Single-cell transcriptomics and Mendelian randomization reveal LUCAT1’s role in right-sided colorectal cancer risk
Background: Colorectal cancer (CRC) is a malignancy with high incidence and mortality rates globally, categorized into left-sided and right-sided CRC, each exhibiting significant differences in molecular characteristics, clinical manifestations, and prognosis.Methods: This study employed single-cell...
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| Format: | Article |
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Frontiers Media S.A.
2024-04-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2024.1357704/full |
| _version_ | 1797198714756923392 |
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| author | Zhihao Shang Zhihao Shang Songyang Xi Songyang Xi Songyang Xi Yueyang Lai Yueyang Lai Haibo Cheng Haibo Cheng |
| author_facet | Zhihao Shang Zhihao Shang Songyang Xi Songyang Xi Songyang Xi Yueyang Lai Yueyang Lai Haibo Cheng Haibo Cheng |
| author_sort | Zhihao Shang |
| collection | DOAJ |
| description | Background: Colorectal cancer (CRC) is a malignancy with high incidence and mortality rates globally, categorized into left-sided and right-sided CRC, each exhibiting significant differences in molecular characteristics, clinical manifestations, and prognosis.Methods: This study employed single-cell transcriptomic data and various bioinformatics approaches, such as two-sample Mendelian randomization, reverse Mendelian randomization, colocalization analysis, directed filtering, pseudotime analysis, and intercellular communication analysis. It analyzed cellular-level disparities between left-sided and right-sided CRC, identifying distinct subpopulations with characteristic variations. For these cells, two-sample Mendelian randomization was utilized to explore gene-to-one-sided CRC causality.Results: LUCAT1 was enriched in high-abundance monocyte subpopulations in right-sided CRC and demonstrated potential risk factor status through Mendelian randomization analysis. The specific single-nucleotide polymorphism (SNP) rs10774624 was associated with an increased risk of CRC. Moreover, metabolic pathway analysis revealed that LUCAT1+ monocytes exhibit lower communication activity in the tumor microenvironment and heightened activity in metabolic functions like glycosaminoglycan degradation. Its biological functions are related to the positive regulation of interleukin-6 production and NF-kappa B signaling, among others.Conclusion: This study confirmed a potential causal relationship between LUCAT1 and right-sided CRC risk through Mendelian randomization analysis. These findings provide novel insights into the pathogenesis of right-sided CRC and may aid in developing early detection and treatment strategies for right-sided CRC. |
| first_indexed | 2024-04-24T07:04:15Z |
| format | Article |
| id | doaj.art-5fa87fc43e6c4ba683cac033089af049 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-24T07:04:15Z |
| publishDate | 2024-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-5fa87fc43e6c4ba683cac033089af0492024-04-22T04:51:15ZengFrontiers Media S.A.Frontiers in Genetics1664-80212024-04-011510.3389/fgene.2024.13577041357704Single-cell transcriptomics and Mendelian randomization reveal LUCAT1’s role in right-sided colorectal cancer riskZhihao Shang0Zhihao Shang1Songyang Xi2Songyang Xi3Songyang Xi4Yueyang Lai5Yueyang Lai6Haibo Cheng7Haibo Cheng8Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, ChinaThe First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, ChinaThe First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaZhenjiang Hospital of Chinese Traditional and Western Medicine, Zhenjiang, Jiangsu, ChinaJiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, ChinaThe First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaJiangsu Collaborative Innovation Center of Traditional Chinese Medicine Prevention and Treatment of Tumor, Nanjing University of Chinese Medicine, Nanjing, ChinaThe First School of Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing, ChinaBackground: Colorectal cancer (CRC) is a malignancy with high incidence and mortality rates globally, categorized into left-sided and right-sided CRC, each exhibiting significant differences in molecular characteristics, clinical manifestations, and prognosis.Methods: This study employed single-cell transcriptomic data and various bioinformatics approaches, such as two-sample Mendelian randomization, reverse Mendelian randomization, colocalization analysis, directed filtering, pseudotime analysis, and intercellular communication analysis. It analyzed cellular-level disparities between left-sided and right-sided CRC, identifying distinct subpopulations with characteristic variations. For these cells, two-sample Mendelian randomization was utilized to explore gene-to-one-sided CRC causality.Results: LUCAT1 was enriched in high-abundance monocyte subpopulations in right-sided CRC and demonstrated potential risk factor status through Mendelian randomization analysis. The specific single-nucleotide polymorphism (SNP) rs10774624 was associated with an increased risk of CRC. Moreover, metabolic pathway analysis revealed that LUCAT1+ monocytes exhibit lower communication activity in the tumor microenvironment and heightened activity in metabolic functions like glycosaminoglycan degradation. Its biological functions are related to the positive regulation of interleukin-6 production and NF-kappa B signaling, among others.Conclusion: This study confirmed a potential causal relationship between LUCAT1 and right-sided CRC risk through Mendelian randomization analysis. These findings provide novel insights into the pathogenesis of right-sided CRC and may aid in developing early detection and treatment strategies for right-sided CRC.https://www.frontiersin.org/articles/10.3389/fgene.2024.1357704/fullcolorectal cancersingle-cell sequencingMendelian randomizedLUCAT1bioinformatics |
| spellingShingle | Zhihao Shang Zhihao Shang Songyang Xi Songyang Xi Songyang Xi Yueyang Lai Yueyang Lai Haibo Cheng Haibo Cheng Single-cell transcriptomics and Mendelian randomization reveal LUCAT1’s role in right-sided colorectal cancer risk Frontiers in Genetics colorectal cancer single-cell sequencing Mendelian randomized LUCAT1 bioinformatics |
| title | Single-cell transcriptomics and Mendelian randomization reveal LUCAT1’s role in right-sided colorectal cancer risk |
| title_full | Single-cell transcriptomics and Mendelian randomization reveal LUCAT1’s role in right-sided colorectal cancer risk |
| title_fullStr | Single-cell transcriptomics and Mendelian randomization reveal LUCAT1’s role in right-sided colorectal cancer risk |
| title_full_unstemmed | Single-cell transcriptomics and Mendelian randomization reveal LUCAT1’s role in right-sided colorectal cancer risk |
| title_short | Single-cell transcriptomics and Mendelian randomization reveal LUCAT1’s role in right-sided colorectal cancer risk |
| title_sort | single cell transcriptomics and mendelian randomization reveal lucat1 s role in right sided colorectal cancer risk |
| topic | colorectal cancer single-cell sequencing Mendelian randomized LUCAT1 bioinformatics |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2024.1357704/full |
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