Abstract
BackgroundThe prognosis of hepatocellular carcinoma (HCC) varies following surgical resection and the large variation remains largely unexplained. Studies have revealed the ability of clinicopathologic parameters and gene expression to predict HCC prognosis. However, there has been little systematic effort to compare the performance of these two types of predictors or combine them in a comprehensive model.MethodsTumor and adjacent non-tumor liver tissues were collected from 272 ethnic Chinese HCC patients who received curative surgery. We combined clinicopathologic parameters and gene expression data (from both tissue types) in predicting HCC prognosis. Cross-validation and independent studies were employed to assess prediction.ResultsHCC prognosis was significantly associated with six clinicopathologic parameters, which can partition the patients into good- and poor-prognosis groups. Within each group, gene expression data further divide patients into distinct prognostic subgroups. Our predictive genes significantly overlap with previously published gene sets predictive of prognosis. Moreover, the predictive genes were enriched for genes that underwent normal-to-tumor gene network transformation. Previously documented liver eSNPs underlying the HCC predictive gene signatures were enriched for SNPs that associated with HCC prognosis, providing support that these genes are involved in key processes of tumorigenesis.ConclusionWhen applied individually, clinicopathologic parameters and gene expression offered similar predictive power for HCC prognosis. In contrast, a combination of the two types of data dramatically improved the power to predict HCC prognosis. Our results also provided a framework for understanding the impact of gene expression on the processes of tumorigenesis and clinical outcome.
Highlights
The prognosis of hepatocellular carcinoma (HCC) varies following surgical resection and the large variation remains largely unexplained
On two independent Hong Kong Hepatocellular carcinoma (HCC) cohorts that we previously described [10], the HCC prognosis was significantly associated with clinicopathologic parameters including tumor size, number of tumor nodules (NOTN), tumor stage, venous infiltration status, serum albumin level (ALBU), and serum a-fetoprotein level (AFP)
Clinicopathologic parameters predict HCC prognosis Tumor and adjacent non-tumor liver tissues were collected from 272 Chinese HCC patients who received curative surgery
Summary
The prognosis of hepatocellular carcinoma (HCC) varies following surgical resection and the large variation remains largely unexplained. On two independent Hong Kong HCC cohorts that we previously described [10], the HCC prognosis was significantly associated with clinicopathologic parameters including tumor size, number of tumor nodules (NOTN), tumor stage (new AJCC and pTNM), venous infiltration status, serum albumin level (ALBU), and serum a-fetoprotein level (AFP). These parameters were further summarized into a linear score that was demonstrated to partially predict disease-free survival ([DFS] time to tumor recurrence) and overall survival (time to death) [10]. The search for gene signatures should be conducted by conditioning on the clinicopathologic parameters, and focus on the identification of novel variance components that improve the prognosis prediction beyond that achieved by the clinicopathologic features alone
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