Genetic Secrets of 'Damdoham' Uncovered... "Increased Possibility of Early Diagnosis and Targeted Therapy"

The genetic secrets of the cholangiocarcinoma development process have been uncovered. It is also evaluated that the possibility of early diagnosis and targeted treatment of cholangiocarcinoma through gene panel testing analyzing genomic information has increased.

On the 12th, the National Research Foundation of Korea announced that the research team led by Professors Park Young-nyeon and Kim Sang-woo from Yonsei University College of Medicine succeeded in identifying the genomic and transcriptomic changes from precancerous lesions of cholangiocarcinoma (lesions with a high possibility of progressing to cancer) to invasive cholangiocarcinoma (stage 1 or higher cancer).

A diagram illustrating gene mutations and abnormal gene expression patterns occurring during the development of cholangiocarcinoma from biliary precancerous lesions. Provided by Professor Young-Nyun Park, Yonsei University College of Medicine.

Cholangiocarcinoma is a cancer that occurs in the biliary system (bile ducts and gallbladder), which transports bile produced in the liver. According to data released by the Central Cancer Registry in 2022, the 5-year relative survival rate for cholangiocarcinoma from 2018 to 2022 was only 29.4%. This means that 7 out of 10 patients with cholangiocarcinoma died within 5 years after diagnosis during this period.

On the other hand, cholangiocarcinoma is difficult to detect early due to almost no initial symptoms, and research on gene mutations and expression regulation mechanisms involved in the cancer development process is rare, making early diagnosis and targeted anticancer treatment challenging.

To unravel the genetic secrets of cholangiocarcinoma, the research team first focused on the precancerous lesion with a high possibility of progressing to cholangiocarcinoma, the “biliary papilloma.” They conducted large-scale whole-exome sequencing (analyzing the exon regions that determine amino acid sequences in the human genome) by separating the precancerous lesion area and the invasive carcinoma area infiltrating the surrounding tissue from the tissues of 166 patients diagnosed with papilloma and cholangiocarcinoma.

Among them, data from 41 patients whose biliary papilloma progressed to cholangiocarcinoma were compared and analyzed with the entire patient group, and spatial transcriptome analysis (a method that analyzes gene expression of individual cells within specific tissues combined with their spatial location information) was additionally performed on tumor tissues from 9 patients.

Through this, the research team revealed that the genes mutated in biliary papilloma differ depending on the tumor’s location. They also found that major oncogenic gene mutations occur even before the cancer stage, and that when abnormalities occur mainly in genes related to extracellular matrix changes and growth factor responsiveness, the lesion transforms into cancer that invades surrounding tissues.

Professor Park Young-nyeon of Yonsei University said, “This study is significant as it was conducted on the largest scale among cholangiocarcinoma-related research and produced three-dimensional genetic analysis results to precisely track the carcinogenesis process.” He added, “We expect that the research outcomes will be applied to the development of gene testing panels in the future, contributing to the early diagnosis of cholangiocarcinoma.”

Meanwhile, this research was supported by the Mid-Career Research Program and AI Data-Based Bio-Leading Technology Development Project promoted by the Ministry of Science and ICT and the National Research Foundation of Korea. The research results were published on January 18 in the international journal in the field of gastroenterology and hepatology, the Journal of Hepatology.

This content was produced with the assistance of AI translation services.