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Updated: Jun 18, 2025
Isolation of Nuclei from Flash-Frozen Liver Tissue for Single-Cell Multiomics
Published on: December 9, 2022
Transcriptomic profiling of intermediate cell carcinoma of the liver
Byungchan Jang1,2, So Mee Kwon1, Jang Hyun Kim1,2
1Department of Physiology, Ajou University School of Medicine, Suwon, Republic of Korea.
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.
