Cancer Cell: Fan Jia/Zhou Hu and others draw a panoramic view of the multi-omics molecular features of intrahepatic cholangiocarcinoma

Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver malignant tumor.
The current surgical resection rate is low and there is a lack of effective targeted/immunotherapy options
.

Intrahepatic cholangiocarcinoma has a highly heterogeneous genome mutation and tumor microenvironment, which may mediate its high aggressiveness and poor prognosis

On December 30, 2021, Academician Fan Jia of Zhongshan Hospital Affiliated to Fudan University, Researcher Zhou Hu of Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and Researcher Gao Daming of the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, jointly published the title: Proteogenomic in Cancer Cell, a top international oncology journal characterization identifies clinically relevant subgroups of intrahepatic cholangiocarcinoma
.

On December 30, 2021, Academician Fan Jia of Zhongshan Hospital Affiliated to Fudan University, Researcher Zhou Hu of Shanghai Institute of Materia Medica, Chinese Academy of Sciences, and Researcher Gao Daming of the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, jointly published the title: Proteogenomic in Cancer Cell, a top international oncology journal characterization identifies clinically relevant subgroups of intrahepatic cholangiocarcinoma
.

The study performed protein genomics analysis on the tumor tissues of 262 patients with intrahepatic cholangiocarcinoma (iCCA).
By integrating multi-dimensional data such as genome, transcriptome, proteome, and phosphorylated proteome, it helped the development of intrahepatic cholangiocarcinoma.
Mechanisms, molecular classification, prognostic monitoring and personalized treatment strategies provide new ideas
.

On the one hand, the research fully revealed the impact of gene mutations and chromatin variations in intrahepatic cholangiocarcinoma on the proteome and phosphorylated proteome.
Four molecular types and biomarkers were proposed from the proteome level to explore tumor heterogeneity.
Sexuality and the realization of individualized treatment provide clues; on the other hand, the high-quality big data generated by the research will continue to provide support for basic and clinical research on intrahepatic cholangiocarcinoma
.

Researchers first analyzed the effects of major driving mutations in intrahepatic cholangiocarcinoma such as TP53, KRAS, FGFR2, IDH1/2, and BAP1 on the proteome and phosphorylated proteome
.

The study found that there are specific aflatoxin mutation fingerprints in Chinese population samples, which are significantly related to high tumor mutation burden and high NK cell infiltration

Subsequently, the joint team further analyzed the cis and trans regulatory effects of chromatin copy number variation in intrahepatic cholangiocarcinoma on mRNA and protein
.

Researchers divide iCCA patients into four subtypes: inflammation (S1), mesenchyme (S2), metabolism (S3), and differentiation (S4) based on proteomic data.

Through dimensionality reduction analysis, the team found a marker that can specifically distinguish the four subtypes, and verified the possibility of its use in clinical sample typing
.

In the end, researchers determined that HKDCl and SLC16A3 are biomarkers related to the prognosis of iCCA

This research is carried out under the framework of high quality standards of the International Cancer Proteogenome Consortium (ICPC) and the International Clinical Proteomic Tumor Analysis Consortium (CPTAC) for intrahepatic cholangiocarcinoma.
Cohort of protein genomics analysis
.

Analysis of protein genomics of intrahepatic cholangiocarcinoma

Protein genomics analysis of intrahepatic cholangiocarcinoma

On the one hand, the research fully revealed the impact of gene mutations and chromatin variations in intrahepatic cholangiocarcinoma on the proteome and phosphorylated proteome.
Four molecular types and biomarkers were proposed from the proteome level to explore tumor heterogeneity.
Sexuality and the realization of individualized treatment provide clues; on the other hand, the high-quality big data generated by the research will continue to provide support for basic and clinical research on intrahepatic cholangiocarcinoma
.

On the one hand, the research fully revealed the impact of gene mutations and chromatin variations in intrahepatic cholangiocarcinoma on the proteome and phosphorylated proteome.
Four molecular types and biomarkers were proposed from the proteome level to explore tumor heterogeneity.
Sexuality and the realization of individualized treatment provide clues; on the other hand, the high-quality big data generated by the research will continue to provide support for basic and clinical research on intrahepatic cholangiocarcinoma
.

Dr.
Dong Liangqing, Zhongshan Hospital Affiliated to Fudan University, Lu Dayun, PhD candidate at Shanghai Institute of Materia Medica, Chen Ran, Ph.
D.
candidate at the Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, Lin Youpei, Ph.
D.
candidate at Zhongshan Hospital, Fudan University, Zhu Hongwen, Associate Researcher, Shanghai Institute of Materia Medica, Zhang Dr.
Zhou and Dr.
Cai Shangli are the co-first authors of this article
.

Academician Fan Jia, Researcher Zhou Hu, Researcher Gao Daming and Professor Gao Qiang are the co-corresponding authors of this article

Original source:

Original source:

Liangqing Dong, et al.

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