Transcriptomic profiling of intermediate cell carcinoma of the liver.
Hepatol Commun
; 8(8)2024 08 01.
Article
em En
| MEDLINE
| ID: mdl-39101773
ABSTRACT
BACKGROUND:
Intermediate cell carcinoma (Int-CA) is a rare and enigmatic primary liver cancer characterized by uniform tumor cells exhibiting mixed features of both HCC and intrahepatic cholangiocarcinoma. Despite the unique pathological features of int-CA, its molecular characteristics remain unclear yet.METHODS:
RNA sequencing and whole genome sequencing profiling were performed on int-CA tumors and compared with those of HCC and intrahepatic cholangiocarcinoma.RESULTS:
Int-CAs unveiled a distinct and intermediate transcriptomic feature that is strikingly different from both HCC and intrahepatic cholangiocarcinoma. The marked abundance of splicing events leading to intron retention emerged as a signature feature of int-CA, along with a prominent expression of Notch signaling. Further exploration revealed that METTL16 was suppressed within int-CA, showing a DNA copy number-dependent transcriptional deregulation. Notably, experimental investigations confirmed that METTL16 suppression facilitated invasive tumor characteristics through the activation of the Notch signaling cascade.CONCLUSIONS:
Our results provide a molecular landscape of int-CA featured by METTL16 suppression and frequent intron retention events, which may play pivotal roles in the acquisition of the aggressive phenotype of Int-CA.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Colangiocarcinoma
/
Carcinoma Hepatocelular
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Perfilação da Expressão Gênica
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Neoplasias Hepáticas
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article