The interaction of sphingosine1 phosphate, adiponectin, and sex Hormones with sex disparity among patients with hepatocellular carcinoma

Background: Previous studies showed contradictory data regarding sphingosine1-phosphate (S1P) levels in hepatocellular carcinoma (HCC) of HBV etiology and no data reported in HCV- related HCC. Role of S1P in liver fibrosis differs whether of HCV or HBV etiology. Experimental studies described interplay of S1P, adiponectin and sex hormones.
Aim: Studying sex disparity ad interplay of theses parameters in pathogenesis, diagnosis, clinic –morphological and staging of HCC.
Methods: Measurement of SIP, adiponectin and testosterone (T), estradiol (E) and sex hormone binding globulin (SHBG) among HCV–HCC group in comparing with HCV-related cirrhotic and healthy groups with their sex stratified subgroups.
Results: S1P was significantly higher in HCC patients with cut off value ≥ 113ng/l as screening test (sensitivity 95%, specificity 56%) for diagnosis of HCC diagnosis compared to sex -matched cirrhotic and healthy subjects. Compared to sex matched cirrhotic subgroups, male-HCC had significantly higher SHBG and lower adiponectin and estradiol while an opposite profile was observed in female-HCC. Female-HCC had significantly higher SIP and adiponectin than male-HCC. S1P level was positively correlated with adiponectin & testosterone and negatively correlated with E/T ratio in male and female HCC subgroups, adiponectin was negatively correlated with testosterone and SHBG and positively correlated with estradiol and E/T ratio among entire HCC group but reverse associations were observed in female-HCC. In females, large tumor size and higher T-class TNM staging were associated with higher adiponectin and testosterone and lower E/T ratio, and multiplicity was liked to higher estradiol. In males, an association between higher testosterone and higher T-class TNM staging was observed.
Conclusion: S1P is screening test for diagnosis of HCV-HCC which display sex disparity of association and interaction of S1P, adiponectin and, sex hormones in clinic-morphological features and staging