An immuno-score signature of tumor immune microenvironment predicts clinical outcomes in locally advanced rectal cancer

Zhengfa Xue; Shuxin Yang; Yun Luo; Ming He; Huimin Qiao; Wei Peng; Suxin Tong; Guini Hong; You Guo

doi:10.3389/fonc.2022.993726

An immuno-score signature of tumor immune microenvironment predicts clinical outcomes in locally advanced rectal cancer

Front Oncol. 2022 Sep 29:12:993726. doi: 10.3389/fonc.2022.993726. eCollection 2022.

Authors

Zhengfa Xue^{1

2}, Shuxin Yang³, Yun Luo¹, Ming He¹, Huimin Qiao¹, Wei Peng¹, Suxin Tong³, Guini Hong⁴, You Guo¹

Affiliations

¹ Medical Big Data and Bioinformatics Research Centre, First Affiliated Hospital of Gannan Medical University, Ganzhou, China.
² Department of Computer Science and Technology, School of Electronic and Information Engineering, Xi'an Jiao Tong University, Xi'an, China.
³ School of Information Engineering, Jiangxi University of Science and Technology, Ganzhou, China.
⁴ School of Medical Information Engineering, Gannan Medical University, Ganzhou, China.

Abstract

Background and purpose: Accumulating evidence indicates that neoadjuvant chemoradiotherapy(nCRT) success has an immune-associated constituent in locally advanced rectal cancer (LARC). The immune-associated configuration of the tumor microenvironment associated with responses to treatment was explored in LARC in this study.

Material and methods: A novel analytic framework was developed based on within-sample relative expression orderings for identifying tumor immune-associated gene pairs and identified an immuno-score signature from bulk transcriptome profiling analysis of 200 LARC patients. And sequencing and microarray analysis of gene expression was conducted to investigate the association between the signature and response to nCRT, immunotherapy, and cell function of CD4 and CD8. The results were validated using 111 pretreated samples from publicly available datasets in multiple aspects and survival analyses.

Results: The immuno-score signature of 18 immune-related gene pairs (referred to as IPS) was validated on bulk microarray and RNA-Seq data. According to the model's immune score, LARC patients were divided into high- and low-score groups. The patients with high-score were greater sensitivity to nCRT and immunotherapy, gaining a significantly improved prognosis. In addition, the immune-score gene pair signature was associated with type I anti-tumor T cell responses, positive regulators of T cell functions, and chromosomal instability while reflecting differences between CD8+ T cell subtypes.

Conclusion: The immuno-score signature underlines a key role of tumor immune components in nCRT response, and predicts the prognosis of LARC patients as well.

Keywords: immune gene pairs; immuno-score signature; locally advanced rectal cancer; neoadjuvant chemoradiotherapy; prognostic prediction.