Clinical and molecular sub-classification of hepatocellular carcinoma relative to alpha-fetoprotein level in an Asia-Pacific island cohort

Abstract

AimIncreased serum alpha-fetoprotein (AFP) levels are associated with specific molecular sub-classes of hepatocellular carcinoma (HCC), supporting AFP as a predictive or therapeutic biomarker for precision treatment of this disease. Considering recent efforts to validate HCC molecular classification systems across different populations, we applied existing signature-based classification templates to Hawaii cohorts and examined whether associations between HCC molecular sub-class, AFP levels, and clinical features found elsewhere can also be found in Hawaii, a region with a unique demographic and risk factor profile for HCC.MethodsWhole-genome expression profiling was performed on HCC tumors collected from 40 patients following partial hepatectomy. Tumors underwent transcriptome-based categorization into 3 molecular sub-classes (S1, S2, and S3). Patient groups based on molecular sub-class and AFP level were then compared with regards to clinical features and survival. Differences associated with AFP level and other clinical parameters were also examined at the gene signature level by gene set enrichment analysis.ResultsStatistically confident (false discovery rate < 0.05) sub-classifications were made in 98% (39/40) of tumors. Patient sub-groups differed significantly with regards to serum AFP level, with significantly lower levels in the S3 sub-group as compared to S1 (P = 0.048) and S2 (P = 0.010). Serum AFP > 400 ng/mL predicted significant tumor enrichment for genes corresponding to MYC target activation, high cell proliferation, poor clinical prognosis, and the S2 sub-class. AFP > 400 ng/mL and non-S3 tumor classification were found to be significant predictors of overall survival.ConclusionDistinct sub-classes of HCC associated with different molecular features and survival outcomes can be detected with statistical confidence in a Pacific Island cohort. Molecular classification signatures and other predictive markers for HCC that are valid for all patient populations are needed to support multi-center efforts to develop targeted therapies for HCC.

Tumor-associated autoantibodies in combination with alpha-fetoprotein for detection of early stage hepatocellular carcinoma

“…AFP performance in this study was within the ranges reported in the literature [62]. It is commonly reported for AFP to have low sensitivity in early stage HCC as AFP is only secreted by certain molecular subtypes of HCC [63], and in those which do, AFP levels positively correlate with tumor size, number, differentiation and vascular invasion [7]. Sensitivity of AFP was low when compared to the TA-AAb panel for stage one HCCs (17% vs 29%) but improved for later stages.…”

Association of Postoperative Biomarker Response with Recurrence and Survival in Patients with Hepatocellular Carcinoma and High Alpha-Fetoprotein Expressions (>400 ng/ml)

“…Importantly, a high AFP expression (>400 ng/mL) is a recognized manifestation of HCC with aggressive biological behavior, and it can also serve as a reflection of tumor burden. 48 , 49 In the present study, clinical characteristics of a specific patient population with HCC with preoperative high AFP levels after curative liver resection were depicted, and their long-term oncologic prognosis and prognostic factors were evaluated. Using the magnitude in decline between preoperative and postoperative serum AFP levels, ie whether a postoperative biomarker response could completely be achieved at the first postoperative follow-up or not, the whole cohort (n=549 patients) was divided into the CBR group (n=456) and the IBR group (n=93).…”

Molecular subtyping of hepatocellular carcinoma: A step toward precision medicine

“…Meanwhile, S3 tumors were smaller, well-differentiated, and overexpressing genes related to liver function (e.g., glycolipid metabolism related genes). With regard to prognosis, up-regulated AFP was associated with aggressive tumor and poor clinical outcome [69]. The S2 subtype was also associated with poor prognosis.…”