The global landscape of immune-derived lncRNA signature in colorectal cancer
Mengying Zhang,
Yifei Wu,
Jingyi Mou,
Yang Yao,
Pengbo Wen,
Xin Liu,
Shipeng Shang,
Xingxing Kang,
Jiaqi Tian,
Yan Liu,
Enhui Lv,
Liang Wang
Affiliations
Mengying Zhang
School of Medical Information and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu, China
Yifei Wu
School of Medical Information and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu, China
Jingyi Mou
Department of Clinical Medicine, School of 1st Clinical Medicine, Xuzhou Medical University, Xuzhou, China
Yang Yao
School of Medical Information and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu, China
Pengbo Wen
School of Medical Information and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu, China
Xin Liu
School of Medical Information and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu, China
Shipeng Shang
School of Basic Medicine, Qingdao University, Qingdao, China
Xingxing Kang
School of Medical Information and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu, China
Jiaqi Tian
School of Medical Information and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu, China
Yan Liu
School of Life Sciences, Xuzhou Medical University, Xuzhou, Jiangsu, China
Enhui Lv
School of Medical Information and Engineering, Xuzhou Medical University, Xuzhou, Jiangsu, China; Corresponding author.
Liang Wang
Laboratory Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China; Division of Microbiology and Immunology, School of Biomedical Sciences, The University of Western Australia, Crawley, Western Australia, Australia; Centre for Precision Health, School of Medical and Health Sciences, Edith Cowan University, Perth, Western Australia, Australia; School of Agriculture and Food Sustainability, University of Queensland, Brisbane, Queensland, Australia; Corresponding author. Laboratory Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, Guangdong Province, China
Background: Colorectal cancer (CRC) is a highly heterogeneous cancer. This heterogeneity has an impact on the efficacy of immunotherapy. Long noncoding RNAs (lncRNAs) have been found to play regulatory functions in cancer immunity. However, the global landscape of immune-derived lncRNA signatures has not yet been explored in colorectal cancer.Methods: In this study, we applied DESeq2 to identify differentially expressed lncRNAs in colon cancer. Next, we performed an integrative analysis to globally identify immune-driven lncRNA markers in CRC, including immune-associated pathways, tumor immunogenomic features, tumor-infiltrating immune cells, immune checkpoints, microsatellite instability (MSI) and tumor mutation burden (TMB).Results: We also identified dysregulated lncRNAs, such as LINC01354 and LINC02257, and their clinical relevance in CRC. Our findings revealed that the differentially expressed lncRNAs were closely associated with immune pathways. In addition, we found that RP11-354P11.3 and RP11-545G3.1 had the highest association with the immunogenomic signature. As a result, these signatures could serve as markers to assess immunogenomic activity in CRC. Among the immune cells, resting mast cells and M0 macrophages had the highest association with lncRNAs in CRC. The AC006129.2 gene was significantly associated with several immune checkpoints, for example, programmed cell death protein 1 (PD-1) and B and T lymphocyte attenuator (BTLA). Therefore, the AC006129.2 gene could be targeted to regulate the condition of immune cells or immune checkpoints to enhance the efficacy of immunotherapy in CRC patients. Finally, we identified 15 immune-related lncRNA-generated open reading frames (ORFs) corresponding to 15 cancer immune epitopes.Conclusion: In conclusion, we provided a genome-wide immune-driven lncRNA signature for CRC that might provide new insights into clinical applications and immunotherapy.
