Clinical Significance and Inflammatory Landscape of aNovel Recurrence-Associated Immune Signature in Stage II/III Colorectal Cancer.

Zaoqu Liu,Jing Li,Taoyuan Lu,Long Liu,Chunguang Guo,Dechao Jiao,Kaihao Xu,Qin Dang,Libo Wang,Xinwei Han,Zhenqiang Sun

doi:10.3389/fimmu.2021.702594

Abstract

BackgroundA considerable number of patients with stage II/III colorectal cancer (CRC) will relapse within 5 years after surgery, which is a leading cause of death in early-stage CRC. The current TNM stage system is limited due to the heterogeneous clinical outcomes displayed in patients of same stage. Therefore, searching for a novel tool to identify patients at high recurrence-risk for improving post-operative individual management is an urgent need.MethodsUsing four independent public cohorts and qRT-PCR data from 66 tissues, we developed and validated a recurrence-associated immune signature (RAIS) based on global immune genes. The clinical and molecular features, tumor immune microenvironment landscape, and immune checkpoints profiles of RAIS were also investigated.ResultsIn five independent cohorts, this novel scoring system was proven to be an independent recurrent factor and displayed excellent discrimination and calibration in predicting the recurrence-risk at 1~5 years. Further analysis revealed that the high-risk group displayed high mutation rate of TP53, while the low-risk group had more abundance of activated CD4+/CD8+ T cells and high expression of PD-1/PD-L1.ConclusionsThe RAIS model is highly predictive of recurrence in patients with stage II/III CRC, which might serve as a powerful tool to further optimize decision-making in adjuvant chemotherapy and immunotherapy, as well as tailor surveillance protocol for individual patients.

Highlights

By 2020, colorectal cancer (CRC) has become the third most prevalent cancer and second leading cause of cancer-related mortality globally [1]
In this study, using four independent public cohorts with gene expression and recurrence-free survival (RFS) data, we developed and validated an individualized recurrence-associated immune signature (RAIS) for stage II/III CRC after surgical resection
The results showed that the area under the ROC (AUC) for predicting RFS at 1~5 years was 0.783, 0.841, 0.858, 0.859, and 0.951 in TCGA-CRC, 0.941, 0.922, 0.880, 0.878, and 0.877 in GSE143985, 0.892, 0.879, 0.840, 0.735, and 0.785 in GSE29621, and 0.962, 0.973, 0.961, 0.960, and 0.959 in GSE92921, respectively (Figure 4A)

Summary

Introduction

By 2020, colorectal cancer (CRC) has become the third most prevalent cancer and second leading cause of cancer-related mortality globally [1]. It is a conventional therapy for stage III and a subset of stage II CRC patients (e.g., T4, high grade) [3, 4]. The AJCC stage system alone is limited in stratifying these patients [10], searching for new ways to identify patients at high risk for recurrence who have urgent need for additional therapeutic schemes is imperative. A considerable number of patients with stage II/III colorectal cancer (CRC) will relapse within 5 years after surgery, which is a leading cause of death in early-stage CRC. Searching for a novel tool to identify patients at high recurrence-risk for improving post-operative individual management is an urgent need

Methods

Results

Conclusion