Novel prognostic marker TGFBI affects the migration and invasion function of ovarian cancer cells and activates the integrin αvβ3-PI3K-Akt signaling pathway
© 2024. The Author(s)..
BACKGROUND: Individual patients with ovarian cancer show remarkably different prognosis. Present prognostic models for ovarian cancer mainly focus on clinico-pathological parameters, so quantifiable prognostic markers at molecular level are urgently needed. Platelets contribute to ovarian cancer progression, but have not been considered as biomarkers likely due to their instability. Here, we aimed to search for a stable prognostic marker from platelet-treated ovarian cancer cells, and explore its functions and mechanisms.
METHODS: Microarrays analysis was done with platelet-treated SKOV-3 ovarian cancer cells. Relevant studies were searched in the Gene Expression Omnibus (GEO) database. The candidate genes were determined by differentially expressed genes (DEGs), Venn diagram drawing, protein-protein interaction (PPI) network, Cox proportional hazards model and Kaplan-Meier analysis. The expression of TGFBI in clinical samples was assessed by immunehistochemical staining (IHC), and the association of TGFBI levels with the clinic-pathological characteristics and prognosis in ovarian cancer patients was evaluated by univariate and multivariate analysis. The functions of TGFBI were predicted using data from TCGA, and validated by in vitro and in vivo experiments. The mechanism exploration was performed based on proteomic analysis, molecular docking and intervention study.
RESULTS: TGFBI was significantly higher expressed in the platelet-treated ovarian cancer cells. An analysis of bioinformatics data revealed that increased expression of TGFBI led to significant decrease of overall survival (OS), progression-free survival (PFS) and post-progression survival (PPS) in ovarian cancer patients. Tissue microarray results showed that TGFBI was an independent factor for ovarian cancer, and TGFBI expression predict poor prognosis. Functionally, TGFBI affected the migration and invasion of ovarian cancer cells by regulation of epithelial mesenchymal transition (EMT) markers (CDH1 and CDH2) and extracellular matrix (ECM) degradation proteins (MMP-2). Mechanistically, TGFBI phosphorylated PI3K and Akt by combining integrin αvβ3.
CONCLUSIONS: We found out TGFBI as a novel prognostic indicator for ovarian cancer patients. TGFBI could promote metastasis in ovarian cancer by EMT induction and ECM remodeling, which might be associated with the activation of integrin αvβ3-PI3K-Akt signaling pathway.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
|---|---|
| Enthalten in: |
Journal of ovarian research - 17(2024), 1 vom: 23. Feb., Seite 50 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Wang, Hao [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 26.02.2024 Date Revised 08.03.2024 published: Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1186/s13048-024-01377-5 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM368858901 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM368858901 | ||
| 003 | DE-627 | ||
| 005 | 20240308232618.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240229s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1186/s13048-024-01377-5 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1320.xml |
| 035 | |a (DE-627)NLM368858901 | ||
| 035 | |a (NLM)38395907 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Wang, Hao |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Novel prognostic marker TGFBI affects the migration and invasion function of ovarian cancer cells and activates the integrin αvβ3-PI3K-Akt signaling pathway |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 26.02.2024 | ||
| 500 | |a Date Revised 08.03.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a BACKGROUND: Individual patients with ovarian cancer show remarkably different prognosis. Present prognostic models for ovarian cancer mainly focus on clinico-pathological parameters, so quantifiable prognostic markers at molecular level are urgently needed. Platelets contribute to ovarian cancer progression, but have not been considered as biomarkers likely due to their instability. Here, we aimed to search for a stable prognostic marker from platelet-treated ovarian cancer cells, and explore its functions and mechanisms | ||
| 520 | |a METHODS: Microarrays analysis was done with platelet-treated SKOV-3 ovarian cancer cells. Relevant studies were searched in the Gene Expression Omnibus (GEO) database. The candidate genes were determined by differentially expressed genes (DEGs), Venn diagram drawing, protein-protein interaction (PPI) network, Cox proportional hazards model and Kaplan-Meier analysis. The expression of TGFBI in clinical samples was assessed by immunehistochemical staining (IHC), and the association of TGFBI levels with the clinic-pathological characteristics and prognosis in ovarian cancer patients was evaluated by univariate and multivariate analysis. The functions of TGFBI were predicted using data from TCGA, and validated by in vitro and in vivo experiments. The mechanism exploration was performed based on proteomic analysis, molecular docking and intervention study | ||
| 520 | |a RESULTS: TGFBI was significantly higher expressed in the platelet-treated ovarian cancer cells. An analysis of bioinformatics data revealed that increased expression of TGFBI led to significant decrease of overall survival (OS), progression-free survival (PFS) and post-progression survival (PPS) in ovarian cancer patients. Tissue microarray results showed that TGFBI was an independent factor for ovarian cancer, and TGFBI expression predict poor prognosis. Functionally, TGFBI affected the migration and invasion of ovarian cancer cells by regulation of epithelial mesenchymal transition (EMT) markers (CDH1 and CDH2) and extracellular matrix (ECM) degradation proteins (MMP-2). Mechanistically, TGFBI phosphorylated PI3K and Akt by combining integrin αvβ3 | ||
| 520 | |a CONCLUSIONS: We found out TGFBI as a novel prognostic indicator for ovarian cancer patients. TGFBI could promote metastasis in ovarian cancer by EMT induction and ECM remodeling, which might be associated with the activation of integrin αvβ3-PI3K-Akt signaling pathway | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Integrin αvβ3 | |
| 650 | 4 | |a Invasion | |
| 650 | 4 | |a Metastasis | |
| 650 | 4 | |a Migration | |
| 650 | 4 | |a Ovarian cancer | |
| 650 | 4 | |a PI3K-Akt signaling pathway | |
| 650 | 4 | |a Prognosis | |
| 650 | 4 | |a TGFBI | |
| 650 | 7 | |a betaIG-H3 protein |2 NLM | |
| 650 | 7 | |a 148710-76-3 |2 NLM | |
| 650 | 7 | |a Extracellular Matrix Proteins |2 NLM | |
| 650 | 7 | |a Integrin alphaVbeta3 |2 NLM | |
| 650 | 7 | |a Phosphatidylinositol 3-Kinases |2 NLM | |
| 650 | 7 | |a EC 2.7.1.- |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-akt |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Transforming Growth Factor beta |2 NLM | |
| 700 | 1 | |a Xu, Yin-Hai |e verfasserin |4 aut | |
| 700 | 1 | |a Guo, Yi |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of ovarian research |d 2008 |g 17(2024), 1 vom: 23. Feb., Seite 50 |w (DE-627)NLM184542146 |x 1757-2215 |7 nnns |
| 773 | 1 | 8 | |g volume:17 |g year:2024 |g number:1 |g day:23 |g month:02 |g pages:50 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1186/s13048-024-01377-5 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 17 |j 2024 |e 1 |b 23 |c 02 |h 50 | ||