Circulating Cell-free DNA as a Predictive Biomarker for Hepatocelluar Carcinoma.

Overview

Circulating free cell DNA (cfDNA) is extracellular fragmentation of nucleic acids that occurs both in plasma and serum. This kind of DNA which derived from the apoptotic/necrotic cells or the lysis of circulating tumor cells (CTCs) can be detectedin the patients with a variety of diseases. Emerging evidence suggests that cfDNA from patients exhibits characteristicchanges of tumors, suchas mutations, insertions/deletions, methylations,microsatellite aberrations, and copy number variations, etc. All of these reveal a visible difference between the benign conditions, and thus may be useful in the diagnosis of cancer, identification of targeted therapy, monitor responses to treatments, and early detection of relapse. The purpose for this study is to explore these characteristic changes in the patients withhepatocellular carcinoma (HCC) and expect to guide targeted therapy and identify non-invasive biomarkers of cancer diagnosis and prognosis which can be easily isolated from the circulation.

In cancer, cfDNA can be detected a higher concentration in the circulation because of the necrosis of neoplasm cells with the rapid enlargement and relatively shortage of blood supply. So, identifying tumor-specific genetic and epigenetic changes in cfDNA on this status, such as gene mutations, deletions, methylation alterations and microsatellite alterations, may be more specific for us to diagnose the neoplasms in early phase. This phenomenon also appears in the patients with hepatocellular carcinoma (HCC). Studies have shown that cfDNA level is associated with intrahepatic and extrahepatic metastasis in HCC patients and examined some cfDNAcharacteristic changes, such as p161NK4A, RTL, RASSF1A, LINE-1 and GSTP1. Thus is useful for us to explore the specific cfDNA in HCC. For a high sensitivity and specificity detection, we will use technologiesdeveloped at Stanford Genome Technology Centerto find more characteristic gene mutations, methylation alterations or other changes (3). In this study, we willinvestigate thesecharacteristic changesin cfDNA and primary tumor lesions. Study arrangement: Collect the DNA samples from the plasma, blood cells and solid tumor tissues in the patients with HCC. Detect the DNA sequence from the samples of plasma, blood cells and solid tumor tissues. Identify cancer specific variations in cfDNA and primary tumor lesions. Date analysis and investigate these characteristic changes. Evaluate the application in early diagnosis, treatment monitoring and prognosis for HCC.