Interplay of Sphingosine1 phosphate, Adiponectin and Sex Hormones with Gender disparity among patients with Hepatocellular Carcinoma

Abstract Backgroundcirculating sphingosine 1-phosphate (S1P) showed oncogenic roles in various cancers. It showed conflict data in Hepatitis B virus- hepatocellular carcinoma (HCC). Adiponectin and sex hormones were contributing factors for gender disparity in HCC. Up to date, no clinical study among HCC patients addresses interplay of S1P, adiponectin and sex hormones that was described in experimental studies. The current study aimed to evaluate circulating SIP, adiponectin and sex hormones among sex stratified HCC subgroups and to assess gender disparity of theses parameters regarding HCC development and diagnosis, their interplay and association with clinic -morphological and staging of HCC.MethodWe measures serum S1P, adiponectin, testosterone (T), estradiol (E) and sex hormone binding globulin (SHBG), calculated free and bioavailable T and E/T ratio among HCV – HCC group in comparing with comparable HCV- cirrhotic and healthy groups with their sex stratified male and female subgroupsResultsAmong all, male and female HCC patients, S1P was significant higher than corresponding cirrhotic and healthy subjects with cut off value ≥ 113ng/l as screening test (sensitivity 95%, specificity 56%) for HCC diagnosis. Compared to sex respective cirrhotic subgroups, male-HCC had significant higher SHBG and lower adiponectin and estradiol while opposite profile was observed among female-HCC. Female-HCC had significant higher SIP and adiponectin than male-HCC. Although S1P was positively correlated with adiponectin, testosterone and negatively with E/T ratio among male and female HCC, adiponectin was correlated negatively with testosterone and SHBG and positively with estradiol and E/T ratio among entire HCC group but reverse associations were observed in female (not- male) subgroup. Associations of large tumor size and higher T-class TNM staging with higher adiponectin and testosterone and lower E/T ratio and link of multiplicity with higher estradiol in females while association of higher testosterone among higher T-class TNM staging male were observed. Portal vein thrombosis was related to lower SHBG and higher testosterone in male and female respectively.ConclusionWe suggested S1P as screening test for diagnosis of HCC among HCV-cirrhotic and healthy subjects. There was gender disparity as regard association and interaction of S1P, adiponectin and sex hormone with respect of HCC development and its clinic-morphological features and staging.