Derivation and Clinical Validation of a Redox-Driven Prognostic Signature for Colorectal Cancer.

Qin Dang,Zaoqu Liu,Guixian Wang,Weitang Yuan,Xinwei Han,Shengyun Hu,Zhuang Chen,Zhenqiang Sun,Lifeng Li,Lingfang Meng,Junhong Hu

doi:10.3389/fonc.2021.743703

Abstract

Colorectal cancer (CRC), a seriously threat that endangers public health, has a striking tendency to relapse and metastasize. Redox-related signaling pathways have recently been extensively studied in cancers. However, the study and potential role of redox in CRC remain unelucidated. We developed and validated a risk model for prognosis and recurrence prediction in CRC patients via identifying gene signatures driven by redox-related signaling pathways. The redox-driven prognostic signature (RDPS) was demonstrated to be an independent risk factor for patient survival (including OS and RFS) in four public cohorts and one clinical in-house cohort. Additionally, there was an intimate association between the risk score and tumor immune infiltration, with higher risk score accompanied with less immune cell infiltration. In this study, we used redox-related factors as an entry point, which may provide a broader perspective for prognosis prediction in CRC and have the potential to provide more promising evidence for immunotherapy.

Highlights

The incidence and mortality of colorectal cancer (CRC) are increasing worldwide [1, 2]
With “REDOX” as the keyword, we searched in the Molecular Signatures Database (MSigDB) [http://www.gseamsigdb.org/gsea/msigdb/index.jsp], and generated 11 relevant pathways
The modulation of redox-related pathways and targets has been shown to stimulate multiple signaling pathways to mediate the malignant phenotype of cancer, which involves cellspecific death [33], treatment sensitivity [24], proliferation, invasiveness, and angiogenesis [34]

Summary

Introduction

The incidence and mortality of colorectal cancer (CRC) are increasing worldwide [1, 2]. Limited by the choice of appropriate surgery timing and the operative range, and drug resistance to chemotherapy, malignant events such as adverse prognosis and metastasis in CRC patients are still intractable clinical problems [4, 5]. When treatment involving surgery, chemoradiotherapy, and targeted therapy fails, no alternative therapy modality is yet available. Immunotherapy has begun to take off in the treatment of tumors [6,7,8,9]. Our clinical practice shows that not all patients respond well to immunotherapy.

Methods

Results

Conclusion