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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2025 The Author(s). Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.

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