ADAM17 is associated with EMMPRIN and predicts poor prognosis in patients with uterine cervical carcinoma
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Published on: September 15, 2023
Qin Xu1, Mingang Ying, Guilin Chen
1Department of Gynecology, Fujian Provincial Cancer Hospital, Fuzhou, China.
Abstract:
Metalloproteinase activities of a disintegrin and metalloproteinase 17 (ADAM17), amphiregulin (AREG), extracellular matrix metalloproteinase inducer (EMMPRIN), and matrix metalloproteinases (MMPs) are involved in tumor biology. In patients with uterine cervical carcinoma, the expression and prognostic significance of ADAM17 remain to be fully elucidated. The expression of ADAM17, AREG, EMMPRIN, phospho-epidermal growth factor receptor (p-EGFR), phospho-extracellular signal-regulated kinase (p-ERK), MMP-2, and MMP-9 was assessed by immunohistochemistry and/or Western blotting from cervical carcinoma cell lines, SiHa and HeLa cells, and cervical carcinoma tissues. AREG activity was measured by ELISA assay. The correlation of ADAM17, AREG, EMMPRIN, and MMP-9 expression with patients' survival rates was assessed by Kaplan-Meier and Cox regression analyses. RNA interference (RNAi) experiment was performed using small interfering mRNA to ADAM17 and EMMPRIN. ADAM17, EMMPRIN, and MMP-9 protein content was overexpressed in cervical carcinoma tissues compared with normal cervical tissues (P < 0.05). Strong expression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly associated with stages, lymph node metastasis, differentiation, and parametrium invasion (P < 0.05). Overexpression of ADAM17, AREG, EMMPRIN, and MMP-9 was significantly correlated with short progression-free survival and overall survival (P < 0.05). Multivariate analysis suggested that lymph node metastasis, parametrium invasion, and ADAM17 expression were independent prognostic indicators for cervical cancer. ADAM17 RNAi decreased EMMPRIN, p-EGFR, p-ERK, MMP-2, and MMP-9 proteins in SiHa and HeLa cells. ELISA assay revealed that AREG activity was stimulated by ADAM17 and was reversed by ADAM17 RNAi in SiHa and HeLa cells. Our data suggest that the increased expression of ADAM17 in cervical cancer is significantly associated with aggressive progression and poor prognosis. ADAM17 may be a molecular marker for predicting the progression and prognosis in cervical cancer.
Insights
Metalloproteinase ADAM17 is overexpressed in cervical cancer, correlating with aggressive disease and poor survival. Targeting ADAM17 may offer a new strategy for predicting and treating uterine cervical carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) and their regulators are implicated in tumor progression.
- The role of ADAM17 (a disintegrin and metalloproteinase 17) in uterine cervical carcinoma remains unclear.
Purpose of the Study:
- To investigate the expression and prognostic significance of ADAM17 in cervical cancer.
- To explore the relationship between ADAM17, amphiregulin (AREG), EMMPRIN, and MMPs in cervical cancer progression.
Main Methods:
- Immunohistochemistry and Western blotting were used to assess protein expression in cell lines and tissues.
- ELISA measured AREG activity.
- Kaplan-Meier and Cox regression analyses evaluated survival correlations.
- RNA interference (RNAi) was employed to study ADAM17 function.
Main Results:
- ADAM17, EMMPRIN, and MMP-9 were overexpressed in cervical cancer tissues compared to normal tissues.
- High expression of ADAM17, AREG, EMMPRIN, and MMP-9 correlated with advanced stage, metastasis, and poor differentiation.
- ADAM17 overexpression was linked to shorter progression-free and overall survival.
- ADAM17 knockdown reduced EMMPRIN, p-EGFR, p-ERK, MMP-2, and MMP-9 levels and inhibited AREG activity.
Conclusions:
- Increased ADAM17 expression is associated with aggressive cervical cancer progression and poor prognosis.
- ADAM17 may serve as a valuable molecular marker for predicting cervical cancer outcomes.
- ADAM17 influences AREG activity and downstream signaling pathways involved in tumor growth.
