Editor’s Note:
Liver cancer is one of the most prevalent and deadliest cancers in China. Due to the low early diagnosis rate of liver cancer in clinical practice, treatment options such as radical liver resection and transplantation face significant limitations. In recent years, there has been a surge in liver cancer genomics research, providing new insights into early diagnosis, patient stratification, and treatment prognosis. From July 6th to 8th, 2023, the 13th Asia-Pacific Primary Liver Cancer Expert Conference (APPLE 2023) was held in Seoul, South Korea. During the conference, Dr. Xinwei Wang from the U.S. National Cancer Institute gave a special lecture on “The Molecular Landscape and Clinical Significance of Liver Cancer.” Hepatology Digest had the privilege of inviting Dr. Wang to share recent significant developments in this research field and delve into the potential applications and prospects of liver cancer genomics research for early diagnosis and prognosis prediction.
Hepatology Digest: Could you please introduce us to the concept of genomics research in liver cancer? What is its application value in the clinical diagnosis, treatment, and prognosis prediction of liver cancer?
Dr. Wang: Genomics research in liver cancer encompasses DNA sequencing, RNA sequencing, proteomics, and microbiome studies—all of these molecular features fall under genomics research. One of the reasons we conduct all these studies is that liver cancer, especially hepatocellular carcinoma (HCC), is not a single disease but rather a collection of diseases with diverse molecular characteristics. Additionally, liver cancer exhibits extensive tumor heterogeneity. Initially, clinical diagnosis of liver cancer relied heavily on the development of medical imaging, but as clinical practice advanced, we gradually realized that image-based diagnosis was not optimal. Moreover, diagnosing based on histopathological features also had limitations. This is why in recent years we’ve introduced genomics-based approaches as a better way to improve the diagnosis and prognosis of liver cancer patients.
Hepatology Digest: Early detection of liver cancer leads to better treatment outcomes. How can liver cancer be detected early, and can you share some promising research findings in genomics research that have clinical application potential?
Dr. Wang: Early diagnosis of liver cancer is essential for patients to receive the best treatment and prognosis. For these patients, curative treatments such as liver transplantation and liver resection can provide the greatest clinical benefit. Unfortunately, current methods for diagnosing early-stage liver cancer are not ideal. Early diagnosis of liver cancer is achieved by detecting tumor-specific biomarkers produced by tumor cells. While these methods have been in use for years, they are not yet widely applied in clinical practice. Currently, clinical trials related to the early diagnosis of liver cancer are underway to determine whether these biomarkers can yield better results in detecting small tumors. Additionally, we are considering using other alternative indicators to reflect common features of early liver cancer, such as using serum analysis to identify a patient’s history of viral infection. We recently published a study that confirmed this idea—several years before diagnosing liver cancer through imaging, we can detect early liver cancer through characteristics related to a patient’s viral exposure. We believe this could be a potential alternative approach to increasing the detection rate of early liver cancer.
Hepatology Digest: Could you provide an overview of your team’s main research findings in recent years and their clinical significance?
Dr. Wang: Previously, we believed that different stages of liver cancer had varying degrees of metastatic potential. In other words, we thought whether liver cancer would metastasize and recur was not determined at the formation of the primary tumor but evolved over time. However, unfortunately, this initial theory was flawed. In recent years, our team has discovered through continuous research that a tumor’s invasiveness is inherent, contrasting with the previous understanding of tumor recurrence. With the deepening of genomics research, we’ve come to understand that a tumor’s metastatic potential is “embedded” in its DNA from the very beginning of tumor development. As the tumor grows and evolves, it will eventually metastasize. Identifying the key genes that determine tumor invasiveness and intervening can help us prevent tumor recurrence and improve long-term patient outcomes. Additionally, this new understanding of tumor metastasis and recurrence will aid in patient stratification and clinical treatment decisions for liver cancer patients. These findings have epoch-making significance.
Hepatology Digest: What do you think will be the main research directions for liver cancer genomics in the future? What challenges will we face?
Dr. Wang: Currently, the most significant challenges in the clinical management of liver cancer are tumor recurrence and treatment resistance, which are also our main research directions. We often see that many early-stage liver cancer patients, despite undergoing curative treatments like liver resection or transplantation, still face the risk of tumor recurrence. In advanced liver cancer patients, although the efficacy of targeted therapy and immunotherapy has significantly improved, the probability of tumor recurrence remains high. Many liver cancer patients do not respond to targeted therapy or immunotherapy due to the continuous evolution of the tumor. Ultimately, the continuous evolution of tumors may be the primary challenge we face, and it is a critical issue that requires in-depth research. Only when we truly understand the key molecules and mechanisms driving tumor evolution can we further enhance the effectiveness of liver cancer treatment and improve long-term patient survival.
