121P - Single-cell sequencing reveals the role of Treg cells with high expression of BIRC3 in regulating the progression of colorectal cancer

Background

Colorectal cancer (CRC) is one of the most common malignancies, which has high morbidity and mortality rates globally. Recent studies have shown that tumor immune microenvironment (TIME) plays an important role in the development of CRC. Regulatory T cells (Tregs), a group of immunosuppressive cells, is significant in TIME. However, the role of Tregs in CRC is still controversial.

Methods

We used single-cell RNA sequencing (scRNA-seq) to profile the immune landscape of CRC, aiming to identify key subtype of Treg in the TIME that contribute to the development of CRC. The role of this key subtype of Treg in CRC prognosis was investigated by survival analyses of data from The Cancer Genome Atlas (TCGA) and multiple immunohistochemistry (mIHC) data of colorectal tumor samples collected from Zhongshan Hospital of Fudan University.

Results

Through scRNA-seq of tumor lesions of 13 patients with CRC, we found a new subtype of Treg, which was presented with high expression of baculoviral IAP repeat containing 3 (BIRC3). We confirmed its existence in colorectal cancer lesions by mIHC. Survival analysis of mIHC data from Zhongshan Hospital showed that Treg with high expression of BIRC3 was related with worse overall survival (OS) in CRC patients (P = 0.015). Survival analysis of TCGA database also reached a consistent result (P = 0.024). Multivariate analyses of both mIHC and TCGA data suggested that high expression of BIRC3 in Treg cells was an independent influencing factor for OS of CRC.

Conclusions

This study reveals that BIRC3 is expressed by Treg cells. High expression of BIRC3 in Treg cells indicates negative prognosis in CRC patients, which may provide a rationale for subsequent drug development and CRC management.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.