A research team led by professor Nam Seok-woo of the Catholic University of Korea has discovered that the driver genes “BANF1, PLOD3, and SF3B4” contribute to the development of early liver cancer.
Liver cancer is one of the three most common carcinomas in the nation, with about 15,000 new cases occurring annually. Liver cancer is the most common cause of cancer death because it is difficult to detect early, and its five-year survival rate is 32.8 percent lower than other cancer cases.
The research team conducted a comparative analysis of the RNA genome data according to the progression stage of liver disease to develop a biomarker capable of early and accurate diagnosis of liver cancer.
As a result, three driver genes, BANF1, PLOD3, and SF3B4, which are activated in the early stage of liver cancer, were derived and proved that this gene is a new marker for the diagnosis of malignant tumors from precancerous lesions, the hospital said.
The team also conducted RNA genomic data analysis and immunohistochemical staining of 813 human tissues from 697 patients with normal liver, precancerous lesions, and hepatocellular carcinoma.
As a result, BANF1, PLOD3, and SF3B4 among 690 genes associated with liver cancer were found to be significantly expressed in precancerous lesions of the pre-liver cancer stage, confirming that it is a “driver gene” that can detect liver cancer by the precancerous lesion.
Also, the hepatocellular carcinoma diagnosis markers (GPC3, GS, HSP70) and the genetic markers (BANF1, PLOD3, SF3B4) identified by Professor Nam resulted in 50.9 percent of the conventional diagnostic markers as positive, and 72.7 percent of the positive diagnostic markers were superior in sensitivity and specificity
|An ultrasonography of hepatocellular carcinoma-infected rats shows a significant decrease in liver cancer and tumor growth rate after being injected with nanoparticles at intervals of two weeks.|
Animal experiments showed that the overexpression of the genes BANF1, PLOD3, and SF3B4 increased hepatocarcinogenesis and inhibited hepatocarcinogenesis during selective inhibition.
Hepatocellular carcinoma-infected rats were injected with nanoparticles loaded with siRNAs inhibiting BANF1, PLOD3, and SF3B4 at intervals of two weeks. The team confirmed the ultrasound results showed a significant decrease in the incidence of liver cancer and tumor growth rate.
Also, SF3B4 has been shown to contribute to the development of liver cancer through abnormal splicing (a process in which unnecessary information is removed from DNA and attached to only necessary data), which causes the loss of function of the tumor suppressor gene KLF4 did.
"Three biomarkers that can detect precancerous lesions that can evolve into malignant tumors for the surgery site where the border between precancerous lesions and malignant tumors are inevitably vague, providing important information that can be specified more accurately,” Professor Nam said.
He went on to say, “The results of this study indicate that it is possible to treat new liver cancer as a therapeutic target. Also, the development of biomarkers that can accurately diagnose liver cancer early is significant because it can significantly improve patient survival."
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