Evaluation of Impact of Tall Like Receptor 4 and Liposaccharide in Pathogenesis of Hepatic Cancer

Abstract

Functional TLR4 expression has been linked to HCC development. TLR4 may serve an important role in HCC development by promoting the malignant transformation of epithelial cells and tumor growth. The consequences might be dependent on the complex signaling networks triggered by TLR4 activation and the tumor microenvironment. The study included 90 consecutive subjects classified into 3 group their age from 40 to 70 years old. Group (I): HCC patients on top of chronic HCV infection. they were 45 patients 30 male and 15 females, their age ranged from 45 to 55 who were subdivided into 3 subgroups according to Barcelona clinic liver cancer (BCLC): Group (Ia): included 8 HCC patients in early stage. (stage A). Group (Ib): included 12 HCC patients in intermediate stage (stage B). Group (Ic): included 25 HCC patients in advanced stage. (stage C). Group (II): 30 Cirrhotic patients with chronic HCV, 21 male and 9 females, their age ranged from 50 to 60. This group was subdivided into 2 subgroups according to Child–Pugh score Group (IIa): included 8 Child–Pugh A. Group (IIb): included 22 Child–Pugh B and C. Group (III): controlled group included 15 normal subjects. 10 male and 5 females, their age ranged from 45 to 60. They were selected to match patients’ groups in demographic and socioeconomic standards. In our study where 15 persons are control showed lower level in TLR4 with mean 1.0±0.2, however 30 patients with HCV and other 45 patients with HCC showed higher level in TLR with mean 2.27±0.6 and 4.2±1.06 respectively. In our study there is statistically significant difference in serum TLR4 level between group (Ia) (2.25±0.5) and other subgroups which shows more increase in serum level of TLR4 in Group IB (3.2-1.06) than Group IA. Also shows more increase in serum level of TLR4 in Group IC (4.0±2.0) than Group IA and IB In our study HCC group showed higher level of LPS with mean 4.5±1.26 however lower in HCV group with mean 2.9-1.0 and least in control group with mean 1.1±0.4 In our study there is statistically significant difference in serum LPS level between group (IA) with mean 3.0±0.5 and other subgroups which shows more increase in serum level of LPS in Group IB with mean 4.4-1.0 than Group IA. Also shows more increase in serum level of LPS in Group IC with mean 4.0±1.76 than Group IA and IB In our study there is statistically significant difference in serum LPS level between group (IIB) and group (IIA) which shows more increase in serum level of TLR4 in Group IIB with mean 2.7±1.1 than Group IIA with mean 2.20±0.2 In our study there is statistically insignificant difference of the mean value ± SD of sex as regard to LPS and TLR expression (t = 1.2, p = 0.22). (t = 0.16, p = 0.87) respectively.In our study there is statistically significant positive correlation between ALT, AST, Platelets, alpha fetoprotein and LPS as regard to TLR4 expression in group II more in IIB,C than IA . but insignificant of the mean value ± SD of other parameters. In our study there is statistically significant difference of the mean value ± SD of ALT, AST, Platelets, alpha fetoprotein and TLR4 as regard to LPS expression in group I more in IB, C than IA. but insignificant of the mean value ± SD of other parameters.In our study there is statistically significant difference of the mean value ± SD of ALT, AST, Platelets and TLR4 as regard to LPS expression in group II more in IIB than IIA. but insignificant of the mean value ± SD of other parameters. Conclusion: TLR4 and LPS measurement should be carried for all patient with HCV Who are at risk for HCC with close monitoring. Conduct a study on a Gut microbiota as therapeutic targets for HCC.