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Updated: Jan 11, 2026
Development of Compendium for Esophageal Squamous Cell Carcinoma
Published on: April 12, 2024
SH3BGRL2 as a vital tumor suppressor and prognostic factor in human esophageal squamous cell carcinoma
Kaiyan Chen1,2, Rui Zhu3, Fanrong Zhang4
1Laboratory of Cancer Biology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Background:
Esophageal squamous cell carcinoma (ESCC), a highly aggressive malignancy associated with dismal prognosis, is a global healthcare threat. The molecular mechanisms underlying the carcinogenesis and progression of ESCC remain to be elucidated. This study aims to systematically dissect the pivotal genes and molecular mechanisms that orchestrate the progression of ESCC.
Methods:
RNA-sequencing was performed to identify differentially expressed genes between resected ESCC tumor samples and paired adjacent normal tissues. The protein expression levels of SH3 domain binding glutamate rich protein-like 2 (SH3BGRL2) were assessed via immunohistochemistry (IHC) staining in a tissue microarray of 247 cases of ESCC tumor samples and paired normal tissues. Subsequent in vitro and in vivo assays were conducted to identify the functional role of SH3BGRL2 in ESCC.
Results:
RNA-sequencing and IHC analyses both revealed significant downregulation of SH3BGRL2 in ESCC tissues (P<0.01). Patients with higher SH3BGRL2 expression exhibited significantly longer disease-free survival (DFS) and overall survival (OS) (DFS: 47.1 vs. 18.2 months, P=0.020; OS: 60.8 vs. 20.6 months, P=0.003). Moreover, SH3BGRL2 was identified as an independent prognostic factor for patients with resected ESCC in terms of DFS [hazard ratio (HR) =0.62, 95% confidence interval (CI): 0.43-0.91; P=0.02] and OS (HR =0.55, 95% CI: 0.37-0.81; P=0.002). In terms of mechanism, the proliferative capacity of ESCC patient-derived cell lines (PDCs) and in vivo xenograft models was enhanced upon SH3BGRL2 knockdown (P<0.05). Moreover, overexpression of SH3BGRL2 significantly inhibited cell proliferation. Notably, early growth response 1 (EGR1) expression was elevated in SH3BGRL2-silenced PDCs, suggesting that SH3BGRL2 may suppress ESCC proliferation by blocking the EGR1 pathway.
Conclusions:
SH3BGRL2 acts as a key tumor suppressor and prognostic determinant in ESCC, which represents a novel insight into the pathogenesis of this malignancy.
Insights
SH3BGRL2 is downregulated in esophageal squamous cell carcinoma (ESCC), acting as a tumor suppressor. Higher SH3BGRL2 expression correlates with better survival, offering new insights into ESCC pathogenesis.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Esophageal squamous cell carcinoma (ESCC) is an aggressive cancer with poor prognosis.
- The molecular drivers of ESCC carcinogenesis and progression require further elucidation.
- Understanding ESCC's molecular mechanisms is crucial for developing targeted therapies.
Purpose of the Study:
- To identify key genes and molecular mechanisms driving ESCC progression.
- To investigate the role of SH3BGRL2 in ESCC development and patient outcomes.
- To explore the potential of SH3BGRL2 as a prognostic biomarker for ESCC.
Main Methods:
- RNA-sequencing to identify differentially expressed genes in ESCC tumors versus normal tissues.
- Immunohistochemistry (IHC) to assess SH3BGRL2 protein expression in 247 ESCC samples.
- In vitro and in vivo assays to determine the functional significance of SH3BGRL2 in ESCC.
Main Results:
- SH3BGRL2 was significantly downregulated in ESCC tissues at both RNA and protein levels.
- Increased SH3BGRL2 expression was associated with longer disease-free survival (DFS) and overall survival (OS).
- SH3BGRL2 acts as an independent prognostic factor for ESCC patients, suppressing proliferation possibly via the EGR1 pathway.
Conclusions:
- SH3BGRL2 functions as a critical tumor suppressor in ESCC.
- SH3BGRL2 serves as a significant prognostic determinant for ESCC patients.
- This study provides novel insights into ESCC pathogenesis and identifies a potential therapeutic target.
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