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ToolsDong, Liangqing, Lu, Dayun, Chen, Ran, Lin, Youpei, Zhu, Hongwen, Zhang, Zhou, Cai, Shangli, Cui, Peng, Song, Guohe, Rao, Dongning, Yi, Xinpei, Wu, Yingcheng, Song, Nixue, Liu, Fen, Zou, Yunhao, Zhang, Shu, Zhang, Xiaoming, Wang, Xiaoying, Qiu, Shuangjian, Zhou, Jian, Wang, Shisheng, Zhang, Xu, Shi, Yongyong, Figeys, Daniel, Ding, Li, Wang, Pei, Zhang, Bing, Rodriguez, Henry, Gao, Qiang, Gao, Daming, Zhou, Hu and Fan, Jia (2022) Proteogenomic characterization identifies clinically relevant subgroups of intrahepatic cholangiocarcinoma. Cancer Cell, 40 (1). pp. 70-87. ISSN 1535-6108
Full text not available from this repository. (Request a copy)Abstract
We performed proteogenomic characterization of intrahepatic cholangiocarcinoma (iCCA) using paired tumor and adjacent liver tissues from 262 patients. Integrated proteogenomic analyses prioritized genetic aberrations and revealed hallmarks of iCCA pathogenesis. Aflatoxin signature was associated with tumor initiation, proliferation, and immune suppression. Mutation-associated signaling profiles revealed that TP53 and KRAS co-mutations may contribute to iCCA metastasis via the integrin-FAK-SRC pathway. FGFR2 fusions activated the Rho GTPase pathway and could be a potential source of neoantigens. Proteomic profiling identified four patient subgroups (S1–S4) with subgroup-specific biomarkers. These proteomic subgroups had distinct features in prognosis, genetic alterations, microenvironment dysregulation, tumor microbiota composition, and potential therapeutics. SLC16A3 and HKDC1 were further identified as potential prognostic biomarkers associated with metabolic reprogramming of iCCA cells. This study provides a valuable resource for researchers and clinicians to further identify molecular pathogenesis and therapeutic opportunities in iCCA.
| Item Type: | Article |
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| Additional Information: | Data and code availability The data of WES, RNA-seq, proteome, and phosphoproteome generated in this study can be viewed in biosino NODE database (NODE database: OEP001105, https://www.biosino.org/node/project/detail/OEP001105). Sample annotation, processed, and normalized data files are provided as Table S1. The partial WES data of PDPCs from the previous cohort (Dong et al., 2018) can be accessed via the European Bioinformatics Institute (EBI EGA: EGAS00001002625). DGIdb (version 4.0.0) (Cotto et al., 2018) can be accessed via their portal at: https://www.dgidb.org/. GRCh37 genome assembly can be accessed via Genome Reference Consortium at https://www-ncbi-nlm-nih-gov.uea.idm.oclc.org/assembly/GCF_000001405.13. GRCh37 gencode v19 CTAT lib (version Oct012019) can be accessed via Broad institute website at https://data.broadinstitute.org/Trinity/CTAT_RESOURCE_LIB/__genome_libs_StarFv1.8/. SnpEff build-in hg19 reference (Cingolani et al., 2012) can be accessed via Pablo Cingolani website at https://pcingola.github.io/SnpEff/se_introduction/#databases. ANNOVAR filter-based annotation (Wang et al., 2010) can be found the ANNOVAR portal at https://annovar.openbioinformatics.org/en/latest/user-guide/download/. BSgenome.Hsapiens.UCSC.hg19 can be accessed via Bioconductor at https://bioconductor.org/packages/BSgenome.Hsapiens.UCSC.hg19/. Software and code used in this study are referenced in their corresponding STAR Methods sections and also the key resources table. |
| Uncontrolled Keywords: | fgfr2 fusion,intrahepatic cholangiocarcinoma,molecular subgroups,oncogenic drivers,prognostic biomarkers,proteogenomics,oncology,cancer research ,/dk/atira/pure/subjectarea/asjc/2700/2730 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 16 Mar 2026 16:30 |
| Last Modified: | 19 Mar 2026 09:33 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/102354 |
| DOI: | 10.1016/j.ccell.2021.12.006 |
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