Time: 2024-07-01
A study conducted by researchers from the National Cancer Centre Singapore (NCCS) and A*STAR's Genome Institute of Singapore (GIS) with funding from the National Research Foundation Singapore (NRF) has revealed surprising molecular heterogeneity in liver tumors. The study found that over 40% of Hepatocellular carcinoma (HCC) cases exhibit more than one molecular subtype within the same tumor, with the most aggressive subtype being the best predictor of clinical outcomes. This discovery, known as the "bad apple effect," sheds light on the complexity of Liver cancer and emphasizes the need for comprehensive sampling to enhance the study and treatment of the disease, ultimately improving patient outcomes. The findings were published in the Journal of Hepatology on May 21, 2024.
Liver cancer ranks as the third leading cause of cancer-related deaths in males and the fifth in females in Singapore. HCC, the most prevalent type of primary liver cancer, lacks validated predictive biomarkers, making it challenging for doctors to determine the most suitable treatment for individual patients. This factor contributes to the lower treatment efficacy of HCC compared to other common cancers, with a case-fatality ratio of 0.92, the highest among all cancers in Asians.
To address the clinical gap and enhance HCC treatment, the PLANet study (Precision Medicine in Liver Cancer across an Asia-Pacific Network) analyzed over 600 tumor and adjacent normal samples from 123 HCC patients in Singapore, Malaysia, Thailand, and the Philippines. Utilizing a multi-regional sampling approach, the study delved into the genomic and cellular heterogeneity within each tumor to understand its impact on disease progression. Supported by the NRF and the National Medical Research Council (NMRC) Open Fund-Large Collaborative Grant, administered by the Singapore Ministry of Health, the research aims to advance precision medicine in liver cancer treatment.
The research team uncovered unexpected intratumoral heterogeneity in the HCC transcriptome, revealing the complexity of liver tumor composition. The study highlights the limitation of obtaining a single tumor sample and emphasizes the need for a more comprehensive understanding of the tumor ecosystem to develop effective therapeutics tailored to individual patients. Additionally, more than 40% of HCC samples exhibited multiple transcriptomic subtypes, with the subtype indicating the worst prognosis dictating each patient's clinical outcome. This "bad apple effect" underscores the importance of considering tumor evolution characteristics in predicting patients' survival.
Professor Pierce Chow, the Corresponding Principal Investigator of PLANet 2.0, emphasized the significance of identifying the "bad apple effect" in liver cancer progression as a crucial step towards improving treatment strategies. The application of genomic technologies has enabled researchers to map different cell populations within tumors, facilitating the development of targeted therapies to combat aggressive cells and enhance treatment efficacy. The research team's efforts, supported by a generous S$25 million grant, aim to unravel the complexities of the HCC microenvironment and pave the way for novel treatment discoveries.
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