ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
This article is part of the Research TopicMetabolic Crossroads: Decoding the Immune-Tumor Interface for Therapeutic BreakthroughsView all 6 articles
FAM-related prognostic molecular subtypes screening identified epithelial-derived MAOA inhibiting bladder cancer
Provisionally accepted
Hui Yu1
雷庆强 雷庆强2Wenyong Yang1Min Cao1
Miaoyu Zhang1Taisong Wang1Junhao Dong1Xuerui Chen1
Xu Su1
Yi Huang1He Xu1Hui Zhuo1
Liangbin Lin1*- 1Southwest Jiaotong University, Chengdu, China
- 2Army Medical University, Chongqing, China
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Fatty acid metabolism (FAM) plays a critical role in cancer cell proliferation and progression by supporting membrane synthesis, energy storage, and signaling molecule production. However, strategies to target this process have not yet translated into clinical practice. Here we constructed a novel four-gene FAM-RiskScore (FAMR) signature (PATZ1, TTC6, AEBP1, and MAOA) based on FAM-related genes to predict bladder cancer prognosis. Cluster analysis based on the 158 FAM-related genes classified the 359 bladder cancer (BLCA) samples into two subtypes, C1 and C2. C1 had better overall survival compared with C2. Biological functional analysis revealed that C1 is related to enhanced steroid metabolism and down-regulated chemokine signaling, as well as lower immune score. The FAM-RiskScore (FAMR) model was validated using both internal and external validation cohort. According to the model, low expression of PATZ1, TTC6, MAOA, and high expression of AEBP1 were correlated with high FAMR value, as well as poor prognosis, indicating the higher FAMR represented the poorer prognosis. Further analysis demonstrated that FAMR positively correlated with pathways involving chemotaxis, cytoskeleton regulation, infections, and inflammation, while negatively correlating with fatty acid metabolism pathways. Notably, higher FAMR values were observed in female patients, individuals aged >60, and advanced-stage (II–IV) tumors, all of which were associated with poorer prognosis. Besides, single-cell RNA-seq data revealed that AEBP1 and MAOA were CAF-derived and cancer cell-derived respectively. Functional studies revealed that MAOA knockdown significantly promoted the proliferation and migration capacities of T24 and 5637 bladder cancer cells in vitro. Together, our study identified the novel FAMR model for BLCA prognosis prediction, and MAOA as an inhibitory gene of bladder cancer proliferation and migration, which may benefit the optimization of clinical therapy strategies.
Keywords: Bladder cancer, fatty acid metabolism, MAOA, Prognosis prediction, single-cell RNA-seq
Received: 27 Oct 2025; Accepted: 02 Feb 2026.
Copyright: © 2026 Yu, 雷庆强, Yang, Cao, Zhang, Wang, Dong, Chen, Su, Huang, Xu, Zhuo and Lin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Liangbin Lin
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