Multi-Omic Analysis of Esophageal Adenocarcinoma Uncovers Candidate Therapeutic Targets and Cancer-Selective Posttranscriptional Regulation

作者：J. Robert O’Neill, Marcos Yébenes Mayordomo, Goran Mitulović, Sofian Al Shboul, Georges Bedran, Jakub Faktor, Lenka Hernychová, Lukáš Uhrík, Maria Gómez-Herranz, Mikołaj Kocikowski, Vicki Save, Bořivoj Vojtěšek, Mark J. Arends, Rebecca C. Fitzgerald, Paul A. Edwards, Nicola Grehan, Barbara Nutzinger, Christine Loreno, Aisling M. Redmond, Sujath Abbas, Adam Freeman, Elizabeth Smyth, Maria O’Donovan, Ahmad Miremadi, Shalini Malhotra, Monika Tripathi, Calvin Cheah, Hannah Coles, Curtis Millington, Ginny Devonshire, Matthew Eldridge, Maria Secrier, Sriganesh Jammula, Jim Davies, Charles Crichton, Nick Carroll, Richard Hardwick, Peter Safranek, Andrew Hindmarsh, Vijayendran Sujendran, Stephen J. Hayes, Yeng Ang, Andrew D. Sharrocks, Shaun R. Preston, Izhar Bagwan, Vicki Save, Richard J.E. Skipworth, Ted R. Hupp, J. Robert O’Neill, Olga Tucker, Andrew D. Beggs, Philippe Tanière, Sonia Puig, Gianmarco Contino, Tim Underwood, Robert Walker, Ben Grace, Jesper Lagergren, James Gossage, Andrew Davies, Fuju Chang, Ula Mahadeva, Vicky Goh, Francesca D. Ciccarelli, Grant Sanders, Richard Berrisford, David Tsz Chung Chan, Ed Cheong, Bhaskar Kumar, L. Sreedharan, Simon L. Parsons, Irshad Soomro, Philip Kaye, John Saunders, Laurence Lovat, Rehan Haidry, Michael Scott, Sharmila Sothi, Suzy Lishman, George B. Hanna, Christopher J. Peters, Krishna Moorthy, Anna M. Grabowska, Richard Turkington, Damian McManus, Helen G. Coleman, Russell Petty, Freddie Bartlet, Ted R. Hupp, Javier A. Alfaro · 发表于：Molecular & Cellular Proteomics · 年份：2024 · DOI：10.1016/j.mcpro.2024.100764 · 被引用次数：12 · 研究领域：Cancer-related gene regulation、RNA modifications and cancer、Esophageal Cancer Research and Treatment

Efforts to address the poor prognosis associated with esophageal adenocarcinoma (EAC) have been hampered by a lack of biomarkers to identify early disease and therapeutic targets. Despite extensive efforts to understand the somatic mutations associated with EAC over the past decade, a gap remains in understanding how the atlas of genomic aberrations in this cancer impacts the proteome and which somatic variants are of importance for the disease phenotype. We performed a quantitative proteomic analysis of 23 EACs and matched adjacent normal esophageal and gastric tissues. We explored the correlation of transcript and protein abundance using tissue-matched RNA-seq and proteomic data from seven patients and further integrated these data with a cohort of EAC RNA-seq data (n = 264 patients), EAC whole-genome sequencing (n = 454 patients), and external published datasets. We quantified protein expression from 5879 genes in EAC and patient-matched normal tissues. Several biomarker candidates with EAC-selective expression were identified, including the transmembrane protein GPA33. We further verified the EAC-enriched expression of GPA33 in an external cohort of 115 patients and confirm this as an attractive diagnostic and therapeutic target. To further extend the insights gained from our proteomic data, an integrated analysis of protein and RNA expression in EAC and normal tissues revealed several genes with poorly correlated protein and RNA abundance, suggesting posttranscriptional ...