Multi-omics analysis reveals a pericyte-associated gene expression signature for predicting prognosis and therapeutic responses in solid cancers.

Autor:	Kong X; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China., Zhuo X; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Department of Otolaryngology, Head and Neck Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, China., Huang X; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China., Shang L; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China., Lan T; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Department of Oral and Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510010, China., Qin H; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China., Chen X; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China., Lv C; Clinical Biobank Center, Zhujiang Hospital, Southern Medical University, Guangzhou 510280, China. Electronic address: lvcui@smu.edu.cn., Xu Q; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. Electronic address: xuqp3@mail.sysu.edu.cn., Wong PP; Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangdong-Hong Kong Joint Laboratory for RNA Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China; Medical Research Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510120, China. Electronic address: huangbp3@mail.sysu.edu.cn.
Jazyk:	angličtina
Zdroj:	Genomics [Genomics] 2024 Sep; Vol. 116 (5), pp. 110942. Date of Electronic Publication: 2024 Sep 24.
DOI:	10.1016/j.ygeno.2024.110942
Abstrakt:	The influence of the stroma on cancer progression has been underestimated, particularly the role of vascular pericytes in the tumor microenvironment. Herein, we identified 51 differentially expressed genes in tumor-derived pericytes (TPCs) by analyzing transcriptomic data from TCGA alongside our proteomic data. Using five key TPC-related genes, we constructed a prognostic risk model that accurately predicts prognosis and treatment responses in liver and lung cancers. Enrichment analyses linked these genes to blood vessel remodeling, function, and immune-related pathways. Single-cell RNA sequencing data from the GEO database validated these findings, showing significant upregulation of AKAP12 and RRAS in TPCs. Immunostaining confirmed increased expression of these genes in liver and lung tumors. Depletion of RRAS or AKAP12 in TPCs restored their blood vessel-supporting role. Overall, our findings suggest that TPC-related gene profiles can predict patient outcomes and therapeutic responses in solid cancers, and targeting these profiles could be an improved treatment strategy. Competing Interests: Declaration of competing interest None of the authors has a conflict of interests. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Full Text from ScienceDirect