Anuradha Budhu, Ph.D., heads a research team at the National Cancer Institute that recently uncovered an imbalance between saturated and unsaturated fats (such as palmitic or fatty acids) that occur in patients with a common liver cancer called hepatocellular carcinoma, or HCC. Budhu’s team also determined that HCC patients with high unsaturated fat levels had poor survival rates, suggesting that a shift of balance toward saturated fats may be a novel therapeutic strategy in the treatment of aggressive liver cancer.
Budhu, who earned her doctorate at Cornell University, is a staff scientist at NCI’s Center for Cancer Research. She has been awarded CCR’s outstanding postdoctoral award as well as the NCI Director’s Innovation Award.
She has been in the Laboratory of Human Carcinogenesis since 2002 working to uncover molecular and genomic targets associated with liver cancer and its metastasis. Using these techniques in a unique way, she and her colleagues were able to link fatty acids with HCC patient outcome.
Past studies on HCC focused on the roles of either genes or metabolites, which are byproducts of metabolism such as fatty acids. Budhu’s group was the first to interweave these two distinct platforms to search for the key molecular drivers of HCC. As a result, they uncovered a set of cellular alterations in fat signaling pathways associated with HCC and discovered that an important transmitter of fatty acid flow—a gene called stearoyl CoA-desaturase, or SCD, that contributed to unfavorable outcomes for HCC patients. The study findings were published in Gastroenterology.
To profile metabolite and gene signals in HCC, Budhu and her colleagues worked with tissue samples taken from 386 HCC clinical patients that they divided into three sets—training, test and validation. Using the training set, they profiled paired tumor and non-tumor samples to identify the interdependent metabolites and genes in a HCC subtype that is most often associated with poor patient survival.
Once these molecular targets were identified, they searched for key pathways that connected these metabolites and genes, which they then confirmed in test and validation tissue sample sets for accuracy. As a result, they found that SCD and its associated metabolite—unsaturated fat—were associated with aggressive HCC outcomes. While these integrative results have shown that SCD and its related metabolites may one day be valuable as biomarkers and prognostic indicators for HCC, more work is needed to determine the mechanism underlying SCD’s role in HCC, said Budhu.Print This Post