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

doi:10.1002/ctm2.70189

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

Nuo Xu ¹^,²
, Zhaoya Gao ³^,⁴
, Deyan Wu ⁵
, Hangyu Chen ¹
, Zijian Zhang ⁵
, Lei Zhang ²
, Yuchen Wang ²
, Xuyang Lu ²
, Xu Yao ²
, Xuelan Liu ²
, Yi-You Huang ⁵
, Meiying Qiu ⁶
, Sen Wang ⁵
, Jinqiang Liang ⁵
, Can Mao ⁵
, Feng Zhang ⁵
, Huimin Xu ⁵
, Yujiao Wang ⁵
, Xian Li ⁵
, Zhexin Chen ⁵
, Dandan Huang ⁴^,⁷
, Jingyi Shi ⁸
, Wensheng Huang ³^,⁴
, Fuming Lei ³^,⁴
, Zeruo Yang ¹
, Long Chen ¹
, Chuan He ⁹
, Haichuan Zhu ¹⁰^,^†
, Hai-Bin Luo ⁵^,^†
, Jin Gu ³^,⁸^,⁴^,¹¹^,^†
, Jian Lin ¹^,¹²^,¹³^,¹⁴^,^†

Author information +

¹. Department of Pharmacy, Peking University Third Hospital, Beijing, China

². Natural Medicine Institute of Zhejiang YangShengTang Co. Ltd., Hangzhou, China

³. Department of Gastrointestinal Surgery, Peking University Shougang Hospital, Beijing, China

⁴. Center for Precision Diagnosis and Treatment of Colorectal Cancer and Inflammatory Diseases, Peking University Health Science Center, Beijing, China

⁵. Key Laboratory of Tropical Biological Resources of Ministry of Education, School of Pharmaceutical Sciences, Hainan University, Haikou, Hainan, China

⁶. School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China

⁷. Department of Oncology, Peking University Shougang Hospital, Beijing, China

⁸. Key laboratory of Carcinogenesis & Translational Research (Ministry of Education), Department of Gastrointestinal Surgery III, Peking University Cancer Hospital & Institute, Beijing, China

⁹. Department of Chemistry, Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, The University of Chicago, Chicago, Illinois, USA

¹⁰. Institute of Biology and Medicine, College of Life and Health Sciences, Wuhan University of Science and Technology, Wuhan, China

¹¹. Peking University International Cancer Institute, Peking University, Beijing, China

¹². Peking University Third Hospital Cancer Center, Peking University Third Hospital, Beijing, China

¹³. Synthetic and Functional Biomolecules Center, Peking University, Beijing, China

¹⁴. Key Laboratory of Tropical Biological Resources of Ministry of Education, Song Li’s AcademicianWorkstation of Hainan University, School of Pharmaceutical Sciences, Hainan University, Haikou, China

zhuhaichuan@wust.edu.cn

hbluo@hainanu.edu.cn

zlguj@bjmu.edu.cn

linjian@pku.edu.cn

Show less

History +

PDF

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

Cite this article

Download citation ▾

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

登录浏览全文

4963

注册一个新账户忘记密码

References

Publishing order | Descend order by publishing year | Descend order by cited within

RIGHTS & PERMISSIONS

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