J Cancer 2020; 11(11):3124-3143. doi:10.7150/jca.38057 This issue

Research Paper

Peroxiredoxins and Immune Infiltrations in Colon Adenocarcinoma: Their Negative Correlations and Clinical Significances, an In Silico Analysis

Xiuzhi Zhang1,2,3, Fenglan Gao1, Ningning Li1, Jinzhong Zhang2✉, Liping Dai3✉, Hongmei Yang1,2✉

1. Department of Pathology, Henan Medical College, Zhengzhou, Henan Province, China
2. Medical Laboratory Center, Henan Medical College, Zhengzhou, Henan Province, China
3. Henan Institute of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province, China

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Zhang X, Gao F, Li N, Zhang J, Dai L, Yang H. Peroxiredoxins and Immune Infiltrations in Colon Adenocarcinoma: Their Negative Correlations and Clinical Significances, an In Silico Analysis. J Cancer 2020; 11(11):3124-3143. doi:10.7150/jca.38057. Available from https://www.jcancer.org/v11p3124.htm

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Background: Peroxiredoxins (PRDXs) were reported to be associated with inflammation response in previous studies. In colon adenocarcinoma (COAD), however, their correlations and clinical significance were unclear.

Methods: The RNA-seq data of 452 COAD patients with clinical information was downloaded from The Cancer Genome Atlas (TCGA) and transcripts per million (TPM) normalized. Comparisons of relative expressions of PRDXs between COAD tumor and normal controls were applied. PRDXs dy-regulations in COAD were validated via Oncomine, Human Protein Atlas (HPA) and Gene Expression Omnibus (GEO) repository. Through Tumor Immune Estimation Resource (TIMER), the immune estimation of TCGA-COAD patients was downloaded and the dy-regulated PRDXs were analyzed for their correlations with immune infiltrations in COAD. The TCGA-COAD patients were divided into younger group (age≤65 years) and older group (age>65 years) to investigate the prognostic roles of age, TNM stage, dy-regulated PRDXs and the immune infiltrations in different age groups through Kaplan-Meier survival and Cox regression analyses.

Results: Three of the PRDX members showed their expressional differences both at protein and mRNA level. PRDX2 was consistently up-regulated while PRDX6 down-regulated in COAD. PRDX1 was overexpressed (mRNA) while nuclear absent (protein) in the tumor tissues. PRDX1 overexpression and PRDX6 under-expression were also shown in the stem-like colonospheres from colon cancer cells. Via TIMER, PRDX1, PRDX2, and PRDX6 were found to be negatively correlated with the immune infiltrations in COAD. Both in the younger and older patients, TNM stage had prognostic effects on their overall survival (OS) and recurrence-free survival (RFS). CD4+ T cell had independent unfavorable effects on OS of the younger patients while age had similar effects on RFS of the older ones. CD8+ T cell was independently prognostic for RFS in the two groups.

Conclusions: Late diagnosis indicated poor prognosis in COAD and dy-regulated PRDXs w might be new markers for its early diagnosis. Age was prognostic and should be considered in the treatments of the older patients. Dy-regulated PRDXs were negatively correlated with immune infiltration levels. CD4+ T cell and CD8+ T cell infiltrations were prognostic in COAD and their potential as immune targets needed further investigation.

Keywords: peroxiredoxins (PRDXs), immune infiltration, colon adenocarcinoma (COAD), diagnosis, prognosis