DNALI1 expression and gene polymorphism are associated with disease recurrence after curative surgery in hepatocellular carcinoma

Abstract

Dynein, axonemal, light intermediate polypeptide 1 (DNALI1) expression was found to significantly associate with disease recurrence (hazard ratio 1.7, P=0.014) from our earlier genome-wide expression study by cDNA microarray approach on hepatocellular carcinoma (Mol Biol Cell 2002). To consolidate the prognostic significance of DNALI1 expression, we examined the second sample set (n=50) and employed quantitative RT-PCR as an independent research method to measure the transcript level in comparison to microarray quantitation with the aim to determine the DNALI1 level. The association of a higher DNALI1 expression level with early disease recurrence was again confirmed (P=0.045). From the sequence database, DNALI1 revealed a polymorphism at nucleotide 194 (codon 65), which either harbored the C-allele (GCA, alanine) or T-allele (GTA, valine). We then further examined the paralleled blood samples of the patients for gene polymorphism. The tumor DNALI1 transcript level was significantly higher in patients with T-allele compared to patients with C-allele (2.4 fold, P=0.029). DNALI1 reveals the potential as a useful molecular marker, as it provides prognostic information in general (two independent cohorts of patients) and the prediction is independent of the assay method (microarray or quantitative RT-PCR). Furthermore, the DNALI1 transcript level is associated with gene polymorphism. The biological contribution of DNALI1 for poor prognosis is unknown and warrants further investigation.