Elmira Gheytanchi1, Leili Saeednejad Zanjani1, Roya Ghods2,3, Maryam Abolhasani4, Marzieh Shahin4, Somayeh Vafaei5, Marzieh Naseri5, Fahimeh Fattahi5, Zahra Madjd6,7,8. 1. Oncopathology Research Center, Department of Molecular Medicine, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Tehran, 14496-14530, Iran. 2. Oncopathology Research Center, Department of Molecular Medicine, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Tehran, 14496-14530, Iran. rghods77@yahoo.com. 3. Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. rghods77@yahoo.com. 4. Department of Pathology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. 5. Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. 6. Oncopathology Research Center, Department of Molecular Medicine, Iran University of Medical Sciences (IUMS), Hemmat Street (Highway), Tehran, 14496-14530, Iran. zahra.madjd@yahoo.com. 7. Department of Molecular Medicine, Faculty of Advanced Technologies in Medicine, Iran University of Medical Sciences, Tehran, Iran. zahra.madjd@yahoo.com. 8. Department of Pathology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. zahra.madjd@yahoo.com.
Abstract
INTRODUCTION: Identification of genetic determinants such as exosomal content that drives progression and metastasis of colorectal cancer (CRC) has received considerable attention. The present study aims to identify a suitable biomarker in CRC tissues and exosomes based on bioinformatics data to evaluate its expression patterns in CRC tissues as well as its clinicopathological significance. MATERIALS AND METHODS: Protein-protein interaction (PPI) network and enrichment analysis were applied to identify up-regulated genes that contributed in CRC exosomes to select the marker. The expression patterns and clinical significance of selected exosomal marker were evaluated in tissue microarrays (TMAs) of 445 CRC tumors and 39 adjacent normal tissues using immunohistochemistry method. RESULTS: Based on bioinformatics data, TSG101 gene was prominent amongst the tumor tissues and exosomes. Expression of TSG101 was significantly up-regulated in tumor cells compared to adjacent normal tissues (p-value = 0.04). Moreover, higher expressions of TSG101 (cytoplasmic and nuclear) were significantly associated with tumor differentiation (p-value = 0.042) and distant metastasis (p-value = 0.027). A significant association was found in the cytoplasmic expression of TSG101 between well and moderate tumor differentiation (p-value = 0.005) as well as moderate and poor differentiation (p-value = 0.050). CONCLUSION: These findings indicate that the exploration of crosstalk between exosome content and CRC may be valuable for the development of novel exosomal biomarkers. Increased expression of TSG101, as a promising exosome marker, is more associated with more aggressive tumor behaviors, metastasis, and progression of CRC, which paves the way for therapeutic strategies and CRC management. However, further investigations are warranted to clarify the molecular mechanisms of TSG101 in CRC.
INTRODUCTION: Identification of genetic determinants such as exosomal content that drives progression and metastasis of colorectal cancer (CRC) has received considerable attention. The present study aims to identify a suitable biomarker in CRC tissues and exosomes based on bioinformatics data to evaluate its expression patterns in CRC tissues as well as its clinicopathological significance. MATERIALS AND METHODS: Protein-protein interaction (PPI) network and enrichment analysis were applied to identify up-regulated genes that contributed in CRC exosomes to select the marker. The expression patterns and clinical significance of selected exosomal marker were evaluated in tissue microarrays (TMAs) of 445 CRC tumors and 39 adjacent normal tissues using immunohistochemistry method. RESULTS: Based on bioinformatics data, TSG101 gene was prominent amongst the tumor tissues and exosomes. Expression of TSG101 was significantly up-regulated in tumor cells compared to adjacent normal tissues (p-value = 0.04). Moreover, higher expressions of TSG101 (cytoplasmic and nuclear) were significantly associated with tumor differentiation (p-value = 0.042) and distant metastasis (p-value = 0.027). A significant association was found in the cytoplasmic expression of TSG101 between well and moderate tumor differentiation (p-value = 0.005) as well as moderate and poor differentiation (p-value = 0.050). CONCLUSION: These findings indicate that the exploration of crosstalk between exosome content and CRC may be valuable for the development of novel exosomal biomarkers. Increased expression of TSG101, as a promising exosome marker, is more associated with more aggressive tumor behaviors, metastasis, and progression of CRC, which paves the way for therapeutic strategies and CRC management. However, further investigations are warranted to clarify the molecular mechanisms of TSG101 in CRC.
Authors: Tanya Barrett; Stephen E Wilhite; Pierre Ledoux; Carlos Evangelista; Irene F Kim; Maxim Tomashevsky; Kimberly A Marshall; Katherine H Phillippy; Patti M Sherman; Michelle Holko; Andrey Yefanov; Hyeseung Lee; Naigong Zhang; Cynthia L Robertson; Nadezhda Serova; Sean Davis; Alexandra Soboleva Journal: Nucleic Acids Res Date: 2012-11-27 Impact factor: 16.971
Authors: Justyna K Broniarczyk; Alicja Warowicka; Anna Kwaśniewska; Maria Wohuń-Cholewa; Wojciech Kwaśniewski; Anna Goździcka-Józefiak Journal: Oncol Lett Date: 2014-03-11 Impact factor: 2.967