Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma
Abstract Fibrolamellar Hepatocellular Carcinoma (FLC) is a rare liver cancer characterized by a fusion oncokinase of the genes DNAJB1 and PRKACA, the catalytic subunit of protein kinase A (PKA). A few FLC-like tumors have been reported showing other alterations involving PKA. To better understand FL...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-12-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55238-2 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841559305098100736 |
|---|---|
| author | David Requena Jack A. Medico Luis F. Soto-Ugaldi Mahsa Shirani James A. Saltsman Michael S. Torbenson Philip Coffino Sanford M. Simon |
| author_facet | David Requena Jack A. Medico Luis F. Soto-Ugaldi Mahsa Shirani James A. Saltsman Michael S. Torbenson Philip Coffino Sanford M. Simon |
| author_sort | David Requena |
| collection | DOAJ |
| description | Abstract Fibrolamellar Hepatocellular Carcinoma (FLC) is a rare liver cancer characterized by a fusion oncokinase of the genes DNAJB1 and PRKACA, the catalytic subunit of protein kinase A (PKA). A few FLC-like tumors have been reported showing other alterations involving PKA. To better understand FLC pathogenesis and the relationships among FLC, FLC-like, and other liver tumors, we performed a massive multi-omics analysis. RNA-seq data of 1412 liver tumors from FLC, hepatocellular carcinoma, hepatoblastoma and intrahepatic cholangiocarcinoma are analyzed, obtaining transcriptomic signatures unrestricted by experimental processing methods. These signatures reveal which dysregulations are unique to specific tumors and which are common to all liver cancers. Moreover, the transcriptomic FLC signature identifies a unifying phenotype for all FLC tumors regardless of how PKA was activated. We study this signature at multi-omics and single-cell levels in the first spatial transcriptomic characterization of FLC, identifying the contribution of tumor, normal, stromal, and infiltrating immune cells. Additionally, we study FLC metastases, finding small differences from the primary tumors. |
| format | Article |
| id | doaj-art-9fbc47a6bf6f4c708c96b3df4073395f |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-9fbc47a6bf6f4c708c96b3df4073395f2025-01-05T12:36:45ZengNature PortfolioNature Communications2041-17232024-12-0115112010.1038/s41467-024-55238-2Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinomaDavid Requena0Jack A. Medico1Luis F. Soto-Ugaldi2Mahsa Shirani3James A. Saltsman4Michael S. Torbenson5Philip Coffino6Sanford M. Simon7Laboratory of Cellular Biophysics, The Rockefeller UniversityLaboratory of Cellular Biophysics, The Rockefeller UniversityLaboratory of Cellular Biophysics, The Rockefeller UniversityLaboratory of Cellular Biophysics, The Rockefeller UniversityLaboratory of Cellular Biophysics, The Rockefeller UniversityDivision of Anatomic Pathology, Mayo ClinicLaboratory of Cellular Biophysics, The Rockefeller UniversityLaboratory of Cellular Biophysics, The Rockefeller UniversityAbstract Fibrolamellar Hepatocellular Carcinoma (FLC) is a rare liver cancer characterized by a fusion oncokinase of the genes DNAJB1 and PRKACA, the catalytic subunit of protein kinase A (PKA). A few FLC-like tumors have been reported showing other alterations involving PKA. To better understand FLC pathogenesis and the relationships among FLC, FLC-like, and other liver tumors, we performed a massive multi-omics analysis. RNA-seq data of 1412 liver tumors from FLC, hepatocellular carcinoma, hepatoblastoma and intrahepatic cholangiocarcinoma are analyzed, obtaining transcriptomic signatures unrestricted by experimental processing methods. These signatures reveal which dysregulations are unique to specific tumors and which are common to all liver cancers. Moreover, the transcriptomic FLC signature identifies a unifying phenotype for all FLC tumors regardless of how PKA was activated. We study this signature at multi-omics and single-cell levels in the first spatial transcriptomic characterization of FLC, identifying the contribution of tumor, normal, stromal, and infiltrating immune cells. Additionally, we study FLC metastases, finding small differences from the primary tumors.https://doi.org/10.1038/s41467-024-55238-2 |
| spellingShingle | David Requena Jack A. Medico Luis F. Soto-Ugaldi Mahsa Shirani James A. Saltsman Michael S. Torbenson Philip Coffino Sanford M. Simon Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma Nature Communications |
| title | Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma |
| title_full | Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma |
| title_fullStr | Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma |
| title_full_unstemmed | Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma |
| title_short | Liver cancer multiomics reveals diverse protein kinase A disruptions convergently produce fibrolamellar hepatocellular carcinoma |
| title_sort | liver cancer multiomics reveals diverse protein kinase a disruptions convergently produce fibrolamellar hepatocellular carcinoma |
| url | https://doi.org/10.1038/s41467-024-55238-2 |
| work_keys_str_mv | AT davidrequena livercancermultiomicsrevealsdiverseproteinkinaseadisruptionsconvergentlyproducefibrolamellarhepatocellularcarcinoma AT jackamedico livercancermultiomicsrevealsdiverseproteinkinaseadisruptionsconvergentlyproducefibrolamellarhepatocellularcarcinoma AT luisfsotougaldi livercancermultiomicsrevealsdiverseproteinkinaseadisruptionsconvergentlyproducefibrolamellarhepatocellularcarcinoma AT mahsashirani livercancermultiomicsrevealsdiverseproteinkinaseadisruptionsconvergentlyproducefibrolamellarhepatocellularcarcinoma AT jamesasaltsman livercancermultiomicsrevealsdiverseproteinkinaseadisruptionsconvergentlyproducefibrolamellarhepatocellularcarcinoma AT michaelstorbenson livercancermultiomicsrevealsdiverseproteinkinaseadisruptionsconvergentlyproducefibrolamellarhepatocellularcarcinoma AT philipcoffino livercancermultiomicsrevealsdiverseproteinkinaseadisruptionsconvergentlyproducefibrolamellarhepatocellularcarcinoma AT sanfordmsimon livercancermultiomicsrevealsdiverseproteinkinaseadisruptionsconvergentlyproducefibrolamellarhepatocellularcarcinoma |