Abstract Background: HCC is a complex disease with tumor growth replacing adjacent liver. Our initial hypothesis was that tumor traits and loss of liver function are independent processes. We examined this, seeking evidence of coherent discrete structure with respect to survival. Methods: NPS was used to analyze 970 patients with biopsy-proven, non-surgical HCC, all followed prospectively until death. We assumed stochasticity with respect to timing of diagnosis and ambiguity of each variable with respect to survival and used a combination of k-partite graph-based analysis with statistical processing of pairwise dependencies of clinical data ordered by survival, each characterized by the mean of clinical parameters of the 100 patients with the closest survival, for 678 survivals. Results: NPS clearly identified heterogeneity, with 3 distinctive phenotypes based on coherence of multiple variables. Each had different survival ranges with trends of collinear relationships between bilirubin, AFP, alkaline phosphatase, SGOT and GGTP. In patients >70 years, the larger the tumor the higher the biochemical values, with the trends decreasing with longer survival. Above 80 years, bilirubin and AFP were normal, with long survival, 330-1250 days. There were 2 groups of younger patients (<55 years). One, with 30-45 days survival, had a similar profile to the older group. In the other, with 90-330 days survival, the profile was for multiple small tumors to trend with biochemical values. A striking finding was the close correlation in trends for AFP against bilirubin, alkaline phosphatase, GGTP or SGOT values, suggesting that liver damage parameters and tumor parameters were not independent factors, but might be inter-twined, especially in older patients. Conclusions: This NPS analysis does not support the hypothesis that tumor growth and cirrhotic damage are independent, but are intertwined processes. Furthermore, we have evidence based on coherence between variables that the growth rates for unifocal tumors of equivalent size are faster in the young than in the elderly. NPS provides useful insights to design future genomic studies to compare different phenotypes and understand the different pathophysiological processes involved. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2010.