The application of single-cell transcriptome technology by Cui Jie team at eBioMedicine highlighted the potential function of human endogenous retroviruses in gallbladder cancer

On October 28, Lancet's international journal eBioMedicine published online the latest research results of Cui Jie's research group at the Shanghai Pasteur Institute of the Chinese Academy of Sciences entitled Single-cell RNA sequencing highlights the functional role of human endogenous retroviruses in gallbladder cancer
。

Gallbladder cancer (GBC) is the most common biliary tract cancer and is characterized by difficult early diagnosis, rapid progression, and a poor overall prognosis, requiring continued search for early diagnostic markers and the development of new treatment strategies
.
Human endogenous retroviruses (HERVs) are viral "fossils" that ancient retroviruses integrate into the genomes of human ancestors and are inherited through Mendelian laws of heredity, accounting for about 8%
of the human genome.
HERV is specifically activated and associated with cancer development in a variety of cancers, and in recent years, exploring the potential of HERV as a diagnostic marker and therapeutic target has gradually attracted worldwide attention
.
At present, the association between HERV and GBC is unclear, and single-cell data lack HERV-class markers, so Cui Jie's research group, together with Oriental Hepatobiliary Hospital and Dongfang Hospital, jointly explored the single-cell transcription mode of HERV in GBC and its potential impact
on cell function.

Legend: Expression patterns of HERV in gallbladder cancer tumor tissue and paracancerous tissue

This study used single-cell transcriptome sequencing technology to reveal the cellular composition of the tumor microenvironment of gallbladder cancer, mapped the transcription of HERV in various cell types, and confirmed the abnormal activation of HERV in gallbladder cancer and the difference
in cell function of cells with cell type specificity and different HERV family associations.
The study experimentally confirmed that HERV can function as an enhancer, thereby changing the expression pattern
of neighboring genes of HERV.
Based on the transcriptional characteristics of HERV, the study proposed that HERVH (HHERV family class H) can be used as a potential early diagnostic biomarker for GBC and that the HERVH-derived immune checkpoint HHLA2 is promising as an immunotherapy target for GBC
.
These findings highlight the important role of HERV in shaping the tumor microenvironment, providing new medical insights
for better understanding the occurrence and progression of gallbladder cancer.

Dr.
Wang Jinghan of Dongfang Hospital and Ren Meng, scientific research assistant of Shanghai Pasteur Institute, are the co-first authors of this paper, and Cui Jie, researcher of Shanghai Pasteur Institute and Professor Jiang Xiaoqing of Oriental Hepatobiliary Surgery Hospital, are the co-corresponding authors
of this paper.

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