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

doi:10.1016/j.tranon.2022.101529

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

Transl Oncol. 2022 Dec:26:101529. doi: 10.1016/j.tranon.2022.101529. Epub 2022 Sep 18.

Authors

Lin Yi¹, Ji Qiang², Peng Yichen³, Yu Chunna³, Zheng Yi², Kang Xun³, Zheng Jianwei⁴, Bai Rixing⁴, Yan Wenmao⁴, Wang Xiaomin⁵, Li Parker⁶, Li Wenbin⁷

Affiliations

¹ Department of General Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Neuro-oncology, Cancer Center, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
² Department of Neuro-oncology, Cancer Center, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China.
³ Department of Neuro-oncology, Cancer Center, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁴ Department of General Surgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
⁵ Department of Neuro-oncology, Cancer Center, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China; Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, China. Electronic address: wangxiaomin@ihcams.ac.cn.
⁶ Clinical Medicine, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
⁷ Department of Neuro-oncology, Cancer Center, China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, China. Electronic address: liwenbin@ccmu.edu.cn.

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.

Keywords: Bioinformatics; Biomarker; Differentially expressed genes; Prognosis; Rectal cancer.