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Expression of SPRED2 in the lung adenocarcinoma
Yoko Ota1, Tong Gao1, Masayoshi Fujisawa1
1Department of Pathology and Experimental Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama 700-8558, Japan.
Abstract:
SPRED2 (Sprouty-related, EVH1 domain-containing protein 2), a negative regulator of the ERK1/2 pathway, is downregulated in several cancers; however, the significance of SPRED2 expression in lung adenocarcinoma (LUAD) remains unclear. Here, we investigated the pathological expression of SPRED2 and its relationship with ERK1/2 activation (ERK1/2 phosphorylation), Ki67 index and clinicopathological features in 77 LUAD tissues from clinical patients. Immunohistochemically, SPRED2 expression was decreased in invasive adenocarcinoma (IA) compared to adenocarcinoma in situ (AIS). There was a negative correlation between SPRED2 expression and pERK1/2 levels and a positive correlation between SPRED2 expression and Ki67 index. In the database analysis, the survival probability was higher in patients with higher SPRED2 expression than in those with lower expression. In vitro, SPRED2 deletion increased cell proliferation, migration and invasion of three LUAD cell lines (A549:KRAS mutation, H1993:METamplification, and HCC4006:EGFR mutation), whereas SPRED2 overexpression decreased these responses. Thus, SPRED2 appears to be a regulator of LUAD progression and a potential target for the treatment of LUAD.
Insights
Sprouty-related, EVH1 domain-containing protein 2 (SPRED2) is downregulated in lung adenocarcinoma (LUAD), correlating with increased tumor progression and poorer survival. SPRED2 warrants further investigation as a potential therapeutic target for LUAD.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Sprouty-related, EVH1 domain-containing protein 2 (SPRED2) negatively regulates the ERK1/2 pathway and is often downregulated in various cancers.
- The specific role and clinical significance of SPRED2 in lung adenocarcinoma (LUAD) pathogenesis remain largely undetermined.
Purpose of the Study:
- To investigate the expression patterns of SPRED2 in LUAD tissues.
- To determine the correlation between SPRED2 expression, ERK1/2 pathway activation, cell proliferation markers, and clinicopathological features in LUAD patients.
- To evaluate the functional impact of SPRED2 on LUAD cell behavior in vitro.
Main Methods:
- Immunohistochemical analysis of SPRED2 expression in 77 LUAD tissues.
- Assessment of ERK1/2 phosphorylation (pERK1/2) and Ki67 index.
- In vitro studies involving SPRED2 deletion and overexpression in LUAD cell lines (A549, H1993, HCC4006).
Main Results:
- SPRED2 expression was significantly decreased in invasive adenocarcinoma compared to adenocarcinoma in situ.
- A negative correlation was observed between SPRED2 levels and pERK1/2, and a positive correlation with the Ki67 index.
- Database analysis indicated higher survival probability in patients with elevated SPRED2 expression.
- In vitro, SPRED2 deletion enhanced LUAD cell proliferation, migration, and invasion, while SPRED2 overexpression suppressed these processes.
Conclusions:
- SPRED2 functions as a tumor suppressor in LUAD by inhibiting cell proliferation, migration, and invasion.
- Reduced SPRED2 expression is associated with increased tumor aggressiveness and poorer patient outcomes.
- SPRED2 represents a promising therapeutic target for the treatment of lung adenocarcinoma.
