| 4 | Insulin receptor substrate 1 may play divergent roles in human colorectal cancer development and progression显示文摘BACKGROUND Despite effective prevention and screening methods,the incidence and mortality rates associated with colorectal cancer(CRC)are still high.Insulin receptor substrate 1(IRS-1),a signaling molecule involved in cell proliferation,survival and metabolic responses has been implicated in carcinogenic processes in various cellular and animal models.However,the role of IRS-1 in CRC biology and its value as a clinical CRC biomarker has not been well defined.AIM To evaluate if and how IRS-1 expression and its associations with the apoptotic and proliferation tumor markers,Bax,Bcl-xL and Ki-67 are related to clinicopathological features in human CRC.METHODS The expression of IRS-1,Bax,Bcl-xL and Ki-67 proteins was assessed in tissue samples obtained from 127 patients with primary CRC using immunohistochemical methods.The assays were performed using specific antibodies against IRS-1,Bax,Bcl-xL,Ki-67.The associations between the expression of IRS-1,Bax,Bcl-xL,Ki-67 were analyzed in relation to clinicopathological parameters,i.e.,patient age,sex,primary localization of tumor,histopathological type,grading,staging and lymph node spread.Correlations between variables were examined by Spearman rank correlation test and Fisher exact test with a level of significance at P<0.05.RESULTS Immunohistochemical analysis of 127 CRC tissue samples revealed weak cytoplasmatic staining for IRS-1 in 66 CRC sections and strong cytoplasmatic staining in 61 cases.IRS-1 expression at any level in primary CRC was associated with tumor grade(69%in moderately differentiated tumors,G2 vs 31%in poorly differentiated tumors,G3)and with histological type(81.9%in adenocarcinoma vs 18.1%in adenocarcinoma with mucosal component cases).Strong IRS-1 positivity was observed more frequently in adenocarcinoma cases(95.1%)and in moderately differentiated tumors(85.2%).We also found statistically significant correlations between expression of IRS-1 and both Bax and Bcl-xL in all CRC cases examined.The relationships between studied proteins were related to clinicopathological parameters of CRC.No significant correlation between the expression of IRS-1 and proliferation marker Ki-67,excluding early stage tumors,where the correlation was positive and on a high level(P=0.043,r=0.723).CONCLUSION This study suggests that IRS-1 is co-expressed with both pro-and antiapoptotic markers and all these proteins are more prevalent in more differentiated CRC than in poorly differentiated CRC. | Karolina Lomperta Katarzyna Jakubowska Malgorzata Grudzinska Luiza Kanczuga-Koda Andrzej Wincewicz Eva Surmacz Stanislaw Sulkowski Mariusz Koda | 2020 | World Journal of Gastroenterology2020，26，28： | 0 |
您所在的机构暂未开通此部分的功能，请联系管理员