Related Experiment Video
Updated: Oct 18, 2025
Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
A multi-omics study delineates new molecular features and therapeutic targets for esophageal squamous cell carcinoma
1Cancer Institute, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
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.
Insights
This study identifies Fibrillarin (FBL) as a key protein essential for esophageal squamous cell carcinoma (ESCC) growth and survival. High FBL expression in ESCC patients indicates a poorer prognosis, highlighting FBL as a potential therapeutic target for this cancer.
Area of Science:
- Oncology
- Molecular Biology
- Genomics
Background:
- Esophageal squamous cell carcinoma (ESCC) presents a significant clinical challenge due to its poor prognosis.
- Identifying novel molecular vulnerabilities is crucial for developing effective ESCC therapies.
Purpose of the Study:
- To comprehensively characterize the molecular landscape of treatment-naive ESCC using multi-omics approaches.
- To identify new molecular vulnerabilities and potential therapeutic targets for ESCC.
Main Methods:
- Integrated analysis of transcriptomic, proteomic, phosphoproteomic, and metabolomic data from human ESCC and adjacent normal tissues.
- Verification of prognostic proteins in independent ESCC patient cohorts.
- In vitro and in vivo functional studies of identified key proteins.
Main Results:
- Multi-omics integration revealed dysregulated RNA processing and metabolism pathways in ESCC.
- Three prognostic proteins, XPNPEP3, BPTF, and FBL, were identified with increased expression in ESCC.
- Fibrillarin (FBL) was essential for ESCC cell growth and high FBL expression correlated with unfavorable patient survival.
Conclusions:
- Multi-omics analysis delineated novel molecular features of ESCC pathobiology.
- Fibrillarin (FBL) is a critical driver of ESCC progression and a promising therapeutic target.
