Researcher Takes Steps to Develop a Non-invasive Early Detection Test For Liver Cancer

Surbhi Jain, PhD, is a postdoctoral researcher at Drexel University in Philadelphia, PA, who received a fellowship from the Foundation in spring 2009. As a fellow, Dr. Jain researched the development of a urine test for the early detection of liver cancer. This month we caught up with her to learn more about her research and the importance of funding studies in prevention and early detection.

1. What led you to the field of liver cancer research?

My first tryst with cancer started in textbooks of pathology and continued on to my hospital ward rounds as a medical student in India. By the time I was an intern, I understood why cancer is the most challenging disease of our times. Even in modern state-of-the-art medical facilities, there was only so much you could do to fight an advanced-stage tumor. I realized that current anti-cancer therapy, even if it is successful, is a traumatic and a heart-wrenching experience. That understanding steered me to work in the field of cancer research, particularly in early detection.

I was driven towards liver cancer research after joining Dr. Ying-Hsiu Su’s laboratory, who is also my mentor. I work as a postdoctoral fellow at the Drexel Institute of Biotechnology & Viral Research at the PA Biotech Center. Liver cancer is the fifth most frequently occurring cancer in the world and is the third leading cause of cancer mortality. It is responsible for between 250,000 and 800,000 deaths per year globally. It is an aggressive cancer with a poor prognosis; the 5 year survival rates are usually less than 5% following diagnosis using conventional methods of detection and treatment. Surgical and chemotherapeutic intervention can improve the prognosis, only if early detection is done. Unfortunately, it is nearly impossible to detect hepatocellular carcinoma (HCC), the most common type of liver cancer, early using current methods of detection. Thus, there is a clear and urgent need for non-invasive, reliable methods for the early detection of HCC. Dr. Su has previously shown that urine contains DNA from the circulation that carries tumor specific signatures. This finding coupled with the right molecular technology could be used to develop a urine based screening test for liver cancer.

2. Tell us about your research to develop a urine test for the early detection of liver cancer.

The overall objective is to develop non-invasive urine tests for the early detection of HCC that will improve the prognosis and survival rate. Urine contains fragmented DNA that is derived from circulating blood. This also includes apoptotic DNA from non-urinary tract tumors such as liver cancer. The goal of my research is to develop a urine-based assay for detecting such tumor-derived DNA. Given the heterogeneity in the genetic makeup of liver cancer, we want to assemble a panel for various genetic mutations and epigenetic modifications, i.e. genes modified by DNA methylation. We first identified potential DNA markers based on literature research and performed comprehensive methylation mapping to identify liver cancer specific methylation sites in these candidate genes using patient tissue samples. We then designed assays to test these markers in a larger study group and analyze their sensitivity, specificity, and ability to accurately detect cancer (ROC curves). We have discovered, to the extent examined, liver-specific methylation patterns and have mapped HCC-specific epigenetic patterns for the APC, GSTP1 and RASSF1a genes. These results not only identified HCC-specific CpG sites but also explained why the HCC specificity of these markers varied in previous studies. We have shown that by combining 4 DNA markers, we obtain 93% accuracy in distinguishing liver cancer from cirrhosis and hepatitis in tissue and identify 92% of AFP-negative HCC tissues in our study population. The discovery of our markers for the AFP-negative HCC is very important since there is currently no biochemical biomarker for AFP-negative HCC. These findings are essential to develop highly sensitive and specific assays for each marker. Currently, we are working on developing assays that are optimized for the small fragmented urine DNA and testing them in urine samples collected from patients.

Read Part II of Dr. Jain’s Researcher Q&A!