When many people are diagnosed with liver cancer, the course of the disease has often entered the middle and late stages, which is why it is extremely important to emphasize early screening and early diagnosis. (Shutterstock)
In the era of precision treatment, can liver cancer be like lung cancer, breast cancer and other cancers, with genetic testing, targeted drugs or immune drugs can greatly improve the survival rate?
Why Liver Cancer Screening Should Be Done Early
Liver cancer refers to malignant tumors in the liver, the most common being hepatocellular carcinoma. Hepatocellular carcinoma (referred to as “liver cancer”, HCC) accounts for about 90% of primary liver cancers. It is the sixth most common tumor and the third leading cause of cancer death in the world, and it is also the fastest-growing cancer in the United States. According to 2015 data, China’s new patients and deaths account for more than half of the world’s total.
Due to the hidden onset of liver cancer, most of them are found in the middle and late stages. Patients with early-stage liver cancer can receive radical treatment, including resection, ablation therapy, and liver transplantation. The 5-year survival rate exceeds 70%. However, patients with advanced liver cancer can only receive palliative systemic treatment, and the 5-year survival rate is less than 5%. Therefore, early screening for people at risk of liver cancer is extremely important.
Which high-risk groups should be screened
There are many risk factors for liver cancer, among which patients with chronic hepatitis B virus and hepatitis C virus infection account for 85% of liver cancer cases worldwide.
Other risk factors include metabolic disorders such as nonalcoholic fatty liver disease and chronic alcohol use. Another estimate is that the incidence of liver cancer in patients with cirrhosis is 2-4% per year.
The current liver cancer screening recommendations endorsed by professional association guidelines suggest that patients with liver cirrhosis and chronic hepatitis B virus infection should undergo abdominal ultrasonography every six months and undergo blood tests to measure whether serum alpha-fetoprotein (AFP) exceeds the standard.
Limitations of Ultrasound Screening – A Challenge for Early Diagnosis
However, early screening has limitations. A meta-analysis reported that the sensitivity of ultrasound for the detection of early liver cancer was only 45%. Furthermore, cirrhosis and obesity, which are more prevalent in Western patients compared with Asians, also reduce the sensitivity of abdominal ultrasonography.
On the basis of ultrasound, after adding the biomarker AFP (serum alpha-fetoprotein, also known as fetal protein) detection, the sensitivity of ultrasound detection is increased to 63%.
Fetal protein can be tested by drawing blood. “Fetal protein” (AFP) in serum is used as a tumor marker for liver cancer. If the marker exceeds the normal standard, further examinations are required to confirm whether you have liver cancer.
At present, the diagnosis of liver cancer mainly relies on imaging examinations, including ultrasound scans, computed tomography, angiography, MRI examinations, and sometimes liver tissue or liver puncture.
Since many people are diagnosed with liver cancer, the course of the disease has often entered the middle and late stages, which is why it is extremely important to emphasize early screening and early diagnosis. Currently, researchers focus their hopes for early diagnosis of liver cancer on the research and use of tumor biomarkers.
Biomarkers for early diagnosis of liver cancer
In the early detection of liver cancer, AFP is the most commonly used biomarker, and it is also the only clinically validated biomarker. AFP is a part of the serum albumin gene family. The synthesis of AFP in the liver occurs during the fetal period, usually declines rapidly after the fetus is born, and remains at a low level throughout adulthood.
However, AFP alone is not enough to diagnose liver cancer because it is elevated in certain other conditions in the body, such as pregnancy, chronic liver disease, liver cancer, germ cell tumors and stomach cancer. Knowing that the available biomarkers for detection of early liver cancer have been explored, experts believe that for liver cancer, the ultimate goal of tumor biomarkers should be to promote early diagnosis of liver cancer and reduce mortality.
Other candidate biomarkers for early diagnosis include osteopontin (OPN), vascular endothelial growth factor (VEGF), angiopoietin 2 (ANG-2), Golgi protein 73 (Gp-73), insulin growth factor- 1 (IGF-1), liver growth factor (HGF), Glypican-3 and c-MET, etc., their sensitivity or specificity need to be further verified.
At present, tumor gene detection (biomarker detection) is an essential part of precision treatment. Cancers such as lung cancer and breast cancer generally require genetic detection before considering the selection of drugs or immunotherapy with corresponding targets. However, the pathogenesis of liver cancer is relatively complex, and there are few gene mutations that cause cancer, so the treatment methods are also very different.
Surgical resection, ablation, or liver transplantation are often used for early and mid-stage liver cancer, and palliative treatments are used for those who are inoperable in the later stage, including targeted therapy or immunotherapy. Due to the lack of driving genes that cause liver cancer, most targeted drugs usually target VEGF/VEGFR targets to interfere, destroy, and block the blood vessels that supply nutrients and oxygen to liver cancer cells, that is, “starve” cancer cells. cells, does not directly target tumor cells, nor does it involve mutated genes. Therefore, if targeted therapy is used for liver cancer, genetic testing is generally not required except in special circumstances.
For patients with advanced inoperability, genetic testing is used to determine whether immunotherapy can be used. Currently, the three conventional biomarkers that can predict the efficacy of immunotherapy are PD-L1, TMB and MSI.
In addition to the above three markers, there are some specific gene variations that may be associated with immunotherapy hyperprogression. Hyperprogression refers to the phenomenon that some patients not only do not benefit from immunotherapy, but instead experience rapid disease progression.
Through genetic testing, it is not only possible to predict the efficacy of immunotherapy, but also to assess whether a patient has a gene with a risk of hyper-progression, so as to achieve precise immunotherapy and save patients from going the wrong way.
If you want to know more about biomarker detection, please check here:https://www.epochtimes.com/b5/ncid1518384.htm。◇
The main reference sources for this article:
https://www.journal-of-hepatology.eu/article/S0168-8278(22)03067-7/fulltext
Editor in charge: Li Fan◇
