Dual Regulatory Mechanisms of Expression and Mutation Involving Metabolism-Related Genes FDFT1 and UQCR5 during CLM
Colorectal cancer (CRC) is the third most common cancer worldwide, and liver metastasis presents a major cause of CRC-associated death. Extensive genomic analysis has provided valuable insight into the pathogenesis and progression of CRC; however, a comprehensive proteogenomic characterization of CR...
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| Format: | Article |
| Language: | English |
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Elsevier
2019-09-01
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| Series: | Molecular Therapy: Oncolytics |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2372770519300610 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Yu-Shui Ma Zhi-Jun Wu Hong-Wei Zhang Bo Cai Tao Huang Hui-Deng Long Hong Xu Yong-Zhong Zhao Yu-Zhen Yin Shao-Bo Xue Liu Li Cheng-Lin Liu Ru-Ting Xie Lin-Lin Tian Ji-Bin Liu Xu-Ming Wu Da Fu |
| spellingShingle |
Yu-Shui Ma Zhi-Jun Wu Hong-Wei Zhang Bo Cai Tao Huang Hui-Deng Long Hong Xu Yong-Zhong Zhao Yu-Zhen Yin Shao-Bo Xue Liu Li Cheng-Lin Liu Ru-Ting Xie Lin-Lin Tian Ji-Bin Liu Xu-Ming Wu Da Fu Dual Regulatory Mechanisms of Expression and Mutation Involving Metabolism-Related Genes FDFT1 and UQCR5 during CLM Molecular Therapy: Oncolytics |
| author_facet |
Yu-Shui Ma Zhi-Jun Wu Hong-Wei Zhang Bo Cai Tao Huang Hui-Deng Long Hong Xu Yong-Zhong Zhao Yu-Zhen Yin Shao-Bo Xue Liu Li Cheng-Lin Liu Ru-Ting Xie Lin-Lin Tian Ji-Bin Liu Xu-Ming Wu Da Fu |
| author_sort |
Yu-Shui Ma |
| title |
Dual Regulatory Mechanisms of Expression and Mutation Involving Metabolism-Related Genes FDFT1 and UQCR5 during CLM |
| title_short |
Dual Regulatory Mechanisms of Expression and Mutation Involving Metabolism-Related Genes FDFT1 and UQCR5 during CLM |
| title_full |
Dual Regulatory Mechanisms of Expression and Mutation Involving Metabolism-Related Genes FDFT1 and UQCR5 during CLM |
| title_fullStr |
Dual Regulatory Mechanisms of Expression and Mutation Involving Metabolism-Related Genes FDFT1 and UQCR5 during CLM |
| title_full_unstemmed |
Dual Regulatory Mechanisms of Expression and Mutation Involving Metabolism-Related Genes FDFT1 and UQCR5 during CLM |
| title_sort |
dual regulatory mechanisms of expression and mutation involving metabolism-related genes fdft1 and uqcr5 during clm |
| publisher |
Elsevier |
| series |
Molecular Therapy: Oncolytics |
| issn |
2372-7705 |
| publishDate |
2019-09-01 |
| description |
Colorectal cancer (CRC) is the third most common cancer worldwide, and liver metastasis presents a major cause of CRC-associated death. Extensive genomic analysis has provided valuable insight into the pathogenesis and progression of CRC; however, a comprehensive proteogenomic characterization of CRC liver metastasis (CLM) has yet to be reported. Here, we analyzed the proteomes of 44 paired normal colorectal tissues and CRC tissues with or without liver metastasis, as well as analyzed genomics of CRC characterized previously by The Cancer Genome Atlas (TCGA) to conduct integrated proteogenomic analyses. We identified a total of 2,170 significantly deregulated proteins associated with CLM, 14.88% of which were involved in metabolic pathways. The mutated peptide number was found to have potential prognosis value, and somatic variants revealed two metabolism-related genes UQCR5 and FDFT1 that frequently mutated only in the liver metastatic cohort and displayed dysregulated protein abundance with biological function and clinical significance in CLM. Proteogenomic characterization and integrative and comparative genomic analysis provides functional context and prognostic value to annotate genomic abnormalities and affords a new paradigm for understanding human colon and rectal cancer liver metastasis. Keywords: CRC, liver metastasis, proteomics, genomics, integrated analysis |
| url |
http://www.sciencedirect.com/science/article/pii/S2372770519300610 |
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doaj-a2c2cecbc6d44b9ca90680407fe2b7152020-11-24T21:27:06ZengElsevierMolecular Therapy: Oncolytics2372-77052019-09-0114172178Dual Regulatory Mechanisms of Expression and Mutation Involving Metabolism-Related Genes FDFT1 and UQCR5 during CLMYu-Shui Ma0Zhi-Jun Wu1Hong-Wei Zhang2Bo Cai3Tao Huang4Hui-Deng Long5Hong Xu6Yong-Zhong Zhao7Yu-Zhen Yin8Shao-Bo Xue9Liu Li10Cheng-Lin Liu11Ru-Ting Xie12Lin-Lin Tian13Ji-Bin Liu14Xu-Ming Wu15Da Fu16Department of Radiotherapy, Nantong Tumor Hospital, Nantong 226631, China; Central Laboratory for Medical Research, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China; Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, College of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, ChinaDepartment of Radiotherapy, Nantong Tumor Hospital, Nantong 226631, ChinaAnalytical Chemistry Platforms, Shanghai Institute for Advanced Immunochemical Studies, ShanghaiTech University, Shanghai 201210, ChinaDepartment of Chronic Diseases, Nantong Center for Disease Control and Prevention, Nantong 226007, ChinaInstitute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, ChinaCentral Laboratory for Medical Research, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaDepartment of Gastroenterology and Hepatology, Hangzhou Red Cross Hospital, Hangzhou 310003, ChinaDepartment of Medical Genetics, Southern Medical University, Guangzhou 510515, ChinaCentral Laboratory for Medical Research, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaCentral Laboratory for Medical Research, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaCentral Laboratory for Medical Research, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaSchool of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, ChinaCentral Laboratory for Medical Research, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaCentral Laboratory for Medical Research, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, ChinaCancer Institute, Nantong Tumor Hospital, Nantong 226631, China; Corresponding author: Ji-Bin Liu, Cancer Institute, Nantong Tumor Hospital, Nantong 226631, China.Department of Chronic Diseases, Nantong Center for Disease Control and Prevention, Nantong 226007, China; Corresponding author: Xu-Ming Wu, Department of Chronic Diseases, Nantong Center for Disease Control and Prevention, Nantong 226007, China.Central Laboratory for Medical Research, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China; Corresponding author: Da Fu, Central Laboratory for Medical Research, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China.Colorectal cancer (CRC) is the third most common cancer worldwide, and liver metastasis presents a major cause of CRC-associated death. Extensive genomic analysis has provided valuable insight into the pathogenesis and progression of CRC; however, a comprehensive proteogenomic characterization of CRC liver metastasis (CLM) has yet to be reported. Here, we analyzed the proteomes of 44 paired normal colorectal tissues and CRC tissues with or without liver metastasis, as well as analyzed genomics of CRC characterized previously by The Cancer Genome Atlas (TCGA) to conduct integrated proteogenomic analyses. We identified a total of 2,170 significantly deregulated proteins associated with CLM, 14.88% of which were involved in metabolic pathways. The mutated peptide number was found to have potential prognosis value, and somatic variants revealed two metabolism-related genes UQCR5 and FDFT1 that frequently mutated only in the liver metastatic cohort and displayed dysregulated protein abundance with biological function and clinical significance in CLM. Proteogenomic characterization and integrative and comparative genomic analysis provides functional context and prognostic value to annotate genomic abnormalities and affords a new paradigm for understanding human colon and rectal cancer liver metastasis. Keywords: CRC, liver metastasis, proteomics, genomics, integrated analysishttp://www.sciencedirect.com/science/article/pii/S2372770519300610 |