Priyanshi Patel ’22
Liver cancer is the second most lethal malignancy in the world and includes mainly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). HCC is the most common type of primary liver cancer and often occurs in people with chronic liver diseases. iCCA is also a cancer that develops within the bile duct, whereas HCC occurs among alcoholics or those with fat accumulation in the liver. Cellular diversity within tumors is a key characteristic for therapeutic failures and lethal outcomes of solid malignancies, but no study has yet researched the ecosystem of liver cancer. Numerous scientists from the Laboratory of Human Carcinogenesis studied 19 patients to determine the single-cell transcriptomic landscape of liver cancer biospecimens.
To examine the biodiversity of tumor cells, the scientists generated a droplet-based single-cell RNA sequencing profile of people with HCC and iCCA. Varying amounts of diversity were found in malignant cells within and between tumors and diverse landscapes of tumor microenvironment (TME). Poor survival was associated with high transcriptomic diversity in tumors. Researchers concluded that cellular diversity could be a key contributor towards poor patient responses to molecularly targeted chemotherapeutics. These results may offer insight into liver cancer and its effects on patient prognosis.
This study developed a method that allowed the tumor cell biodiversity to be measured; it demonstrated how tumor transcriptomic diversity, the complete set of RNA transcripts produced in a specific cell, could be associated with patient survival with HCC and iCAA. The results suggest how useful a transcriptomic diversity score could be towards predicting immunotherapy responses. It also provides a rationale for a combination therapy using immune checkpoint blockades and anti-vascular treatments to improve therapeutic efficacy. This study suggests that measuring tumor cell biodiversity would be a practical approach towards determining the shared features of tumor evolution and predicting liver tumor aggressiveness.
- L. Ma, et. al., Tumor cell biodiversity drives microenvironmental reprogramming in liver cancer. CellPress 36, 1-20 (2019). doi: 10.1016/j.ccell.2019.08.007
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