The interplay between tissue-resident microbiome and host proteins by integrated multi-omics during progression of colorectal adenoma to carcinoma
文献类型：期刊论文
| 作者 | Wu, Di1; Wang, An-Jun1,2; Bu, De-Chao3,4; Sun, Yan-Yan1; Li, Chen-Hao3,4; Hong, Yue-Mei1; Zhang, Shan3,4; Chen, Shi-Yang5; Zhou, Jin-An1; Zhang, Tian-Yi1 |
| 刊名 | IMETA
 |
| 出版日期 | 2025-11-04 |
| 页码 | 37 |
| 关键词 | colorectal cancer metagenomics microbiota-host interaction proteomics tissue-resident microbiome |
| ISSN号 | 2770-5986 |
| DOI | 10.1002/imt2.70090 |
| 英文摘要 | 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. |
| 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 |
| 语种 | 英语 |
| WOS记录号 | WOS:001607550900001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.204/handle/2XEOYT63/41604]  |
| 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 |
| 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. |
入库方式： OAI收割
来源：计算技术研究所
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