Please use this identifier to cite or link to this item:
Title: Integrated multi-omics identified the novel intratumor microbiome-derived subtypes and signature to predict the outcome, tumor microenvironment heterogeneity, and immunotherapy response for pancreatic cancer patients
Author(s): Zhang, Biao
Liu, JifengLook up in the Integrated Authority File of the German National Library
Li, Han
Huang, Bingqian
Zhang, Bolin
Song, BinyuLook up in the Integrated Authority File of the German National Library
Bao, Chongchan
Liu, Yunfei
Wang, Zhizhou
Issue Date: 2023
Type: Article
Language: English
Abstract: Background: The extremely malignant tumour known as pancreatic cancer (PC) lacks efficient prognostic markers and treatment strategies. The microbiome is crucial to how cancer develops and responds to treatment. Our study was conducted in order to better understand how PC patients’ microbiomes influence their outcome, tumour microenvironment, and responsiveness to immunotherapy. Methods: We integrated transcriptome and microbiome data of PC and used univariable Cox regression and Kaplan–Meier method for screening the prognostic microbes. Then intratumor microbiome-derived subtypes were identified using consensus clustering. We utilized LASSO and Cox regression to build the microbe-related model for predicting the prognosis of PC, and utilized eight algorithms to assess the immune microenvironment feature. The OncoPredict package was utilized to predict drug treatment response. We utilized qRT-PCR to verify gene expression and single-cell analysis to reveal the composition of PC tumour microenvironment. Results: We obtained a total of 26 prognostic genera in PC. And PC samples were divided into two microbiome-related subtypes: Mcluster A and B. Compared with Mcluster A, patients in Mcluster B had a worse prognosis and higher TNM stage and pathological grade. Immune analysis revealed that neutrophils, regulatory T cell, CD8+ T cell, macrophages M1 and M2, cancer associated fibroblasts, myeloid dendritic cell, and activated mast cell had remarkably higher infiltrated levels within the tumour microenvironment of Mcluster B. Patients in Mcluster A were more likely to benefit from CTLA-4 blockers and were highly sensitive to 5-fluorouracil, cisplatin, gemcitabine, irinotecan, oxaliplatin, and epirubicin. Moreover, we built a microbe-derived model to assess the outcome. The ROC curves showed that the microbe-related model has good predictive performance. The expression of LAMA3 and LIPH was markedly increased within pancreatic tumour tissues and was linked to advanced stage and poor prognosis. Single-cell analysis indicated that besides cancer cells, the tumour microenvironment of PC was also rich in monocytes/macrophages, endothelial cells, and fibroblasts. LIPH and LAMA3 exhibited relatively higher expression in cancer cells and neutrophils. Conclusion: The intratumor microbiome-derived subtypes and signature in PC were first established, and our study provided novel perspectives on PC prognostic indicators and treatment options.
Open Access: Open access publication
License: (CC BY 4.0) Creative Commons Attribution 4.0(CC BY 4.0) Creative Commons Attribution 4.0
Journal Title: Frontiers in pharmacology
Publisher: Frontiers Media
Publisher Place: Lausanne
Volume: 14
Original Publication: 10.3389/fphar.2023.1244752
Page Start: 1
Page End: 19
Appears in Collections:Open Access Publikationen der MLU

Files in This Item:
File Description SizeFormat 
fphar-14-1244752.pdf7.98 MBAdobe PDFThumbnail