| Primary liver cancer is one of the most common and aggressive malignancies worldwide and has been the 2nd cancer killer in China since 1990s. The age-standardized mortality rate in China was as high as 34.7/105, which accounted for 53% of all liver cancer deaths worldwide. Although progress has been made in clinical aspect of liver cancer, and some patients with primary liver cancer who was diagnosed and treated at an early stage yielded a curable outcome, however, the overall dismal prognosis has not completely changed. The poor prognosis of liver cancer is largely due to a high rate of recurrence after operation which is mainly resulted from intra-hepatic metastases or vascular invasion.Identifying biomarker with prognostic significance, especially for predicting recurrence has become an important aspect in the hepatocellular carcinoma (HCC) study. Since patients with cancers, particularly with high metastatic potential, tend to have higher levels of DNA in plasma, and the molecular biologic findings of circulating DNA in cancer patients is mimicked to that of cancer cells, plasma DNA may be a candidate because of less invasiveness, simple manipulation, and prognostic information available before operation. Few reports have showed the existence of circulating DNA in HCC patients, and we have recently succeed to detect loss of heterozygosity (LOH) on chromosome 14 (D14S62 and D14S51, which is closely related to metastasis and recurrence of breast cancer) in HCC plasma DNA and found it play an important role in the metastasis and recurrence of HCC patients after operation. However, it is still unclear whether circulating plasma DNA level or its genetic aberrations could be used in predicting the prognosis of HCC patients. In our previous work, we found chromosome 8p deletions might contribute to HCC metastasis. This result was further confirmed by comparison between nude mice models of HCC with different metastatic potentials. With a genome-wide microsatellite analysis of primary and the matched metastatic HCC tissue, a more accurate location was identified on 8p11.2 and 8p23.3. Further more, using the specialized chromosome 8p cDNA microarray, we found 10 expressed sequence tags (ESTs) down-regulate in high-metastatic cell strain MHCC97H with the comparison of low-metastatic cell strain MHCC97L. Among which, a new full-length gene HTPAP was considered to be a new candidate metastatic suppressor for HCC. Therefore, based on our previous work, the objective of this study is to evaluate the diagnostic and prognostic potential of circulating plasma DNA quantification, allelic imbalance (AI) of three microsatellite markers on chromosome 8p [D8S258 (8p11.2), D8S264 (8p23.3) and D8S277 (8p23.1)] and single nucleotide polymorphism (SNP) of HTPAP gene.Part 1. The significance of circulating plasma DNA concentration in patients with hepatocellular carcinoma The objective of this part is to evaluate the possible diagnostic and prognostic values of circulating plasma DNA level in HCC.The peripheral blood samples were collected from 79 HCC patients with normal liver function preoperatively, 20 patients with compensated liver cirrhosis and 20 healthy volunteers. Plasma DNA was extracted and analyzed by ultraviolet transilluminator system. The quantity of plasma DNA was calculated by regression equation which was made by intensity of standard DNA content. Area under curve (AUC) of receiver operator characteristic curve (ROC) was calculated to evaluate the diagnostic efficacy. The relationship between the circulating plasma DNA level and the clinicopathological features and prognosis of HCC patients was investigated.Significant differences (p=0.000; p=0.002) in mean circulating plasma DNA levels were found between healthy volunteers (mean 17.6±9.5 ng/ml) and patients with HCC (mean 47.1±43.7 ng/ml) or liver cirrhosis (mean 30.0±13.3 ng/ml). However, no significant difference of circulating plasma DNA levels could be found between patients with HCC and liver cirrhosis (p=0.191). Among the HCC patient...
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