FFPE試料向け新規マルチオミクス手法を開発し前立腺がんの不均一性を解明(Researchers Develop Novel Multi-omics Approach for FFPE Samples and Elucidate Heterogeneity of Prostate Cancer)

ad

2026-02-27 中国科学院(CAS)

前立腺がんは男性に多い悪性腫瘍で、アンドロゲン‐受容体(AR)経路を標的とする治療が中心だが、腫瘍内不均一性により耐性が課題となる。中国科学院分子細胞科学卓越創新中心のLI Zhenfei研究グループは、FFPE検体に適用可能なsnFLARE-seqおよびmxFRIZNGRND法を開発し、488例を解析。さらに14病変で単一核トランスクリプトーム(10万超細胞)と1,773代謝物のマルチオミクス解析を実施した。末梢帯(PZ)由来や多区域にまたがる腫瘍は進行が速く薬剤耐性化しやすいこと、ホルモン療法が上皮細胞をより攻撃的表現型へ転換させ免疫抑制的微小環境を形成することを解明。4つの主要代謝経路と関連遺伝子を同定し、精密医療への基盤を示した。

<関連情報>

snFLARE-seqとmxFRIZNGRNDを用いた、解剖学的起源の異なる前立腺癌のトランスクリプトームおよびメタボロームの解析 Analysis of the transcriptomic and metabolomic landscape of prostate cancer with different anatomical origins using snFLARE-seq and mxFRIZNGRND

Dongyin He  (何东印),Haoran Hu  (胡浩然),Kai Xiao  (肖楷),Yuhang Zhang  (张宇航),Yongbing Cheng  (程勇兵),Shaozhuo Jiao  (焦少灼),Yimei Hao  (郝一妹),Yuanyuan Cai  (蔡园园),Ziqun Liu  (刘子群),Xinran Yan  (颜欣然),Qinsheng Chen  (陈钦盛),Xiyan Mu  (穆希岩),Qi Wang  (王琪),Shan Peng  (彭姗),Guoqin Sang  (桑国芹),Xiaoling Zhi  (职小玲),Yanxia Chang  (常燕霞),Qing Ye  (叶青),Yuyao Yang  (杨羽尧),Meixia Che  (车美霞),Shengsong Huang  (黄盛松),Hongqian Guo  (郭宏骞),Luonan Chen  (陈洛南),Huiru Tang  (唐惠儒),… Zhenfei Li  (李振斐)
Nature Communications  Published:07 February 2026
DOI:https://doi.org/10.1038/s41467-026-69347-7  Unedited version

Abstract

Prostate cancer cells of different anatomical locations display remarkable heterogeneity. This poses a challenge to the clinical relevance of pre-clinical models and the efficacy of contemporary therapeutic approaches. Here we develop the snFLARE-seq and mxFRIZNGRND methodologies to directly investigate the transcriptomic and metabolomic landscape of prostate cancer patients utilizing formalin-fixed paraffin-embedded (FFPE) specimens. A retrospective analysis reveals the clinical disparities of prostate cancer from peripheral zone (PZ), transition zone (TZ), and across PZ and TZ. The snFLARE-seq, refined for enhanced single-nucleus sequencing, unveils distinct cell type distributions and signaling pathways between PZ and TZ samples. Hormone therapy substantially affects cancer cells and microenvironment, leading to a polarized feature of epithelial cells and a subverted immune microenvironment. With improvements in metabolite extraction, mxFRIZNGRND reveals unique metabolic features of prostate cancer from different origins. The metabolomic results indicate that PZ cancer cells are in a metabolic-dormant status, which are probably awaken by hormone therapy. Integrative analysis of results from snFLARE-seq, mxFRIZNGRND, and TCGA database uncovers four metabolic pathways and related genes associated with disease aggressiveness. Our work could accelerate investigations on disease heterogeneity and evolution in real-world clinical settings, stimulating patient-specific precision healthcare solutions.

医療・健康
ad
ad
Follow
ad
タイトルとURLをコピーしました