The interplay between tissue-resident microbiome and host proteins by integrated multi-omics during progression of colorectal adenoma to carcinoma

doi:10.1002/imt2.70090

	The interplay between tissue-resident microbiome and host proteins by integrated multi-omics during progression of colorectal adenoma to carcinoma
	Wu, Di 1; Wang, An-Jun 1,2; Bu, De-Chao 3,4; Sun, Yan-Yan 1; Li, Chen-Hao 3,4; Hong, Yue-Mei 1; Zhang, Shan 3,4; Chen, Shi-Yang 5; Zhou, Jin-An 1; Zhang, Tian-Yi 1; Yu, Min-Hao 6; Ma, Yong-Jing 1; Wang, Xiu-Li 1; Xu, Jia 6; He, Wei 7; Heeschen, Christopher 1; Chen, Jian-Feng 5,8; Mao, Wen-Jun 9,10; Ding, Hui 11,12; Wu, Wen-Juan 13; Zhao, Yi 3,4; Wang, Hui 1,14; Liu, Ning-Ning 1
	2025-11-04
发表期刊	IMETA
ISSN	2770-5986
页码	37
摘要	The intratumoral microbiome is an emerging hallmark of cancer, yet its multi-kingdom host-microbiome ecosystem in colorectal cancer (CRC) remains poorly characterized. Here, we conducted an integrated analysis using deep shotgun metagenomics and proteomics on 185 tissue samples, including adenoma (A), paired tumor (T), and para-tumor (P). We identified 4057 bacterial, 61 fungal, 108 archaeal, and 374 viral species in tissues and revealed distinct intratumor microbiota dysbiosis, indicating a CRC-specific multi-kingdom microbial ecosystem. Proteomic profiling uncovered four CRC subtypes (C1-C4), each with unique clinical prognoses and molecular signatures. We further discovered that host-microbiome interactions are dynamically reorganized during carcinogenesis, where different microbial taxa converge on common host pathways through distinct proteins. Leveraging this interplay, we identified 14 multi-kingdom microbial and 8 protein markers that strongly distinguished A from T samples (area under the receiver operating characteristic curve (AUROC) = 0.962), with external validation in two independent datasets (AUROC = 0.920 and 0.735). Moreover, we constructed an early- versus advanced-stage classifier using 8 microbial and 4 protein markers, which demonstrated high diagnostic accuracy (AUROC = 0.926) and was validated externally (AUROC = 0.659-0.744). Functional validation in patient-derived organoids and murine allograft models confirmed that enterotoxigenic Bacteroides fragilis and Fusobacterium nucleatum promoted tumor growth by activating Wnt/beta-catenin and NF-kappa B signaling pathways, corroborating the functional potential of these biomarkers. Together, these findings reveal dynamic host-microbiome interactions at the protein level, tracing the transition from adenoma to carcinoma and offering potential diagnostic and therapeutic targets for CRC.
关键词	colorectal cancer metagenomics microbiota-host interaction proteomics tissue-resident microbiome
DOI	10.1002/imt2.70090
收录类别	SCI
语种	英语
资助项目	Computational Biology Program of Science and Technology Commission of Shanghai Municipality (STCSM)[25JS2810200] ; Natural Science Foundation of China[32422004] ; Natural Science Foundation of China[32270202] ; Natural Science Foundation of China[82030099] ; Program of Shanghai Academic Research Leader[23XD1422300] ; MOST Key R&D Program of China[2022YFC2304703] ; MOST Key R&D Program of China[2020YFA0907200] ; Medicine and Engineering Interdisciplinary Research Fund of Shanghai Jiao Tong University[24X010301328] ; Innovative Research Team of High-level Local University in Shanghai
WOS研究方向	Microbiology
WOS类目	Microbiology
WOS记录号	WOS:001607550900001
出版者	WILEY
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.204/handle/2XEOYT63/41605
专题	中国科学院计算技术研究所期刊论文_英文
通讯作者	Mao, Wen-Jun; Ding, Hui; Wu, Wen-Juan; Zhao, Yi; Wang, Hui; Liu, Ning-Ning
作者单位	1.Shanghai Jiao Tong Univ, Sch Med, Ctr Single Cell Om, Sch Publ Hlth,State Key Lab Syst Med Canc, Shanghai 200025, Peoples R China 2.Shanghai Xuhui Hlth Inspect Agcy, Shanghai Xuhui Ctr Dis Prevent & Control, Shanghai, Peoples R China 3.Chinese Acad Sci, Inst Comp Technol, Res Ctr Ubiquitous Comp Syst, Beijing 100190, Peoples R China 4.Univ Chinese Acad Sci, Beijing, Peoples R China 5.Univ Chinese Acad Sci, Hangzhou Inst Adv Study, Sch Life Sci, Key Lab Syst Hlth Sci Zhejiang Prov, Hangzhou, Peoples R China 6.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Gastrointestinal Surg, Shanghai, Peoples R China 7.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Pathol, Shanghai, Peoples R China 8.Fudan Univ, Sch Basic Med Sci, Dept Immunol, Shanghai, Peoples R China 9.Nanjing Med Univ, Wuxi Med Ctr, Wuxi Peoples Hosp, Dept Thorac Surg,Affiliated Wuxi Peoples Hosp, Wuxi 214002, Peoples R China 10.Nanjing Med Univ, Affiliated Wuxi Peoples Hosp, Ctr Clin Res, Wuxi Med Ctr,Wuxi Peoples Hosp, Wuxi, Peoples R China 11.Shanghai Jiao Tong Univ, Sch Med, Renji Hosp, Dept Gastroenterol & Hepatol, Shanghai 200127, Peoples R China 12.Shanghai Inst Digest Dis, NHC Key Lab Digest Dis, Shanghai, Peoples R China 13.Tongji Univ, Sch Med, Shanghai East Hosp, Dept Lab Med, Shanghai 200123, Peoples R China 14.Shanghai Jiao Tong Univ, Hainan Int Med Ctr, Sch Med, Haikou, Hainan, Peoples R China
推荐引用方式 GB/T 7714	Wu, Di,Wang, An-Jun,Bu, De-Chao,et al. The interplay between tissue-resident microbiome and host proteins by integrated multi-omics during progression of colorectal adenoma to carcinoma[J]. IMETA,2025:37.
APA	Wu, Di.,Wang, An-Jun.,Bu, De-Chao.,Sun, Yan-Yan.,Li, Chen-Hao.,...&Liu, Ning-Ning.(2025).The interplay between tissue-resident microbiome and host proteins by integrated multi-omics during progression of colorectal adenoma to carcinoma.IMETA,37.
MLA	Wu, Di,et al."The interplay between tissue-resident microbiome and host proteins by integrated multi-omics during progression of colorectal adenoma to carcinoma".IMETA (2025):37.