Hepatocellular carcinoma (HCC) is well known for poor prognosis and short survival because of high recurrence rate even after curative surgery. Today there is no available
biomarker or biochemical test to indicate HCC recurrence, and this study aims to identify
protein markers that can discriminate postoperative patients with early recurrence (ER), i.e. disease relapsed within the first year. In this study, 103
hepatitis B-related HCC patients were recruited, and 68 of them were used for ER-related
biomarker discovery study. Proteomic expression patterns of matched
tumor and adjacent non-
tumor tissues from these patients plus 16 normal liver tissues were delineated by the two-dimensional gel electrophoresis differential profiling method. Significant
protein spots were evaluated by hierarchical clustering analysis. SSP4612 that yielded the highest receiver operating characteristic (ROC) curve value for the ER subgroup of HCC was subsequently identified by tandem mass spectrometry, and the corresponding expression patterns were further confirmed by quantitative PCR, Western blot, and immunohistochemistry. Correlation analysis with clinicopathological data was also examined. Proteomic profiling analysis revealed overexpression of
mortalin (gene HSPA9) in HCC when compared with the non-
tumor and normal liver tissues (area under the curve (AUC) = 0.821). Furthermore, elevated
mortalin level was also detected in the ER subgroup of HCC versus the recurrence-free state (where no
cancer recurs for >1 year) (AUC = 0.833, sensitivity = 90.9%, specificity = 71.4%). Metastatic HCC cell lines also exhibited higher levels of
mortalin and HSPA9
mRNA. Clinically,
mortalin overexpression in HCC was closely associated with advanced
tumor stages and venous infiltration, having implications for increased
malignancy and aggressive behavior.
Mortalin (HSPA9) is associated with HCC
metastasis and thus suggested as a
tumor marker for predicting early recurrence, which may have immediate clinical applications for
cancer surveillance after curative surgery.