A multi‐omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma. Issue 9 (26th September 2021)

• Record Type: Journal Article
• Authors: Jin, Xing; Liu, Lei; Wu, Jia; Jin, Xiaoxia; Yu, Guanzhen; Jia, Lijun; Wang, Fengying; Shi, Minxin; Lu, Haimin; Liu, Jibin; Liu, Dan; Yang, Jing; Li, Hua; Ni, Yan; Luo, Qin; Jia, Wei; Wang, Wei; Chen, Wen‐Lian
• Is Part Of: Clinical and translational medicine. Volume 11:Issue 9(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-09-26
• Subjects: esophageal squamous cell carcinoma -- fibrillarin -- molecular feature -- multi‐omics; Clinical medicine -- Periodicals; Medicine, Experimental -- Periodicals; Medical innovations -- Periodicals; Molecular biology -- Periodicals; Pathology, Molecular -- Periodicals; 616.027
• DOI: 10.1002/ctm2.538
• Languages: English
• ISSNs: 2001-1326

Abstract

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. Abstract : 1. A new molecular feature of ESCC that involves both active posttranscriptional and posttranslational regulation was unveiled. 2. ESCC‐related signaling and metabolic pathways, networks among omics data, and common cancer/testis antigens along with established cancer drivers and kinases were delineated. 3. Proteins with close linkage to ESCC prognosis were discovered, and a new prognostic protein, fibrillarin (FBL), was further validated, functionally studied, and found to correlate negatively with patient outcomes.