Data mining identifies novel RNA-binding proteins involved in colon and rectal carcinomas

Frontiers in Cell and Developmental Biology

Cell and Developmental Biology

Nathali García-Cárdenas¹  Santiago Guerrero²  Jennyfer M. García-Cárdenas²  Isaac Armendáriz-Castillo³  Andrés López-Cortés⁴  Alberto Indacochea⁵  David Pesantez-Coronel⁵ 

[1] Instituto Nacional de Investigación en Salud Pública, Quito, Ecuador;Laboratorio de Ciencia de Datos Biomédicos, Escuela de Medicina, Facultad de Ciencias Médicas de la Salud y de la Vida, Universidad Internacional del Ecuador, Quito, Ecuador;Latin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Madrid, Spain;Laboratorio de Ciencia de Datos Biomédicos, Escuela de Medicina, Facultad de Ciencias Médicas de la Salud y de la Vida, Universidad Internacional del Ecuador, Quito, Ecuador;Latin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Madrid, Spain;Facultad de Ingenierías y Ciencias Aplicadas, Universidad Internacional SEK, Quito, Ecuador;Latin American Network for the Implementation and Validation of Clinical Pharmacogenomics Guidelines (RELIVAF-CYTED), Madrid, Spain;Cancer Research Group (CRG), Faculty of Medicine, Universidad de Las Américas, Quito, Ecuador;Medical Oncology Department Hospital Clinic and Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, Barcelona, Spain;

关键词: RNA-binding proteins (RBPs);    colorectal adenocarcinoma (COREAD);    rectum;    colon;    biomarkers;    cancer;    data mining;    multi-omics;   

DOI  :  10.3389/fcell.2023.1088057

 received in 2022-11-03, accepted in 2023-02-13,  发布年份 2023

来源: Frontiers

【 摘 要 】

Colorectal adenocarcinoma (COREAD) is the second most deadly cancer and third most frequently encountered malignancy worldwide. Despite efforts in molecular subtyping and subsequent personalized COREAD treatments, multidisciplinary evidence suggests separating COREAD into colon cancer (COAD) and rectal cancer (READ). This new perspective could improve diagnosis and treatment of both carcinomas. RNA-binding proteins (RBPs), as critical regulators of every hallmark of cancer, could fulfill the need to identify sensitive biomarkers for COAD and READ separately. To detect new RBPs involved in COAD and READ progression, here we used a multidata integration strategy to prioritize tumorigenic RBPs. We analyzed and integrated 1) RBPs genomic and transcriptomic alterations from 488 COAD and 155 READ patients, 2) ∼ 10,000 raw associations between RBPs and cancer genes, 3) ∼ 15,000 immunostainings, and 4) loss-of-function screens performed in 102 COREAD cell lines. Thus, we unraveled new putative roles of NOP56, RBM12, NAT10, FKBP1A, EMG1, and CSE1L in COAD and READ progression. Interestingly, FKBP1A and EMG1 have never been related with any of these carcinomas but presented tumorigenic features in other cancer types. Subsequent survival analyses highlighted the clinical relevance of FKBP1A, NOP56, and NAT10 mRNA expression to predict poor prognosis in COREAD and COAD patients. Further research should be performed to validate their clinical potential and to elucidate their molecular mechanisms underlying these malignancies.

【 授权许可】

Unknown   
Copyright © 2023 García-Cárdenas, Armendáriz-Castillo, García-Cárdenas, Pesantez-Coronel, López-Cortés, Indacochea and Guerrero.