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Investigating the Cell Origin and Liver Metastasis Factors of Colorectal Cancer by Single-Cell Transcriptome Analysis.

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Title: Investigating the Cell Origin and Liver Metastasis Factors of Colorectal Cancer by Single-Cell Transcriptome Analysis.
Authors: Sha, Zhilin (AUTHOR), Gao, Qingxiang (AUTHOR), Wang, Lei (AUTHOR), An, Ni (AUTHOR), Wu, Yingjun (AUTHOR), Wei, Dong (AUTHOR), Wang, Tong (AUTHOR), Liu, Chen (AUTHOR), Shen, Yang (AUTHOR)
Source: OncoTargets & Therapy. Apr2024, Vol. 17, p345-358. 14p.
Subject Terms: *COLORECTAL liver metastasis, *WNT/BETA-catenin pathway, *LIVER cells, *MACHINE learning, *LIVER metastasis, *WNT genes, *GENE clusters
Abstract: Background: Colorectal cancer (CRC) is one of the deadliest causes of death by cancer worldwide. Liver metastasis (LM) is the main cause of death in patients with CRC. Therefore, identification of patients with the greatest risk of liver metastasis is critical for early treatment and reduces the mortality of patients with colorectal cancer liver metastases. Methods: Initially, we characterized cell composition through single-cell transcriptome analysis. Subsequently, we employed copy number variation (CNV) and pseudotime analysis to delineate the cellular origins of LM and identify LM-related epithelial cells (LMECs). The LM-index was constructed using machine learning algorithms to forecast the relative abundance of LMECs, reflecting the risk of LM. Furthermore, we analyzed drug sensitivity and drug targeted gene expression in LMECs and patients with a high risk of LM. Finally, functional experiments were conducted to determine the biological roles of metastasis-related gene in vitro. Results: Single-cell RNA sequencing analysis revealed different immune landscapes between primary CRC and LM tumor. LM originated from chromosomal variants with copy number loss of chr1 and chr6p and copy number gain of chr7 and chr20q. We identified the LMECs cluster and found LM-associated pathways such as Wnt/beta-catenin signaling and KRAS signaling. Subsequently, we identified ten metastasis-associated genes, including SOX4, and established the LM-index, which correlates with poorer prognosis, higher stage, and advanced age. Furthermore, we screened two drugs as potential candidates for treating LM, including Linsitinib_1510, Lapatinib_1558. Immunohistochemistry results demonstrated significantly elevated SOX4 expression in tumor samples compared to normal samples. Finally, in vitro experiments verified that silencing SOX4 significantly inhibited tumor cell migration and invasion. Conclusion: This study reveals the possible cellular origin and driving factors of LM in CRC at the single cell level, and provides a reference for early detection of CRC patients with a high risk of LM. [ABSTRACT FROM AUTHOR]
Copyright of OncoTargets & Therapy is the property of Dove Medical Press Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Investigating the Cell Origin and Liver Metastasis Factors of Colorectal Cancer by Single-Cell Transcriptome Analysis.
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  Data: <searchLink fieldCode="AR" term="%22Sha%2C+Zhilin%22">Sha, Zhilin</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gao%2C+Qingxiang%22">Gao, Qingxiang</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Lei%22">Wang, Lei</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22An%2C+Ni%22">An, Ni</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wu%2C+Yingjun%22">Wu, Yingjun</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wei%2C+Dong%22">Wei, Dong</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Wang%2C+Tong%22">Wang, Tong</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Liu%2C+Chen%22">Liu, Chen</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Shen%2C+Yang%22">Shen, Yang</searchLink> (AUTHOR)
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  Data: <searchLink fieldCode="JN" term="%22OncoTargets+%26+Therapy%22">OncoTargets & Therapy</searchLink>. Apr2024, Vol. 17, p345-358. 14p.
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  Data: *<searchLink fieldCode="DE" term="%22COLORECTAL+liver+metastasis%22">COLORECTAL liver metastasis</searchLink><br />*<searchLink fieldCode="DE" term="%22WNT%2FBETA-catenin+pathway%22">WNT/BETA-catenin pathway</searchLink><br />*<searchLink fieldCode="DE" term="%22LIVER+cells%22">LIVER cells</searchLink><br />*<searchLink fieldCode="DE" term="%22MACHINE+learning%22">MACHINE learning</searchLink><br />*<searchLink fieldCode="DE" term="%22LIVER+metastasis%22">LIVER metastasis</searchLink><br />*<searchLink fieldCode="DE" term="%22WNT+genes%22">WNT genes</searchLink><br />*<searchLink fieldCode="DE" term="%22GENE+clusters%22">GENE clusters</searchLink>
– Name: Abstract
  Label: Abstract
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  Data: Background: Colorectal cancer (CRC) is one of the deadliest causes of death by cancer worldwide. Liver metastasis (LM) is the main cause of death in patients with CRC. Therefore, identification of patients with the greatest risk of liver metastasis is critical for early treatment and reduces the mortality of patients with colorectal cancer liver metastases. Methods: Initially, we characterized cell composition through single-cell transcriptome analysis. Subsequently, we employed copy number variation (CNV) and pseudotime analysis to delineate the cellular origins of LM and identify LM-related epithelial cells (LMECs). The LM-index was constructed using machine learning algorithms to forecast the relative abundance of LMECs, reflecting the risk of LM. Furthermore, we analyzed drug sensitivity and drug targeted gene expression in LMECs and patients with a high risk of LM. Finally, functional experiments were conducted to determine the biological roles of metastasis-related gene in vitro. Results: Single-cell RNA sequencing analysis revealed different immune landscapes between primary CRC and LM tumor. LM originated from chromosomal variants with copy number loss of chr1 and chr6p and copy number gain of chr7 and chr20q. We identified the LMECs cluster and found LM-associated pathways such as Wnt/beta-catenin signaling and KRAS signaling. Subsequently, we identified ten metastasis-associated genes, including SOX4, and established the LM-index, which correlates with poorer prognosis, higher stage, and advanced age. Furthermore, we screened two drugs as potential candidates for treating LM, including Linsitinib_1510, Lapatinib_1558. Immunohistochemistry results demonstrated significantly elevated SOX4 expression in tumor samples compared to normal samples. Finally, in vitro experiments verified that silencing SOX4 significantly inhibited tumor cell migration and invasion. Conclusion: This study reveals the possible cellular origin and driving factors of LM in CRC at the single cell level, and provides a reference for early detection of CRC patients with a high risk of LM. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of OncoTargets & Therapy is the property of Dove Medical Press Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Value: 10.2147/OTT.S454295
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        Text: English
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        PageCount: 14
        StartPage: 345
    Subjects:
      – SubjectFull: COLORECTAL liver metastasis
        Type: general
      – SubjectFull: WNT/BETA-catenin pathway
        Type: general
      – SubjectFull: LIVER cells
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      – SubjectFull: MACHINE learning
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      – SubjectFull: LIVER metastasis
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      – SubjectFull: WNT genes
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      – SubjectFull: GENE clusters
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      – TitleFull: Investigating the Cell Origin and Liver Metastasis Factors of Colorectal Cancer by Single-Cell Transcriptome Analysis.
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            – D: 01
              M: 04
              Text: Apr2024
              Type: published
              Y: 2024
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