4. School of Science, Siena College, New York, USA. 5. Department of Medical Biology, Medical Faculty, Mugla Sıtkı Kocman University, Mugla, Turkey. 6. Department of Medical Biology, Mersin University Medical Faculty, Mersin, Turkey. 7. Department of Medical Pathology, Medical Faculty, Mugla Sıtkı Kocman University, Mugla, Turkey.
Abstract
PURPOSE: We aimed to examine the expression levels of the genes encoding adenomatous polyposis coli (APC) 1, APC-2, Dickkopf related protein (DKK)-1, DKK-3, secreted frizzled-related protein (SFRP)-2, SFRP-4, and SFRP-5, which play roles in the Wnt signaling pathway, in lung adenocarcinoma and adjacent normal lung tissues and to evaluate their relationships with clinicopathologic factors. MATERIALS AND METHODS: The expression levels of genes in formalin-fixed paraffin-embedded samples of tumor tissue and adjacent intact lung tissue from 57 patients who underwent surgery for lung adenocarcinoma between 2011 and 2018 were determined by real-time PCR analysis. RESULTS: The expression levels of the DKK-1 in tumor tissue, especially in stage I-II tumor tissue, were significantly suppressed compared to those in normal tissue (p < 0.025). Whereas DKK-1 expression was suppressed in the tumor tissue of patients with early-stage lung adenocarcinoma, expression of the SFRP-5 in these patients was significantly higher in tumor tissue than in normal tissue (p < 0.039). CONCLUSION: In our study, opposing regulation was found between the SFRP-5 and DKK-1, which are known to be extracellular antagonists of the Wnt signaling pathway. The SFRP-5 was found to have an oncogenic role in adenocarcinoma development. Studies of the opposing regulation between these genes in early-stage lung adenocarcinoma may shed light on the mechanisms associated with the development of carcinogenesis. The relationships or interactions of these genes may serve as potential therapeutic targets.
PURPOSE: We aimed to examine the expression levels of the genes encoding adenomatous polyposis coli (APC) 1, APC-2, Dickkopf related protein (DKK)-1, DKK-3, secreted frizzled-related protein (SFRP)-2, SFRP-4, and SFRP-5, which play roles in the Wnt signaling pathway, in lung adenocarcinoma and adjacent normal lung tissues and to evaluate their relationships with clinicopathologic factors. MATERIALS AND METHODS: The expression levels of genes in formalin-fixed paraffin-embedded samples of tumor tissue and adjacent intact lung tissue from 57 patients who underwent surgery for lung adenocarcinoma between 2011 and 2018 were determined by real-time PCR analysis. RESULTS: The expression levels of the DKK-1 in tumor tissue, especially in stage I-II tumor tissue, were significantly suppressed compared to those in normal tissue (p < 0.025). Whereas DKK-1 expression was suppressed in the tumor tissue of patients with early-stage lung adenocarcinoma, expression of the SFRP-5 in these patients was significantly higher in tumor tissue than in normal tissue (p < 0.039). CONCLUSION: In our study, opposing regulation was found between the SFRP-5 and DKK-1, which are known to be extracellular antagonists of the Wnt signaling pathway. The SFRP-5 was found to have an oncogenic role in adenocarcinoma development. Studies of the opposing regulation between these genes in early-stage lung adenocarcinoma may shed light on the mechanisms associated with the development of carcinogenesis. The relationships or interactions of these genes may serve as potential therapeutic targets.
Authors: Karl Willert; Jeffrey D Brown; Esther Danenberg; Andrew W Duncan; Irving L Weissman; Tannishtha Reya; John R Yates; Roel Nusse Journal: Nature Date: 2003-04-27 Impact factor: 49.962