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By 2025, global hepatocellular carcinoma (HCC) incidence is projected to exceed 1 million new cases annually. While HCC is a leading cause of cancer deaths worldwide, its frequency map varies significantly by region.
By 2025, global hepatocellular carcinoma (HCC) incidence is projected to exceed 1 million new cases annually. While HCC is a leading cause of cancer deaths worldwide, its frequency map varies significantly by region.
Globally, the crude rate and ASIR for liver cancer stood at 11.6 and 5.2 per 100,000 population, respectively. (Q Guo · 2024 )
Globally, the crude rate and ASIR for liver cancer stood at 11.6 and 5.2 per 100,000 population, respectively. (Q Guo · 2024 )
HCC risk factors are parallel to sustained liver injury risk factors, i.e., hepatitis B and C, excessive alcohol intake resulting in alcoholic liver disease, lifestyle patterns, and pathological processes leading to non-alcoholic liver disease, among others.
Despite recent great improvements in liver cancer therapeutics such as surgery, chemotherapy, and immunotherapy, this disease remains highly lethal due to its aggressive metastases. Evidence points to the ability of solid tumors to develop multiple invasion and resistance pathways that allow them to circumvent inhibition by a single signaling pathway. In the specific case of HCC, at the time of diagnosis, tumors may be too large or may have encroached on nearby major blood vessels or metastasized, rendering most HCC patients unsuitable candidates for surgical resection.
Identification of factors associated with proliferation in the hepatocellular carcinoma (HCC) micro-environment aids in understanding the mechanisms of disease progression and provides druggable targets. Gene expression profiles of individual cells in HCC and para-carcinoma tissues can be effectively obtained using the single-cell RNA sequencing (scRNA-Seq) technique.
A global frequency map of hepatocellular carcinoma (HCC) incidence in 2025 could show the highest rates in East Asia and Africa, with rising rates in the United States and Europe. While rates in East Asia and Africa may be influenced by chronic viral hepatitis (HBV and HCV), the rising rates in the US and Europe are increasingly linked to non-alcoholic steatohepatitis (NASH).
Projections indicate that globally, there will be over a million cases of liver cancer annually, with hepatocellular carcinoma (HCC) accounting for 75-85% of these cases. The most common causes of HCC globally include HBV, HCV, alcohol-associated liver disease, and metabolic dysfunction-associated steatotic liver disease (MASLD). While HBV infection is a leading cause, NASH is becoming a growing concern.Maintenance of proliferative signaling is a hallmark of cancer. Healthy tissues carefully control their cell growth and division cycle and ensure cell number homeostasis, which preserves tissue architecture and function. Cancer cells emit sustained proliferative signals that activate progression of the cell cycle as well as support the formation and growth of tumor tissue. Although the liver is susceptible to cancer invasion, it is also an organ with the capacity to regenerate after surgical removal or chemical injury. The regenerative process of a normal,healthy liver is predominantly dependent on hepatocyte proliferation, growth, and programmed cell death. The ability to distinguish proliferative hepatocytes from hepatocellular carcinoma (HCC) and normal liver tissues and comparison of their gene expression profiles will aid in understanding the mechanisms underlying aberrant proliferative signaling in malignant cells.
In silico analysis suggests disruption of interactions between HAMP from hepatocytes and SLC40A1 from macrophages in hepatocellular carcinoma. Research shows that HAMP was significantly downregulated in malignant hepatocytes. In addition, a subset of macrophages expressing SLC40A1 and genes reacting to various infections was absent in HCC tissue. These findings support the involvement of HAMP-SLC40A1 signaling in aberrant hepatocyte proliferation in the HCC microenvironment.
Chemotherapy only leads to moderate improvement of the overall survival of patients, due to its lack of specificity as well as the side effects that are often induced as a result of their significant toxicity. Thus, limitations in HCC treatment result in a poor prognosis, and resistance to traditional radiotherapy and chemotherapies. Unfortunately, patients with advanced HCC have a median overall survival below 1 year, and the 5-year recurrence rate of HCC is as high as 70%. The same results (i.e., little effect of chemotherapy, poor prognosis, and treatment resistance) can be seen in other less common types of liver cancers.
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