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Intrahepatic cholangiocarcinoma is the second most common primary liver malignancy, with difficult early diagnosis, low surgical resection rate, high malignancy, easy involvement of peripheral organs and distant metastasis, insensitivity to radiotherapy and chemotherapy, and poor prognosis.
The 5-year survival rate after surgery is only 20% to 30%, and there is a lack of effective targeted and immunotherapy
.
Therefore, it is urgent to elucidate the pathogenesis of intrahepatic cholangiocarcinoma and to draw more accurate gene and molecular maps to provide a theoretical basis for identifying new targets for diagnosis and treatment and realizing individualized treatment
.
On December 30, 2021, the world's top biomedical journal "Cancer Cell" published online the latest results of the team of Academician Fan Jia from the Liver Cancer Research Institute of Fudan University (Affiliated Zhongshan Hospital) "Proteogenomic profiling and clinical subtypes of intrahepatic cholangiocarcinoma".
The research paper comprehensively analyzed the molecular characteristics of intrahepatic cholangiocarcinoma, and provided new ideas and strategies for the clinical diagnosis and treatment of intrahepatic cholangiocarcinoma
.
Academician Fan Jia and other teams collaborated to synthesize multi-omics and multi-dimensional data such as genome, transcriptome, proteome, phosphorylated proteome, and microbiome using samples from 262 patients with intrahepatic cholangiocarcinoma resected in liver surgery at Zhongshan Hospital.
For the first time, the multi-dimensional molecular map of intrahepatic cholangiocarcinoma was systematically drawn, which provided new ideas for the occurrence and development mechanism, precise molecular typing, prognosis judgment and personalized treatment strategy of intrahepatic cholangiocarcinoma
.
In this study, the team of Academician Fan Jia established the molecular typing of intrahepatic cholangiocarcinoma patients with proteome as the core: inflammatory type (S1), interstitial type (S2), metabolotype (S3) and differentiated type (S4).
, these four subtypes have unique characteristics in terms of genome, immune microenvironment, treatment strategy, clinical prognosis, etc.
, and are expected to guide clinical individualized diagnosis and treatment; and five main driving genes of intrahepatic cholangiocarcinoma (TP53, KRAS, The targeted potential therapeutic targets of FGFR2, IDH1/2, BAP1) have deeply revealed the correlation of these mutations with biological processes such as cell cycle, drug metabolism, and inflammation-infection
.
In addition, the study revealed the important role of gene mutation fingerprints caused by aflatoxin and Chinese herbal medicine aristolochic acid in the occurrence and development of intrahepatic cholangiocarcinoma, providing clues for etiological prevention
.
In particular, it was found that 10% of intrahepatic cholangiocarcinomas have FGFR2 gene fusions and mutations.
FGFR2 fusion proteins not only drive the occurrence and development of intrahepatic cholangiocarcinoma and generate new targeted therapy targets, but also some fusion protein-derived antigenic peptides It has strong immunogenicity, can cause activation and expansion of specific T cell populations, and is also a potential immunotherapy target
.
This research is another masterpiece by the team of Academician Fan Jia after the molecular typing of hepatocellular carcinoma topped the international top journal Cell in 2019, and the early hepatocyte proteome in collaboration with the team of Academician He Fuchu topped Nature in 2019
.
Through the integration of multi-omics data, the molecular characteristics and occurrence and development mechanism of intrahepatic cholangiocarcinoma are relatively completely revealed.
It is a powerful combination of clinical science and basic science such as proteomics.
make breakthroughs
.
These achievements will further expand China's advantages in the field of precision medicine, promote the innovative development of the biomedical industry, and make important contributions to the exploration of tumor heterogeneity and the realization of individualized treatment
.
Academician Fan Jia of Zhongshan Hospital Affiliated to Fudan University, Zhou Hu, researcher of Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Gao Daming, researcher of Center for Excellence in Molecular and Cell Science, Chinese Academy of Sciences, and Professor Gao Qiang of Zhongshan Hospital are the co-corresponding authors of this article.
.
Physician Dong Liangqing of Zhongshan Hospital, Lu Dayun and Chen Ran, doctoral students of the Chinese Academy of Sciences, are the co-first authors of the article
.
Source: Official public platform of Zhongshan Hospital Affiliated to Fudan University
The 5-year survival rate after surgery is only 20% to 30%, and there is a lack of effective targeted and immunotherapy
.
Therefore, it is urgent to elucidate the pathogenesis of intrahepatic cholangiocarcinoma and to draw more accurate gene and molecular maps to provide a theoretical basis for identifying new targets for diagnosis and treatment and realizing individualized treatment
.
On December 30, 2021, the world's top biomedical journal "Cancer Cell" published online the latest results of the team of Academician Fan Jia from the Liver Cancer Research Institute of Fudan University (Affiliated Zhongshan Hospital) "Proteogenomic profiling and clinical subtypes of intrahepatic cholangiocarcinoma".
The research paper comprehensively analyzed the molecular characteristics of intrahepatic cholangiocarcinoma, and provided new ideas and strategies for the clinical diagnosis and treatment of intrahepatic cholangiocarcinoma
.
Academician Fan Jia and other teams collaborated to synthesize multi-omics and multi-dimensional data such as genome, transcriptome, proteome, phosphorylated proteome, and microbiome using samples from 262 patients with intrahepatic cholangiocarcinoma resected in liver surgery at Zhongshan Hospital.
For the first time, the multi-dimensional molecular map of intrahepatic cholangiocarcinoma was systematically drawn, which provided new ideas for the occurrence and development mechanism, precise molecular typing, prognosis judgment and personalized treatment strategy of intrahepatic cholangiocarcinoma
.
In this study, the team of Academician Fan Jia established the molecular typing of intrahepatic cholangiocarcinoma patients with proteome as the core: inflammatory type (S1), interstitial type (S2), metabolotype (S3) and differentiated type (S4).
, these four subtypes have unique characteristics in terms of genome, immune microenvironment, treatment strategy, clinical prognosis, etc.
, and are expected to guide clinical individualized diagnosis and treatment; and five main driving genes of intrahepatic cholangiocarcinoma (TP53, KRAS, The targeted potential therapeutic targets of FGFR2, IDH1/2, BAP1) have deeply revealed the correlation of these mutations with biological processes such as cell cycle, drug metabolism, and inflammation-infection
.
In addition, the study revealed the important role of gene mutation fingerprints caused by aflatoxin and Chinese herbal medicine aristolochic acid in the occurrence and development of intrahepatic cholangiocarcinoma, providing clues for etiological prevention
.
In particular, it was found that 10% of intrahepatic cholangiocarcinomas have FGFR2 gene fusions and mutations.
FGFR2 fusion proteins not only drive the occurrence and development of intrahepatic cholangiocarcinoma and generate new targeted therapy targets, but also some fusion protein-derived antigenic peptides It has strong immunogenicity, can cause activation and expansion of specific T cell populations, and is also a potential immunotherapy target
.
This research is another masterpiece by the team of Academician Fan Jia after the molecular typing of hepatocellular carcinoma topped the international top journal Cell in 2019, and the early hepatocyte proteome in collaboration with the team of Academician He Fuchu topped Nature in 2019
.
Through the integration of multi-omics data, the molecular characteristics and occurrence and development mechanism of intrahepatic cholangiocarcinoma are relatively completely revealed.
It is a powerful combination of clinical science and basic science such as proteomics.
make breakthroughs
.
These achievements will further expand China's advantages in the field of precision medicine, promote the innovative development of the biomedical industry, and make important contributions to the exploration of tumor heterogeneity and the realization of individualized treatment
.
Academician Fan Jia of Zhongshan Hospital Affiliated to Fudan University, Zhou Hu, researcher of Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Gao Daming, researcher of Center for Excellence in Molecular and Cell Science, Chinese Academy of Sciences, and Professor Gao Qiang of Zhongshan Hospital are the co-corresponding authors of this article.
.
Physician Dong Liangqing of Zhongshan Hospital, Lu Dayun and Chen Ran, doctoral students of the Chinese Academy of Sciences, are the co-first authors of the article
.
Source: Official public platform of Zhongshan Hospital Affiliated to Fudan University
