A team of Xi'an Jiaotong University (XJTU) has achieved a significant triumph in the pathogenesis of intrahepatic cholangiocarcinoma (ICC), which was published in Hepatology, a world-famous journal devoted to liver disease. 

The research results were published in a paper entitled Cellular heterogeneity and transcriptomic profiles during intrahepatic cholangiocarcinoma initiation and progression. (Link to the paper: https://aasldpubs.onlinelibrary.wiley.com/doi/full/10.1002/hep.32483)

The first authors of the paper are doctoral student Wang Tingjie from the School of Automation Science and Engineering and Professor Xu Chuanrui from Huazhong University of Science and Technology (HUST).

The research had the support of the following three XJTU groups: the single-cell sequencing team of the First Affiliated Hospital of XJTU, the XJTU Med-X Academy and the XJTU Bioinformatics Institute. 

The researchers indicate that ICC, the second most common primary liver malignancy after hepatocellular liver cancer, is characterized by high invasiveness, poor prognosis and so forth, and has an increasing incidence. However, when it comes to the effectiveness of targeted and immunotherapy for ICC, its insidious onset and high heterogeneity are considered the critical factors.

The research team led by XJTU Professor Ye Kai and HUST Professor Li Lei, with an ICC mouse model, made great contributions to the analysis of the dynamic heterogeneity within tumor tissues at different stages of ICC, using diverse means of collecting time-series single-cell transcriptome data, integrating multidimensional histological data, and analyzing and verifying the dynamic interactions of key regulatory networks, early origin cells, key driver genes, and endothelial fibroblasts in tumor heterogeneity during tumor development.

In the study, stress-responsive and proliferative tumor subtypes were identified in ICC tumor cells. Moreover, with machine learning methods such as gene co-expression and graph network mining, the researchers made three new discoveries of worldwide impact, identifying the heterogeneous transcription factors and regulatory networks in the two tumor subtypes, the key driver genes in the process of differentiation to carcinogenesis of epithelial cells within the liver and the dynamic process and molecular mechanism by which apical endothelial cells promote fibroblast remodeling in response to fibroblast stimulation and ultimately promote tumor cell proliferation.

Not only does the research further the understanding of the pathogenesis, diagnosis, and intratumoral heterogeneity of ICC, but brings to light new possibilities for treatment.