The impact of CD8 and CTLA-4 expression on histopathological character and survival in mesothelioma
	    		
		   		
		   			
		   		
	    	
    	 
    	10.3760/cma.j.cn121094-20200831-00506
   		
        
        	
        		- VernacularTitle:CD8和CTLA-4表达程度对间皮瘤组织病理学特征和生存的影响分析
 
        	
        	
        	
        		- Author:
	        		
		        		
		        		
			        		Min YU
			        		
			        		
			        		
			        			1
			        			
			        		
			        		
			        		
			        		
			        		;
		        		
		        		
		        		
			        		Man YU
			        		
			        		;
		        		
		        		
		        		
			        		Shibo YING
			        		
			        		;
		        		
		        		
		        		
			        		Xiuyuan YUAN
			        		
			        		;
		        		
		        		
		        		
			        		Zhaoqiang JIANG
			        		
			        		;
		        		
		        		
		        		
			        		Jianlin LOU
			        		
			        		;
		        		
		        		
		        		
			        		Lijin ZHU
			        		
			        		;
		        		
		        		
		        		
			        		Xing ZHANG
			        		
			        		
		        		
		        		
		        		
		        		
		        			
			        		
			        		Author Information
			        		
		        		
		        		
			        		
			        		
			        			1. 310013 杭州医学院(浙江省医学科学院)公共卫生学院
			        		
		        		
	        		
        		 
        	
        	
        	
        	
        		- Keywords:
        			
	        			
	        				
	        				
			        		
				        		Mesothelioma;
			        		
			        		
			        		
				        		Cytotoxic T lymphocyte-associated antigen-4;
			        		
			        		
			        		
				        		5-methylcytosine;
			        		
			        		
			        		
				        		Ki-67 antigen
			        		
			        		
	        			
        			
        		
 
        	
            
            
            	- From:
	            		
	            			Chinese Journal of Industrial Hygiene and Occupational Diseases
	            		
	            		 2021;39(2):85-90
	            	
            	
 
            
            
            	- CountryChina
 
            
            
            	- Language:Chinese
 
            
            
            	- 
		        	Abstract:
			       	
			       		
				        
				        	Objective:To investigate the survival and death risk factors of mesothelioma cases stratified by the expression levels of CD8 and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) , providing new clue to evaluate disease progression and clinical outcome.Methods:This was a retrospective case report, which included 47 clinically and pathologically confirmed mesothelioma cases on November 2016. Their clinical and pathological information, asbestos exposure history and survival data were collected. Infiltrated lymphocyte, 5-methylcytosine (5-mC) , CTLA-4, CD8 and Ki-67 antigen were detected using hematoxylin-eosin staining and immunohistochemistry. Survival time and death risk factors of mesothelioma patients with different CD8 and CTLA-4 protein expression characteristics were analyzed. And analyze the influence of Ki-67 expression on the survival of patients with different CD8 and CTLA-4 protein and gene expression characteristics.Results:Among the 47 cases, 63.8% (30/47) had low/medium level of infiltrated lymphocyte. The immunohistochemistry scores of CTLA-4, CD8, 5-mC and Ki-67 were 92.97 (54.95, 120.65) , 72.41 (36.62, 89.82) , 11.09 (3.40, 52.89) and 5.88 (2.41, 11.48) , respectively. Patients with CD8 high CTLA-4 high had higher 5-mC level than those with CD8 high CTLA-4 low ( P<0.01) . The median survival time of 27 cases was 0.83±0.29 year. The median survival times of those with CD8 high CTLA-4 high and CD8 high CTLA-4 low were 0.58±0.51 year and 0.83±0.30 year, respectively ( P=0.521) . The immunohistochemistry score of Ki-67 ≥5.88 was an independent death risk factor for patients with CD8 high CTLA-4 low ( HR=8.40, P=0.01) . Under different CD8 and CTLA-4 protein expression characteristics, in the patients with CD8 high CTLA-4 low, the median survival times of those with high and low Ki-67 expression were 0.57±0.11 years and 2.31±0.46 years, respectively ( P<0.01) . Under different CD8 and CTLA-4 mRNA expression characteristics, in the patients with CD8 high CTLA-4 low, the median survival times of those with high and low Ki-67 mRNA expression were 1.20±0.36 years and 3.38±0.43 years, respectively ( P=0.018) . Conclusion:Mesothelioma case with high CD8 but low CTLA-4 content might coexist DNA hypomethylation. In the presence of high Ki-67 expression, their survival time appears to be shortened with increased death risk.