Relationship of CRIM1 and epithelial-mesenchymal transition in hepatocellular carcinoma

Abstract

Objective To study the expression and the clinical significance of cysteine rich transmembrane BMP regulator 1(CRIM1) in hepatocellular carcinoma(HCC) and discuss the association between CRIM1 and epithelial-mesenchymal transition(EMT). Methods The cases were came from the Subei People′s Hospital Affilated Hospital of Yangzhou University from January 2013 to December 2017. CRIM1 and EMT related proteins (E-cadherin, Vimentin) in parts of HCC tissues and their paired peritumoural tissues were tested by Western blotting. The gray value was test by t test. The observation indicators: (1) expression of CRIM1 protein and EMT-related protein (E-cadherin, Vimentin) in liver cancer tissues and paracancerous tissues. (2) The relationship between CRIM1 protein expression and clinicopathological factors in patients with liver cancer. The expression of CRIM1 in HCC tissues and adjacent tissues was detected by immunohistochemistry(IHC), which was divided into high expression group and low expression group according to the histochemical score, and the relation between the expression of CRIM1 and the clinicopathological factors of the patients was analyzed by chi-square test and Spearman correlation analysis. Finally, the relation between CRIM1 and overall survival of HCC patients was analyzed by Kaplan Meier Plotter database. Results The expression of CRIM1 in tumor and matched paratumor specimens were 0.15 ± 0.03, 0.8 ± 0.04, and E-cadherinin tumor and matched paratumor specimenswere 0.20±0.05, 0.56±0.06, their expression in paracancerous tissues was higher than HCC tissues(t=14.21, 4.69, P<0.05), while the expression of Vimentin in tumor and matched paratumor specimens were 0.74 ± 0.08, 0.45 ± 0.06, the expression in tumor tissues were significantly higher than adjacent tissues(t=2.87, P<0.05). The expression of CRIM1 in HCC tissues was further verified by immunohistochemistry, which shows that CRIM1 was overexpressed in paracancerous tissues. In 114 patients, 46 cases of CRIM1 protein were highly expressed in liver cancer tissues, and 68 cases of CRIM1 protein were low expressed. The expression of CRIM1 obviously related with the level of α-fetoprotein (AFP), tumor size and symptom(r=-0.43, -0.34, -0.24, χ2=9.381, 5.248, 8.117, P<0.05). However, other clinicopathological features were not correlated with CRIM1 expression, including age, tumour differentiation, tumor number. Finally, the overall survival was different between CRIM1 high expression and low expression according to the Kaplan Meier Plotter database. Conclusions The expression of CRIM1 is negatively correlated with the EMT process in HCC. CRIM1 might be a potential molecular marker for prognosis. Key words: Carcinoma, hepatocellular; Immunohistochemistry; Cysteine rich transmembrane BMP regulator 1; Epithelial-mesenchymal transition