详情页 - 四川省肿瘤医院知识库

当前位置：首页 > 详情页

Phenotypic heterogeneity analysis of APC-mutant colon cancer by proteomics and phosphoproteomics identifies RAI14 as a key prognostic determinant in East Asians and Westerners

文献详情

资源类型：

Pubmed体系：

作者：

机构： [1]National Clinical Research Center for Geriatrics and General Practice Medical Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. [2]Colorectal Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China. [3]West China-Washington Mitochondria and Metabolism Centre, Institutes for Systems Genetics [4]Advanced Mass Spectrometry Center, Research Core Facility, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, China. [5]The First Clinical Medical College, Lanzhou University, Lanzhou, 730000, China. [6]Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.

出处：

DOI：

ISSN：

摘要：

Adenomatous polyposis coli (APC) is an important tumor suppressor and is mostly linked to the regulation of the WNT/β-catenin signaling pathway. APC mutation has been identified as an early event in more than 80% of sporadic colorectal cancers (CRCs). Moreover, prognostic differences are observed in CRC patients with APC mutations. Although previous genomics studies have investigated the roles of concomitant gene mutations in determining the phenotypic heterogeneity of APC-mutant tumors, valuable prognostic determinants for APC-mutant CRC patients are still lacking. Based on the proteome and phosphoproteome data, we classified APC-mutant colon cancer patients and revealed genomic, proteomic and phosphoproteomic heterogeneity in APC-mutant tumors. More importantly, we identified RAI14 as a key prognostic determinant for APC-mutant but not APC-wildtype colon cancer patients. The heterogeneity and the significance of prognostic biomarkers in APC-mutant tumors were further validated in the Clinical Proteomic Tumor Analysis Consortium (CPTAC) colon cancer cohort. In addition, we found that colon cancer patients with high expression of RAI14 were less responsive to chemotherapy. Knockdown of RAI14 in cell lines led to reduced cell migration and changes in epithelial-mesenchymal transition (EMT)-related markers. Mechanistically, knockdown of RAI14 remodeled the phosphoproteome associated with cell adhesion, which might affect EMT marker expression and promote F-actin degradation. Collectively, this work describes the phenotypic heterogeneity of APC-mutant tumors and identifies RAI14 as an important prognostic determinant for APC-mutant colon cancer patients. The prognostic utility of RAI14 in APC-mutant colon cancer will provide early warning and increase the chance of successful treatment.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

基金：

语种：

PubmedID：

中科院(CAS)分区：

出版当年[2023]版：

大类 | 2 区生物学

小类 | 1 区生化研究方法

最新[2023]版：

大类 | 2 区生物学

小类 | 1 区生化研究方法

第一作者：

第一作者机构： [1]National Clinical Research Center for Geriatrics and General Practice Medical Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.

共同第一作者：

通讯作者：

通讯机构： [2]Colorectal Cancer Center, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China. [6]Institute of Digestive Surgery, West China Hospital, Sichuan University, Chengdu, 610041, China.

推荐引用方式(GB/T 7714)：

APA：

MLA：