Frontiers in Oncology (Jun 2021)
Regulatory Network Analysis of Mutated Genes Based on Multi-Omics Data Reveals the Exclusive Features in Tumor Immune Microenvironment Between Left-Sided and Right-Sided Colon Cancer
- Tianfei Yi,
- Tianfei Yi,
- Tianfei Yi,
- Yuwei Zhang,
- Yuwei Zhang,
- Derry Minyao Ng,
- Derry Minyao Ng,
- Yang Xi,
- Meng Ye,
- Lvjun Cen,
- Jianjiong Li,
- Jianjiong Li,
- Jianjiong Li,
- Xiaoxiang Fan,
- Xiaoxiang Fan,
- Xiaoxiang Fan,
- Yanguo Li,
- Shiyun Hu,
- Shiyun Hu,
- Shiyun Hu,
- Hao Rong,
- Hao Rong,
- Hao Rong,
- Yangyang Xie,
- Yangyang Xie,
- Yangyang Xie,
- Guofang Zhao,
- Guofang Zhao,
- Leyi Chen,
- Leyi Chen,
- Chen Chen,
- Chen Chen,
- Shujing Ni,
- Shujing Ni,
- Jiaying Mi,
- Jiaying Mi,
- Xiaoyu Dai,
- Xiaoyu Dai,
- Xiaoyu Dai,
- Qi Liao,
- Qi Liao,
- Qi Liao
Affiliations
- Tianfei Yi
- The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
- Tianfei Yi
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Tianfei Yi
- Department of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Yuwei Zhang
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Yuwei Zhang
- Department of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Derry Minyao Ng
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Derry Minyao Ng
- Department of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Yang Xi
- Department of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Meng Ye
- The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
- Lvjun Cen
- The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
- Jianjiong Li
- Hua Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Jianjiong Li
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Jianjiong Li
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China
- Xiaoxiang Fan
- Hua Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Xiaoxiang Fan
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Xiaoxiang Fan
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China
- Yanguo Li
- Institute of Drug Discovery Technology, Ningbo University, Ningbo, China
- Shiyun Hu
- The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
- Shiyun Hu
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Shiyun Hu
- Department of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Hao Rong
- The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
- Hao Rong
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Hao Rong
- Department of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Yangyang Xie
- Hua Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Yangyang Xie
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Yangyang Xie
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China
- Guofang Zhao
- Hua Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Guofang Zhao
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Leyi Chen
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Leyi Chen
- Department of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Chen Chen
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Chen Chen
- Department of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Shujing Ni
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Shujing Ni
- Department of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Jiaying Mi
- Hua Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Jiaying Mi
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Xiaoyu Dai
- Hua Mei Hospital, University of Chinese Academy of Sciences, Ningbo, China
- Xiaoyu Dai
- Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences, Ningbo, China
- Xiaoyu Dai
- Key Laboratory of Diagnosis and Treatment of Digestive System Tumors of Zhejiang Province, Ningbo, China
- Qi Liao
- The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
- Qi Liao
- Department of Preventative Medicine, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- Qi Liao
- Department of Biochemistry and Molecular Biology, Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, China
- DOI
- https://doi.org/10.3389/fonc.2021.685515
- Journal volume & issue
-
Vol. 11
Abstract
Left-sided colon cancer (LCC) and right-sided colon cancer (RCC) have distinct characteristics in tumor immune microenvironment (TIME). Although existing studies have shown a strong association between gene mutations and TIME, whether the regulatory mechanisms between gene mutations and TIME are different between RCC and LCC is still unclear. In this study, we showed the fractions of CD8+ T cells were higher while those of regulatory T cells were lower in RCC. Besides, a stronger association between gene mutations and TIME was observed in RCC. Specifically, using multi-omics data, we demonstrated the mutations of most top mutated genes (TMGs) including BRAF, PCLO, MUC16, LRP2, ANK3, KMT2D, RYR2 made great contributions to elevated fraction of immune cells by up-regulating immune-related genes directly or indirectly through miRNA and DNA methylation, whereas the effects of APC, TP53 and KRAS mutations on TIME were reversed in RCC. Remarkably, we found the expression levels of several immune checkpoint molecules such as PD-1 and LAG3 were correlated with corresponding DNA methylation levels, which were associated with the mutations of TMGs in RCC. In contrast, the associations between gene mutations and TIME were less significant in LCC. Besides, survival analyses showed APC mutation had adverse impact on immunotherapy while patients with BRAF mutation were more suitable for immunotherapy in colon cancer. We hope that our results will provide a deeper insight into the sophisticated mechanism underlying the regulation between mutations and TIME, and thus boost the discovery of differential immunotherapeutic strategies for RCC and LCC.
Keywords
- left-sided colon cancer (LCC)
- right-sided colon cancer (RCC)
- tumor immune microenvironment (TIME)
- gene mutation
- multi-omics
- immunotherapy
