Protease inhibitor SERPINA1 expression in epithelial ovarian cancer

Normandin, Karine; Péant, Benjamin; Page, Cécile Le; Ladurantaye, Manon de; Ouellet, Véronique; Tonin, Patricia N.; Provencher, Diane; Mes-Masson, Anne-Marie

doi:10.1007/s10585-009-9303-6

Cited by 35 publications

(28 citation statements)

References 63 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings suggest that serpinA1 affects the incidence and progression of gastric cancer by promoting the mobility and metastasis of cancer cells. Our results are in concordance with other studies, which reported that serpinA1 has a role in tumour progression (Tahara et al , 1984; Karashima et al , 1990; Higashiyama et al , 1992; Allgayer et al , 1998; de Sá et al , 2007; Normandin et al , 2010; Farshchian et al , 2011). …”

Section: Discussionsupporting

confidence: 94%

Serpin peptidase inhibitor clade A member 1 is a biomarker of poor prognosis in gastric cancer

et al. 2014

View full text Add to dashboard Cite

Background:In a previous study, we reported that serpin peptidase inhibitor clade A member 1 (serpinA1) is upregulated in Snail-overexpressing gastric cancer. Although serpinA1 has been studied in several types of cancer, little is known about its roles and mechanisms of action. In this study, we examined the role of serpinA1 in the migration and invasion of gastric cancers and determined its underlying mechanism.Methods:Expression levels were assessed by western blot analyses and real-time PCR. Snail binding to serpinA1 promoter was analysed by chromatin immunoprecipitation (ChIP) assays. The roles of serpinA1 were studied using cell invasion and migration assays. In addition, the clinicopathologic and prognostic significance of serpinA1 expression were validated in 400 gastric cancer patients using immunohistochemical analysis.Results:Overexpression of Snail resulted in upregulation of serpinA1 in gastric cancer cell lines, AGS and MKN45, whereas knockdown of Snail inhibited serpinA1 expression. Chromatin immunoprecipitation analysis showed that overexpression of Snail increased Snail recruitment to the serpinA1 promoter. Overexpression of serpinA1 increased the migration and invasion of gastric cancer cells, whereas knockdown of serpinA1 decreased invasion and migration. Moreover, serpinA1 increased mRNA levels and release of metalloproteinase-8 in gastric cancer cells. Serpin peptidase inhibitor clade A member 1 was observed in the cytoplasm of tumour cells and the stroma by immunohistochemistry. Enhanced serpinA1 expression was significantly associated with increased tumour size, advanced T stage, perineural invasion, lymphovascular invasion, lymph node metastases, and shorter overall survival.Conclusions:Serpin peptidase inhibitor clade A member 1 induces the invasion and migration of gastric cancer cells and its expression is associated with the progression of gastric cancer. These results may provide a potential target to prevent invasion and metastasis in gastric cancer.

show abstract

Section: Discussionsupporting

confidence: 94%

Serpin peptidase inhibitor clade A member 1 is a biomarker of poor prognosis in gastric cancer

et al. 2014

View full text Add to dashboard Cite

show abstract

“…SERPINA1 shows one of the largest fold increases (3.8-fold increased) in protein expression level in PTR cohort compared with PTS cohort (p<0.05). Nevertheless, our data are in good agreement with prior studies elicited above, but disagree with the results of Normandin et al (7).…”

Section: Discussionsupporting

confidence: 76%

Identification of proteomic and metabolic signatures associated with chemoresistance of human epithelial ovarian cancer

Wang

Yin

et al. 2016

International Journal of Oncology

View full text Add to dashboard Cite

Abstract. Emerging drug resistance in epithelial ovarian cancer (EOC) thwarted progress in platinum-based chemotherapy, resulting in increased mortality, morbidity and healthcare costs. The aim of this study was to detect the responses induced by chemotherapy at protein and metabolite levels, and to search for new plasma markers that can predict resistance to platinum-based chemotherapy in EOC patients, leading to improved clinical response rates. Serum samples were collected and subjected to proteomic relative quantitation analysis and metabolomic analysis. Differentially expressed proteins and metabolites were subjected to bioinformatics and statistical analysis. Proteins that played a key role in platinum resistance were validated by western blotting and enzyme-linked immunosorbent assay (ELISA). Metabolites that were the main contributors to the groups and closely with clinical characteristics were identified based on the database using nuclear magnetic resonance (NMR). In total, 248 proteins from two independent experiments were identified using isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic approach. Among them, FN1, SERPINA1, GPX3 and ORM1 were chosen for western blotting and ELISA validation. Platinum resistance likely associated with differentially expressed proteins and FN1, SERPINA1 and ORM1 may play a positive role in chemotherapy. HPLC-MS analysis of four groups revealed a total of 25,800 metabolic features, of which six compounds were chosen for candidate biomarkers and identified based on the database using NMR. The metabolic signatures of normal control (NC), platinum-sensitive (PTS) and platinum-resistant (PTR) groups were clearly separated from each other.Those findings may provide theoretical clues for the prediction of chemotherapeutic response and reverse of drug resistance, even lead to novel targets for therapeutic intervention.

show abstract

“…In the oncology literature reports describe genetic aberrations in cancer, 22 increased levels in the serum of patients with cancer 23 and a survival disadvantage for tumors expressing A1AT. 24 Previously, we reported that A1AT has 74% sensitivity and 80% specificity, 9 which are slightly decreased from current findings (87% and 84%, respectively). We believe that this difference is due to 1) different ELISA kits used to detect A1AT and 2) different statistical analyses.…”

Section: Discussioncontrasting

confidence: 65%

Diagnostic Potential of Urinary α1-Antitrypsin and Apolipoprotein E in the Detection of Bladder Cancer

Urquidi¹,

Goodison²,

Ross³

et al. 2012

Journal of Urology

View full text Add to dashboard Cite

Purpose The ability to reliably diagnose bladder cancer in voided urine samples would be a major advance. Using high throughput technologies, we identified a panel of bladder cancer associated biomarkers with potential clinical usefulness. In this study we tested 4 potential biomarkers for the noninvasive detection of bladder cancer. Materials and Methods We examined voided urine specimens from 124 patients, including 63 newly diagnosed with bladder cancer and 61 controls. Concentrations of proteins were assessed by enzyme-linked immunosorbent assay, including α1-antitrypsin, apolipoprotein E, osteopontin and pentraxin 3. Data were compared to the results of urinary cytology and the BTA Trak® enzyme-linked immunosorbent assay based bladder cancer detection assay. We used the AUC of ROC curves to compare the usefulness of each biomarker to detect bladder cancer. Results Urinary levels of α1-antitrypsin, apolipoprotein E and bladder tumor antigen were significantly increased in subjects with bladder cancer. α1-Antitrypsin (AUC 0.9087, 95% CI 0.8555–0.9619) and apolipoprotein E (AUC 0.8987, 95% CI 0.8449–0.9525) were the most accurate biomarkers. The combination of α1-antitrypsin and apolipoprotein E (AUC 0.9399) achieved 91% sensitivity, 89% specificity, and a positive and negative predictive value of 89% and 90%, respectively. Multivariate regression analysis highlighted only apolipoprotein E as an independent predictor of bladder cancer (OR 24.9, 95% CI 4.22–146.7, p = 0.0004). Conclusions Alone or in combination, α1-antitrypsin and apolipoprotein E show promise for the noninvasive detection of bladder cancer (OR 24.9, 95% CI 4.22– 146.7, p = 0.0004). Larger, prospective studies including more low grade, low stage tumors are needed to confirm these results.

show abstract

Protease inhibitor SERPINA1 expression in epithelial ovarian cancer

Cited by 35 publications

References 63 publications

Serpin peptidase inhibitor clade A member 1 is a biomarker of poor prognosis in gastric cancer

Serpin peptidase inhibitor clade A member 1 is a biomarker of poor prognosis in gastric cancer

Identification of proteomic and metabolic signatures associated with chemoresistance of human epithelial ovarian cancer

Diagnostic Potential of Urinary α1-Antitrypsin and Apolipoprotein E in the Detection of Bladder Cancer

Contact Info

Product

Resources

About