Abstract 896: A systematic search in tumor interstitial fluid identifying a tumor-specific interleukin-hypoxia-glycolysis-DNA repair pathway and a novel serum marker RBB3 for human hepatoma

Abstract

Abstract The long-term outcome of patients with hepatocellular carcinoma (HCC) remains undesirable, primarily due to late diagnosis and high recurrence. We aimed to discover new markers for early detection and prediction of recurrence. We initiated our search by comparing the proteomes of the interstitial fluid of HCC (TIF) and nonHCC liver tissues by using proteomic approaches. About 150 proteins were found to be dysregulated in TIF. Gene ontology analysis and biofunction reconstruction revealed the involvement of “interleukin-hypoxia-glycolysis-DNA repair pathway” in HCC. To search for novel serum markers, we identified secreted RBB3 (sRBB3) significantly increased their amount in TIF. Further studies disclosed that the serum sRBB3 level was significantly higher in HCC (113 cases) than in cirrhosis (47 cases)(p < 0.001) and chronic hepatitis (64 cases)(p < 0.001). The accuracy of serum sRBB3 in detection of HCC was further validated in 2 independent sets (92 cases in each set) of patients by using receiver operating characteristic (ROC) curve. A sensitivity of 89.3% and a specificity of 99.7% were obtained. Moreover, serum srbb3 had a better performance than serum alpha-fetoprotein (AFP) in discrimination of early HCC from chronic hepatitis [areas under the ROC curves (AUC) for srbb3 vs. AFP = 0.931 vs. 0.810] and from cirrhosis (AUCs: serbb3 vs. AFP = 0.709 vs. 0.627). The serum sRBB3 level was strongly associated with portal vein invasion and extrahepatic metastasis of HCC (p = 0.017). The performance of the combination of serum srbb3 and AFP was similar to that of srbb3 but better than that of AFP in discrimination of HCC from non-HCC. Conclusion: Interstitial fluid of tumor tissues is a good source in the search for novel tumor markers. An immune-mediated tumor microenvironment plays roles in genome damage and possibly tumorigenesis of HCC. Serum srbb3 is a better HCC marker than AFP, particularly for detection of early HCC and for portal vein invasion and extrahepatic metastatsis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 896. doi:10.1158/1538-7445.AM2011-896