5-hydroxymethylcytosine features of portal venous blood predict metachronous liver metastases of colorectal cancer and reveal phosphodiesterase 4 as a therapeutic target

Nuo Xu , Zhaoya Gao , Deyan Wu , Hangyu Chen , Zijian Zhang , Lei Zhang , Yuchen Wang , Xuyang Lu , Xu Yao , Xuelan Liu , Yi-You Huang , Meiying Qiu , Sen Wang , Jinqiang Liang , Can Mao , Feng Zhang , Huimin Xu , Yujiao Wang , Xian Li , Zhexin Chen , Dandan Huang , Jingyi Shi , Wensheng Huang , Fuming Lei , Zeruo Yang , Long Chen , Chuan He , Haichuan Zhu , Hai-Bin Luo , Jin Gu , Jian Lin

Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (2) : e70189

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Clinical and Translational Medicine ›› 2025, Vol. 15 ›› Issue (2) : e70189 DOI: 10.1002/ctm2.70189
RESEARCH ARTICLE

5-hydroxymethylcytosine features of portal venous blood predict metachronous liver metastases of colorectal cancer and reveal phosphodiesterase 4 as a therapeutic target

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Abstract

•5hmC epigenetic markers derived from portal venous blood could accurately predict metachronous metastasis of colorectal cancer.

•PDE4D was a key metastasis-driven target that promoted metachronous metastasis via the HIF-1α-CCN2 pathway.

•The newly synthesised compound L11 could specifically inhibit PDE4D and abolish metachronous metastasis of colorectal cancer without obvious toxic side effects.

Keywords

5hmC-Seal / Colorectal cancer / Metachronous liver metastases / PDE4D

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Nuo Xu, Zhaoya Gao, Deyan Wu, Hangyu Chen, Zijian Zhang, Lei Zhang, Yuchen Wang, Xuyang Lu, Xu Yao, Xuelan Liu, Yi-You Huang, Meiying Qiu, Sen Wang, Jinqiang Liang, Can Mao, Feng Zhang, Huimin Xu, Yujiao Wang, Xian Li, Zhexin Chen, Dandan Huang, Jingyi Shi, Wensheng Huang, Fuming Lei, Zeruo Yang, Long Chen, Chuan He, Haichuan Zhu, Hai-Bin Luo, Jin Gu, Jian Lin. 5-hydroxymethylcytosine features of portal venous blood predict metachronous liver metastases of colorectal cancer and reveal phosphodiesterase 4 as a therapeutic target. Clinical and Translational Medicine, 2025, 15(2): e70189 DOI:10.1002/ctm2.70189

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