Multi-Platform-Based Analysis Characterizes Molecular Alterations of the Nucleus in Human Colorectal Cancer

Wei Zhang; Minmin Wu; Xucan Gao; Chiyu Ma; Huixuan Xu; Liewen Lin; Jingquan He; Wanxia Cai; Yafang Zhong; Donge Tang; Min Tang; Yong Dai

doi:10.3389/fcell.2022.796703

Multi-Platform-Based Analysis Characterizes Molecular Alterations of the Nucleus in Human Colorectal Cancer

Front Cell Dev Biol. 2022 Feb 21:10:796703. doi: 10.3389/fcell.2022.796703. eCollection 2022.

Authors

Wei Zhang^{1

2}, Minmin Wu³, Xucan Gao¹, Chiyu Ma¹, Huixuan Xu¹, Liewen Lin¹, Jingquan He¹, Wanxia Cai¹, Yafang Zhong¹, Donge Tang¹, Min Tang³, Yong Dai¹

Affiliations

¹ Department of Clinical Medical Research Center, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, China.
² South China Hospital, Health Science Center, Shenzhen University, Shenzhen, China.
³ Key Laboratory of Clinical Laboratory Diagnostics of Ministry of Education, Chongqing Medical University, Chongqing, China.

Abstract

Background: The disturbed molecular alterations of nucleus may promote the development of colorectal cancer (CRC). A multi-platform-based analysis of nucleus of CRC patients helps us to better understand the underlying mechanism of CRC and screen out the potential drug targets for clinical treatment. However, such studies on nucleus in human CRC are still lacking. Methods: We collected the cancerous and para-cancerous tissues from eight CRC patients and performed a multiplex analysis of the molecular changes of the nucleus, including structural variations (SVs), DNA methylation, chromatin accessibility, proteome and phosphorproteome. Results: In our study, we revealed a significant molecular change of nucleus of CRC patients using our original proteomic and phosphorylomic datasets. Subsequently, we characterized the molecular alterations of nucleus of CRC patients at multiple dimensionalities, including DNA, mRNA, protein and epigenetic modification. Next, we found that the great molecular changes of nucleus might affect the biological processes named endocytosis and ubiquitin-mediated proteolysis. Besides, we identified DYNC1LI2 and TPR as the potentially hub proteins within the network of nuclear genes in CRC cells. Furthermore, we identified 1905 CRC-specific SVs, and proclaimed 17 CRC-specific SVs were probably associated with the disturbance of immune microenvironment of CRC patients. We also revealed that the SVs of CXCL5, CXCL10 and CXCL11 might be the core SVs among all the immune-relevant SVs. Finally, we identified seven genes as the upstream transcriptional factors potentially regulating the expression of nuclear genes, such as YY1 and JUN, using a multi-omics approach. Conclusion: Here, we characterized the molecular changes of nucleus of CRC patients, disclosed the potentially core nuclear genes within the network, and identified the probable upstream regulator of nucleus. The findings of this study are helpful to understand the pathogenic molecular changes of nucleus in CRC patients and provide a functional context for drug development in future.

Keywords: colorectal cancer; immune microenvironment; multiomics; nucleus; structural variations.