Multi-omics analyses of human colorectal cancer revealed three mitochondrial genes potentially associated with poor outcomes of patients
Abstract Background The identification of novel functional biomarkers is essential for recognizing high-risk patients, predicting recurrence, and searching for appropriate treatment. However, no prognostic biomarker has been applied for colorectal cancer (CRC) in the clinic. Methods Integrated with...
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| Format: | Article |
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BMC
2021-06-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-021-02939-7 |
| _version_ | 1818914448662855680 |
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| author | Wei Zhang Liewen Lin Ligang Xia Wanxia Cai Weier Dai Chang Zou Lianghong Yin Donge Tang Yong Xu Yong Dai |
| author_facet | Wei Zhang Liewen Lin Ligang Xia Wanxia Cai Weier Dai Chang Zou Lianghong Yin Donge Tang Yong Xu Yong Dai |
| author_sort | Wei Zhang |
| collection | DOAJ |
| description | Abstract Background The identification of novel functional biomarkers is essential for recognizing high-risk patients, predicting recurrence, and searching for appropriate treatment. However, no prognostic biomarker has been applied for colorectal cancer (CRC) in the clinic. Methods Integrated with transcriptomic data from public databases, multi-omics examinations were conducted to search prognostic biomarkers for CRC. Moreover, the potential biological functions and regulatory mechanism of these predictive genes were also explored. Results In this study, we revealed that three mitochondrial genes were associated with the poor prognosis of CRC. Integrated analyses of transcriptome and proteome of CRC patients disclosed numerous down-regulated mitochondrial genes at both mRNA and protein levels, suggesting a vital role of mitochondria in carcinogenesis. Combined with the bioinformatics studies of transcriptomic datasets of 538 CRC patients, three mitochondrial prognostic genes were eventually selected out, including HIGD1A, SUCLG2, and SLC25A24. The expression of HIGD1A exhibited a significant reduction in two subtypes of adenoma and six subtypes of CRC, while the down-regulation of SUCLG2 and SLC25A24 showed more advantages in rectal mucinous adenocarcinoma. Moreover, we unveiled that these three genes had common expressions and might collaboratively participate in the synthesis of ribosomes. Our original multi-omics datasets, including DNA methylation, structural variants, chromatin accessibility, and phosphoproteome, further depicted the altered modifications on their potential transcriptional factors. Conclusions In summary, HIGD1A, SUCLG2, and SLC25A24 might serve as predictive biomarkers for CRC. The biological activities they involved in and their upstream regulators we uncovered would provide a functional context for the further-in-depth mechanism study. Graphic abstract |
| first_indexed | 2024-12-19T23:46:30Z |
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| id | doaj.art-4bc677e5e2d34c3182029ea343aaac2f |
| institution | Directory Open Access Journal |
| issn | 1479-5876 |
| language | English |
| last_indexed | 2024-12-19T23:46:30Z |
| publishDate | 2021-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Translational Medicine |
| spelling | doaj.art-4bc677e5e2d34c3182029ea343aaac2f2022-12-21T20:01:18ZengBMCJournal of Translational Medicine1479-58762021-06-0119111610.1186/s12967-021-02939-7Multi-omics analyses of human colorectal cancer revealed three mitochondrial genes potentially associated with poor outcomes of patientsWei Zhang0Liewen Lin1Ligang Xia2Wanxia Cai3Weier Dai4Chang Zou5Lianghong Yin6Donge Tang7Yong Xu8Yong Dai9Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital)Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital)Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital)Department of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital)College of Natural Science, University of Texas at AustinDepartment of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital)Department of Nephrology, Institute of Nephrology and Blood Purification, The First Affiliated Hospital of Jinan University, Jinan UniversityDepartment of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital)The First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s HospitalDepartment of Clinical Medical Research Center, Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital)Abstract Background The identification of novel functional biomarkers is essential for recognizing high-risk patients, predicting recurrence, and searching for appropriate treatment. However, no prognostic biomarker has been applied for colorectal cancer (CRC) in the clinic. Methods Integrated with transcriptomic data from public databases, multi-omics examinations were conducted to search prognostic biomarkers for CRC. Moreover, the potential biological functions and regulatory mechanism of these predictive genes were also explored. Results In this study, we revealed that three mitochondrial genes were associated with the poor prognosis of CRC. Integrated analyses of transcriptome and proteome of CRC patients disclosed numerous down-regulated mitochondrial genes at both mRNA and protein levels, suggesting a vital role of mitochondria in carcinogenesis. Combined with the bioinformatics studies of transcriptomic datasets of 538 CRC patients, three mitochondrial prognostic genes were eventually selected out, including HIGD1A, SUCLG2, and SLC25A24. The expression of HIGD1A exhibited a significant reduction in two subtypes of adenoma and six subtypes of CRC, while the down-regulation of SUCLG2 and SLC25A24 showed more advantages in rectal mucinous adenocarcinoma. Moreover, we unveiled that these three genes had common expressions and might collaboratively participate in the synthesis of ribosomes. Our original multi-omics datasets, including DNA methylation, structural variants, chromatin accessibility, and phosphoproteome, further depicted the altered modifications on their potential transcriptional factors. Conclusions In summary, HIGD1A, SUCLG2, and SLC25A24 might serve as predictive biomarkers for CRC. The biological activities they involved in and their upstream regulators we uncovered would provide a functional context for the further-in-depth mechanism study. Graphic abstracthttps://doi.org/10.1186/s12967-021-02939-7Prognostic biomarkersMitochondriaMulti-omics studyColorectal cancerRibosome |
| spellingShingle | Wei Zhang Liewen Lin Ligang Xia Wanxia Cai Weier Dai Chang Zou Lianghong Yin Donge Tang Yong Xu Yong Dai Multi-omics analyses of human colorectal cancer revealed three mitochondrial genes potentially associated with poor outcomes of patients Journal of Translational Medicine Prognostic biomarkers Mitochondria Multi-omics study Colorectal cancer Ribosome |
| title | Multi-omics analyses of human colorectal cancer revealed three mitochondrial genes potentially associated with poor outcomes of patients |
| title_full | Multi-omics analyses of human colorectal cancer revealed three mitochondrial genes potentially associated with poor outcomes of patients |
| title_fullStr | Multi-omics analyses of human colorectal cancer revealed three mitochondrial genes potentially associated with poor outcomes of patients |
| title_full_unstemmed | Multi-omics analyses of human colorectal cancer revealed three mitochondrial genes potentially associated with poor outcomes of patients |
| title_short | Multi-omics analyses of human colorectal cancer revealed three mitochondrial genes potentially associated with poor outcomes of patients |
| title_sort | multi omics analyses of human colorectal cancer revealed three mitochondrial genes potentially associated with poor outcomes of patients |
| topic | Prognostic biomarkers Mitochondria Multi-omics study Colorectal cancer Ribosome |
| url | https://doi.org/10.1186/s12967-021-02939-7 |
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