Background: We investigated the genotypic distribution of Hpdel in healthy subjects and cancer patients in Taiwan.
Methods: Blood samples were collected from 244 randomly selected healthy Taiwanese volunteers and 737 patients with various cancers. Samples were analyzed for the haptoglobin (Hp) gene, and the presence of the Hpdel allele was determined from genomic DNA by an Hpdel-specific polymerase chain reaction (PCR) method. The plasma concentration of Hp was also determined.
Results: The frequency of the Hpdel allele was calculated to be 0.029, and was not different between the healthy subjects and patients with cancer. The prevalence of Hp deficiency caused by Hpdel homozygosity was estimated to be ∼0.85 in 1000. Fifty-seven subjects were reclassified from homozygous Hp1 or Hp2 to Hp1/Hpdel or Hp2/Hpdel genotypes. The Hpdel allele is not associated with prevalence, severity or stage of any cancer.
Conclusions: Congenital Hp deficiency caused by Hpdel homozygosity is a condition present in Taiwan with a relatively high frequency. However, the Hpdel variant does not play a role in cancer.
Background: Aberrant DNA methylation is associated with the development of hepatocellular carcinoma (HCC), suggesting that gene methylation could be a potential biomarker for detection of HCC. The aim of this study is to identify potential biomarkers in HCC.
Methods: We used the Infinium methylation array and a DNA-pooling strategy to analyze the genome-wide methylation profile in HCC. Quantitative methylation-specific PCR (Q-MSP) was used to validate homeobox A9 (HOXA9) methylation in 29 normal controls, 100 HCC samples and adjacent non-tumor tissues and in 74 plasma samples, including 40 patients with HCC.
Results: Ten genes (HOXA9, NEUROG1, TNFRSF10C, IRAK3, GFPT2, ZNF177, DPYSL4, ELOVL4, FSD1, and CACNA1G) showed differences in methylation between controls and HCCs. Of these, HOXA9 was significantly hypermethylated in HCCs (76.7%; 23/30) compared with controls (3.4%; 1/29). In addition, combination analysis of two- and three-gene sets for HCC detection showed greater sensitivity (90%–96.7%) and comparable specificity (93.1%–96.6%) to each individual gene (33.3%–76.7% and 55.2%–100.0%). HOXA9 methylation was further validated by Q-MSP in two independent set of clinical samples including 100 HCC and paired non-tumor tissues. Further, HOXA9 methylation could be detected in plasma from HCC patients (n=40) but not in normal plasma (n=34) (p<0.0005). Combined testing (either parameter positive) for α-fetoprotein (AFP, a plasma protein biomarker) and HOXA9 methylation showed greater sensitivity (94.6%) for detection of HCC than AFP alone (75.7%).
Conclusions: These data suggest that methylation of HOXA9 could be a helpful biomarker to assist in HCC detection.