A multi‐omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma

Abstract Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with inferior prognosis. Here, we conducted comprehensive transcriptomic, proteomic, phosphoproteomic, and metabolomic characterization of human, treatment‐naive ESCC and paired normal adjacent ti...

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Autores principales:	Xing Jin, Lei Liu, Jia Wu, Xiaoxia Jin, Guanzhen Yu, Lijun Jia, Fengying Wang, Minxin Shi, Haimin Lu, Jibin Liu, Dan Liu, Jing Yang, Hua Li, Yan Ni, Qin Luo, Wei Jia, Wei Wang, Wen‐Lian Chen
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	esophageal squamous cell carcinoma fibrillarin molecular feature multi‐omics Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/d4da7c46e67d4a49ab9510b0e178d250
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spelling	oai:doaj.org-article:d4da7c46e67d4a49ab9510b0e178d2502021-11-11T12:06:39ZA multi‐omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma2001-132610.1002/ctm2.538https://doaj.org/article/d4da7c46e67d4a49ab9510b0e178d2502021-09-01T00:00:00Zhttps://doi.org/10.1002/ctm2.538https://doaj.org/toc/2001-1326Abstract Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with inferior prognosis. Here, we conducted comprehensive transcriptomic, proteomic, phosphoproteomic, and metabolomic characterization of human, treatment‐naive ESCC and paired normal adjacent tissues (cohort 1, n = 24) in an effort to identify new molecular vulnerabilities for ESCC and potential therapeutic targets. Integrative analysis revealed a small group of genes that were related to the active posttranscriptional and posttranslational regulation of ESCC. By using proteomic, phosphoproteomic, and metabolomic data, networks of ESCC‐related signaling and metabolic pathways that were closely linked to cancer etiology were unraveled. Notably, integrative analysis of proteomic and phosphoproteomic data pinpointed that certain pathways involved in RNA transcription, processing, and metabolism were stimulated in ESCC. Importantly, proteins with close linkage to ESCC prognosis were identified. By enrolling an ESCC patient cohort 2 (n = 41), three top‐ranked prognostic proteins X‐prolyl aminopeptidase 3 (XPNPEP3), bromodomain PHD finger transcription factor (BPTF), and fibrillarin (FBL) were verified to have increased expression in ESCC. Among these prognostic proteins, only FBL, a well‐known nucleolar methyltransferase, was essential for ESCC cell growth in vitro and in vivo. Furthermore, a validation study using an ESCC patient cohort 3 (n = 100) demonstrated that high FBL expression predicted unfavorable patient survival. Finally, common cancer/testis antigens and established cancer drivers and kinases, all of which could direct therapeutic decisions, were characterized. Collectively, our multi‐omics analyses delineated new molecular features associated with ESCC pathobiology involving epigenetic, posttranscriptional, posttranslational, and metabolic characteristics, and unveiled new molecular vulnerabilities with therapeutic potential for ESCC.Xing JinLei LiuJia WuXiaoxia JinGuanzhen YuLijun JiaFengying WangMinxin ShiHaimin LuJibin LiuDan LiuJing YangHua LiYan NiQin LuoWei JiaWei WangWen‐Lian ChenWileyarticleesophageal squamous cell carcinomafibrillarinmolecular featuremulti‐omicsMedicine (General)R5-920ENClinical and Translational Medicine, Vol 11, Iss 9, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	esophageal squamous cell carcinoma fibrillarin molecular feature multi‐omics Medicine (General) R5-920
spellingShingle	esophageal squamous cell carcinoma fibrillarin molecular feature multi‐omics Medicine (General) R5-920 Xing Jin Lei Liu Jia Wu Xiaoxia Jin Guanzhen Yu Lijun Jia Fengying Wang Minxin Shi Haimin Lu Jibin Liu Dan Liu Jing Yang Hua Li Yan Ni Qin Luo Wei Jia Wei Wang Wen‐Lian Chen A multi‐omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma
description	Abstract Esophageal squamous cell carcinoma (ESCC) is a major histological subtype of esophageal cancer with inferior prognosis. Here, we conducted comprehensive transcriptomic, proteomic, phosphoproteomic, and metabolomic characterization of human, treatment‐naive ESCC and paired normal adjacent tissues (cohort 1, n = 24) in an effort to identify new molecular vulnerabilities for ESCC and potential therapeutic targets. Integrative analysis revealed a small group of genes that were related to the active posttranscriptional and posttranslational regulation of ESCC. By using proteomic, phosphoproteomic, and metabolomic data, networks of ESCC‐related signaling and metabolic pathways that were closely linked to cancer etiology were unraveled. Notably, integrative analysis of proteomic and phosphoproteomic data pinpointed that certain pathways involved in RNA transcription, processing, and metabolism were stimulated in ESCC. Importantly, proteins with close linkage to ESCC prognosis were identified. By enrolling an ESCC patient cohort 2 (n = 41), three top‐ranked prognostic proteins X‐prolyl aminopeptidase 3 (XPNPEP3), bromodomain PHD finger transcription factor (BPTF), and fibrillarin (FBL) were verified to have increased expression in ESCC. Among these prognostic proteins, only FBL, a well‐known nucleolar methyltransferase, was essential for ESCC cell growth in vitro and in vivo. Furthermore, a validation study using an ESCC patient cohort 3 (n = 100) demonstrated that high FBL expression predicted unfavorable patient survival. Finally, common cancer/testis antigens and established cancer drivers and kinases, all of which could direct therapeutic decisions, were characterized. Collectively, our multi‐omics analyses delineated new molecular features associated with ESCC pathobiology involving epigenetic, posttranscriptional, posttranslational, and metabolic characteristics, and unveiled new molecular vulnerabilities with therapeutic potential for ESCC.
format	article
author	Xing Jin Lei Liu Jia Wu Xiaoxia Jin Guanzhen Yu Lijun Jia Fengying Wang Minxin Shi Haimin Lu Jibin Liu Dan Liu Jing Yang Hua Li Yan Ni Qin Luo Wei Jia Wei Wang Wen‐Lian Chen
author_facet	Xing Jin Lei Liu Jia Wu Xiaoxia Jin Guanzhen Yu Lijun Jia Fengying Wang Minxin Shi Haimin Lu Jibin Liu Dan Liu Jing Yang Hua Li Yan Ni Qin Luo Wei Jia Wei Wang Wen‐Lian Chen
author_sort	Xing Jin
title	A multi‐omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma
title_short	A multi‐omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma
title_full	A multi‐omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma
title_fullStr	A multi‐omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma
title_full_unstemmed	A multi‐omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma
title_sort	multi‐omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/d4da7c46e67d4a49ab9510b0e178d250
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A multi‐omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma

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