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. 2021 Nov 8:2021:4682589.
doi: 10.1155/2021/4682589. eCollection 2021.

Establishing and Validating an Aging-Related Prognostic Four-Gene Signature in Colon Adenocarcinoma

Lian Zheng  1 , Yang Yang  2 , Xiaorong Cui  2
Affiliations

Establishing and Validating an Aging-Related Prognostic Four-Gene Signature in Colon Adenocarcinoma

Lian Zheng et al. Biomed Res Int. .

Retraction in

Abstract

Background: Aging is a process that biological changes accumulate with time and lead to increasing susceptibility to diseases like cancer. This study is aimed at establishing an aging-related prognostic signature in colon adenocarcinoma (COAD).

Methods: The transcriptome data and clinical variables of COAD patients were downloaded from TCGA database. The genes in GOBP_AGING gene set was used for prognostic evaluation by the univariate and multivariate Cox regression analyses. The model was presented by a nomogram and assessed by the Kaplan-Meier curves and calibration curves. The drug response and gene mutation were also performed to implicate the clinical significance. The GO and KEGG analyses were employed to unravel the potential functional mechanism.

Results: The Gene Set Enrichment Analysis result indicates that GOBP_AGING pathway is significantly enriched in COAD samples. Four aging-related genes are finally used to construct the aging-related prognostic signature: FOXM1, PTH1R, KL, and CGAS. The COAD patients with high risk score have much shorter overall survival in both train cohort and test cohort. The nomogram is then assembled to predict 1-year, 3-year, and 5-year survival. Patients with high risk score have elevated infiltrating B cell naïve and attenuated cisplatin sensitivity. The mutation landscape shows that the TTN, FAT4, ZFHX4, APC, and OBSCN gene mutation are different between high risk score patients and low risk score patients. The differentially expressed genes between patients with high score and low score are enriched in B cell receptor signaling pathway.

Conclusion: We constructed an aging-related signature in COAD patients, which can predict oncological outcome and optimize therapeutic strategy.

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Conflict of interest statement

The authors declare that there is no conflict of interest.

Figures

Figure 1
Figure 1
Evaluation of aging genes in colon cancer. (a) Gene Set Enrichment Analysis for colon cancer using GOBP_AGING gene set. (b) Volcano plot for aging genes in colon cancer. (c) Venn plot for differentially expressed aging genes and prognostic genes. (d) Heatmap for aging genes with prognostic value.
Figure 2
Figure 2
Identification of aging-related prognostic signature. (a) Univariate Cox analysis for significant aging genes. The distribution of risk scores and survival status of colon cancer patients with different risk scores in (b) train cohort and (d) test cohort. The survival curves for patients with high risk score and low risk score in (c) train cohort and (e) test cohort.
Figure 3
Figure 3
Establishment of an aging-related prognostic model to predict overall survival in colon cancer patients. (a) The nomogram presenting the aging-related prognostic model. The calibration curves in train cohort, test cohort, and all patients.
Figure 4
Figure 4
The differentially infiltrating immune cells in colon cancer patients with high risk score and low risk score. (a) Profile of infiltrating immune cells in colon cancer patients. Differentially infiltrating (a) B cell naïve, (c) B cell memory, (d) macrophage M0, (e) mast cells activated, (f) T cell CD8, and (g) T cell regulatory (Tregs) between high-risk patients and low-risk patients.
Figure 5
Figure 5
The sensitivity of high-risk patients and low-risk patients to (a) cisplatin, (b) cyclopamine, and (c) paclitaxel. Mutation frequency in (d) high-risk patients and (e) low-risk patients.
Figure 6
Figure 6
(a) Differentially expressed genes between high-risk patients and low-risk patients. (b) GO analysis and (c) KEGG analysis for differentially expressed genes.
Figure 7
Figure 7
The protein-protein interaction network for differentially expressed genes.
See this image and copyright information in PMC

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