Authors
Ying Liu, Clara Yieh Lin Chong, Yingrui Wang, Luang Xu, Hui Jun Lim, Qiu Xuan Tan, Josephine Hendrikson, Joey Wee-Shan Tan, Gillian Ng, Wanyu Guo, Youming Wang, Lingling Huang, Weigang Ge, Vinoth Kumar Rethineswaran, Jolynn Zu Lin Ong, Ying En Quek, Andre Jing Yuen Ang, Fionicca Teo, Oris Wanyi Chen, Ananya Rajesh, Yuwei Zhang, Tun Kiat Ko, Bavani Kannan, Boon Yee Lim, Elizabeth Chun Yong Lee, Zexi Guo, Vairavan Lakshmanan, Nicholas Brian Shannon, Nagalakshmi Jegannathan, Craig Ryan Joseph, Zhen Wei Neo, Li Yen Chong, Amanda R H Ng, Jia-Ying Joey Lee, Lit-Hsin Loo, Yang Wu, Siyu Zhang, Lanqi Nie, Qiqi Zhang, Lei Zeng, Tony Kiat Hon Lim, Matthew Chau Hsien Ng, Christabel Jing Zhi Lee, Pik Eu Jason Chang, Kevin Kim-Jun Teh, Hiang Keat Tan, Ravichandran Nadarajah, Tze Tein Yong, Junjie Wang, Ieera Madan Aggarwal, Eliza Li Shan Fong, Kenny Zhuoran Wu, Jimmy Bok Yan So, Khay Guan Yeoh, Jolene Si Min Wong, Chin Jin Seo, Mingzhe Cai, Claramae Shulyn Chia, Bin Tean Teh, Iain Beehuat Tan, Joe Yeong, Jason Yongsheng Chan, Tiannan Guo, Chin-Ann Johnny Ong, Singapore Peritoneal Oncology Study (SPOS) Group and Singapore Gastric Cancer Consortium (SGCC)
Published in
Molecular cancer. Volume 25. Issue 1. Sep 11, 2026. Epub Sep 11, 2026.
Abstract
Ascites in peritoneal metastases (PM) portends a poor prognosis. However, molecular ligands within ascites and their biological relevance remain unclear.
A comprehensive multiomic analysis, including proteomic analysis of 397 malignant cell-free ascites representing 21 histological origins of PM, was performed to decipher pertinent biological themes, identify and validate therapeutically relevant paracrine factors in cell-free ascites, and unravel cell-specific secretion of key paracrine factors. We further developed a nanobody targeting PAI-1 and tested it in vitro, in vivo and ex vivo human explant models.
Mass spectrometry analysis identified multiple biological themes including the coagulation cascade. New and previously identified paracrine factors amenable to therapeutic perturbation were also unraveled. Single-cell transcriptomic analysis confirmed secretion of two functionally antagonistic regulators of fibrinolysis (S100A10 and PAI-1) by distinct cell populations in PM ascites, suggesting upregulation of these ligands are due to active secretion by cells rather than homeostatic regulation. We also demonstrated proof of concept of efficacy with minimal toxicity of our nanobody against PAI-1.
Collectively, this study explores the biological significance of proteins in malignant cell-free ascites in PM and introduces the therapeutic potential of targeting PAI-1 via a nanobody.
PMID:
42778910
Bibliographic data and abstract were imported from PubMed on 24 Sep 2026.
Read full publication at:
Please sign in
to see all details.
Advertisement
Stats
- Recommendations n/a n/a positive of 0 vote(s)
- Views 6
- Comments 0