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pmid:36130456

Identification of a 5-gene-based signature to predict prognosis and correlate immunomodulators for rectal cancer.

Lin Yi · Ji Qiang · Peng Yichen · Yu Chunna · Zheng Yi · Kang Xun · Zheng Jianwei · Bai Rixing · Yan Wenmao · Wang Xiaomin · Li Parker · Li Wenbin

Translational oncology · 2022 doi:10.1016/j.tranon.2022.101529

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Experiment

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Data

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Analysis

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Identification of a 5-gene-based signature to predict prognosis and correlate immunomodulators for rectal cancer.
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10.1016/j.tranon.2022.101529
pmid
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Lin Yi
[1]
Ji Qiang
[2]
Peng Yichen
[3]
Yu Chunna
[4]
Zheng Yi
[5]
Kang Xun
[6]
Zheng Jianwei
[7]
Bai Rixing
[8]
Yan Wenmao
[9]
Wang Xiaomin
[10]
Li Parker
[11]
Li Wenbin
journal
Translational oncology
year
2022
abstract
BACKGROUND: Specific tumor markers have yet to be identified in rectal cancer. This study aims to identify a novel genetic signature in rectal cancer to provide clues for survival and immunotherapy. METHODS: DEGs were obtained from two GEO datasets of rectal cancer. By using data from TCGA and GSE133057, two cohorts of rectal cancer were applied to establish and evaluate the signature. A nomogram was constructed for training and validation. We integrated the risk-score with clinicopathological features and assessed its interplay with immune cells and molecules. Finally, our study performed functional annotations, gene-targeted miRNAs, and single-cell analysis. RESULTS: A total of 468 DEGs were identified, and a signature consisting of 5 genes (CLIC5, ENTPD8, PACSIN3, HGD, and GNG7) was selected to calculate the risk-score. The model exhibited high performance in time-dependent ROC and a nomogram. Further results showed that overall survival was significantly worse in the high-risk group. As an independent prognostic factor, the risk-score was associated with vascular invasion. There was a dramatic difference in nonregulatory CD4+ and CD8+ T cells between the high and low-risk groups, and the 5 genes were correlated with immune inhibitors. There was a considerable difference in autophagy, immune, cell cycle, infection, and apoptosis-associated terms and pathways in GO and KEGG. The functional states of differentiation, apoptosis, and quiescence were closely related to the 5-gene signature in single-cell analysis. CONCLUSION: Our results suggest that the signature could serve as a novel prognostic biomarker in rectal cancer, which might benefit decision-making regarding immunotherapy.
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Overall survival was plotted and calculated using the Kaplan–Meier method, and differences between groups were compared by the log-rank test. The Multivariate Cox analysis was carried out on the statistically significant variables in the univariate Cox regression.
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The 5-gene signature (CLIC5, ENTPD8, PACSIN3, HGD, and GNG7) stratified rectal cancer patients into high- and low-risk groups with significantly different overall survival in the TCGA cohort.
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It showed that overall survival is significantly low in the high-risk group (P = 0.0044, log-rank = 6.328).
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A signature consisting of 5 genes (CLIC5, ENTPD8, PACSIN3, HGD, and GNG7) was selected to construct a prognostic model in TCGA rectal cancer cohort and validated in the GSE133057 cohort.
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It showed that overall survival is significantly low in the high-risk group (P = 0.0044, log-rank = 6.328).
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The 5-gene signature (CLIC5, ENTPD8, PACSIN3, HGD, and GNG7) stratified rectal cancer patients into high- and low-risk groups with significantly different overall survival in the TCGA cohort.
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This study aims to identify a novel genetic signature in rectal cancer to provide clues for survival and immunotherapy.\nMETHODS: DEGs were obtained from two GEO datasets of rectal cancer. By using data from TCGA and GSE133057, two cohorts of rectal cancer were applied to establish and evaluate the signature. A nomogram was constructed for training and validation. We integrated the risk-score with clinicopathological features and assessed its interplay with immune cells and molecules. Finally, our study performed functional annotations, gene-targeted miRNAs, and single-cell analysis.\nRESULTS: A total of 468 DEGs were identified, and a signature consisting of 5 genes (CLIC5, ENTPD8, PACSIN3, HGD, and GNG7) was selected to calculate the risk-score. The model exhibited high performance in time-dependent ROC and a nomogram. Further results showed that overall survival was significantly worse in the high-risk group. 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