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Cancer Immunology, Immunotherapy
Published in: Cancer Immunology, Immunotherapy 4/2024

Open Access 01-04-2024 | Colorectal Cancer | Research

Construction of an immune predictive model and identification of TRIP6 as a prognostic marker and therapeutic target of CRC by integration of single-cell and bulk RNA-seq data

Authors: Wenjun Liu, Xitu Luo, Zilang Zhang, Yepeng Chen, Yongliang Dai, Jianzhong Deng, Chengyu Yang, Hao Liu

Published in: Cancer Immunology, Immunotherapy | Issue 4/2024

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Abstract

Background

Investigations elucidating the complex immunological mechanisms involved in colorectal cancer (CRC) and accurately predicting patient outcomes via bulk RNA-Seq analysis have been notably limited. This study aimed to identify the immune status of CRC patients, construct a prognostic model, and identify prognostic signatures via bulk RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq).

Methods

The scRNA-seq data of CRC were downloaded from Gene Expression Omnibus (GEO). The UCSC Xena database was used to obtain bulk RNA-seq data. Differentially expressed gene (DEG), functional enrichment, and random forest analyses were conducted in order to identify core genes associated with colorectal cancer (CRC) that were relevant to prognosis. A molecular immune prediction model was developed using logistic regression after screening features using the least absolute shrinkage and selection operator (LASSO). The differences in immune cell infiltration, mutation, chemotherapeutic drug sensitivity, cellular senescence, and communication between patients who were at high and low risk of CRC according to the predictive model were investigated. The prognostic genes that were closely associated with CRC were identified by random survival forest (RSF) analysis. The expression levels and clinical significance of the hub genes were analyzed in vitro. The LoVo cell line was employed to ascertain the biological role of thyroid hormone receptor-interacting protein 6 (TRIP6).

Results

A total of seven main cell subtypes were identified by scRNA-seq analysis. A molecular immune predictive model was constructed based on the risk scores. The risk score was significantly associated with OS, stage, mutation burden, immune cell infiltration, response to immunotherapy, key pathways, and cell–cell communication. The functions of the six hub genes were determined and further utilized to establish a regulatory network. Our findings unequivocally confirmed that TRIP6 upregulation was verified in the CRC samples. After knocking down TRIP6, cell proliferation, migration, and invasion of LoVo cells were inhibited, and apoptosis was promoted.

Conclusions

The molecular predictive model reliably distinguished the immune status of CRC patients. We further revealed that TRIP6 may act as an oncogene in CRC, making it a promising candidate for targeted therapy and as a prognostic marker for CRC.
Appendix
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Metadata
Title
Construction of an immune predictive model and identification of TRIP6 as a prognostic marker and therapeutic target of CRC by integration of single-cell and bulk RNA-seq data
Authors
Wenjun Liu
Xitu Luo
Zilang Zhang
Yepeng Chen
Yongliang Dai
Jianzhong Deng
Chengyu Yang
Hao Liu
Publication date
01-04-2024
Publisher
Springer Berlin Heidelberg
Published in
Cancer Immunology, Immunotherapy / Issue 4/2024
Print ISSN: 0340-7004
Electronic ISSN: 1432-0851
DOI
https://doi.org/10.1007/s00262-024-03658-w

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