Adhesion molecule protein signature in ovarian cancer effusions is prognostic of patient outcome

Abstract

BACKGROUND: Ovarian cancer cells in malignant effusions lack attachment to solid-phase matrix substrata and receive survival stimuli through cell-cell and cell-soluble matrix molecule interactions. We hypothesized that adhesion-related survival and proliferation pathway signals can inform clinical outcomes and guide targeted therapeutics. METHODS: Lysed cell pellets from a blinded set of benign (n ¼ 20) and malignant (n ¼ 51) peritoneal and pleural ovarian cancer patient effusions were applied to reverse-phase protein arrays and examined using validated antibodies to adhesion-associated protein endpoints. Results were subjected to hierarchical clustering for signature development. Association between specimen type, protein expression, and clinicopathologic associations were analyzed using the Mann-Whitney U test. Survival outcomes were estimated using the Kaplan-Meier method with log-rank comparison. RESULTS: A cell adhesion protein signature obtained from unsupervised clustering distinguished malignant from benign effusions (P ¼ 6.18E-06). Protein subset analyses from malignant cases defined 3 cell adhesion protein clusters driven by E-cadherin, epithelial cell adhesion molecule, and N-cadherin, respectively. The components of the E-and N-cadherin clusters correlated with clinical outcome by Kaplan-Meier statistics. Univariate analysis indicated that FAK and phosphorylated AKT were associated with higher overall and progression-free survival (PFS) (P ¼ .03), and Akt, phosphorylated paxillin, and E-and N-cadherin were associated with improved PFS (P .05). If 4 or 5 of the index adhesion proteins were high, PFS was improved by multivariate analysis (P .01). CONCLUSIONS: This hypothesis-testing examination of tumor cell adhesion molecules and pathways yielded potential predictive biomarkers with which to triage patients to selected molecular therapeutics and may serve as a platform for biomarker-based stratification for clinical application.

Overexpression of Paxillin Correlates with Tumor Progression and Predicts Poor Survival in Glioblastoma

“…Consistently, in this study, we found that PXN expression was positively correlated with tumor grade in mRNA profiling of four independent datasets, as well as PXN protein expression difference which was measured by IHC from an independent validation set of samples. The above results indicate both PXN RNA and protein were associated with tumor malignancy, which has been reported in other cancers .…”

Migfilin, α-parvin and β-parvin are differentially expressed in ovarian serous carcinoma effusions, primary tumors and solid metastases

“…In view of the role of the studied proteins in adhesion and intracellular signaling, we investigated their potential association with markers related to these processes that have been previously studied in our effusion material, including proteins analyzed by proteomics (cadherin, FAK, paxillin, pyk, EpCAM, p-ERK, p-AKT) [29], PINCH-2 by flow cytometry [21] and proteins analyzed using IHC, including claudin-1, -3, -4 and -7 [30], the anti-apoptotic proteins XIAP and Survivin [31], p-AKT and p-mTOR [32], and NFkB-p65 [33]. α-parvin was excluded from this analysis in view of its almost universal absence from OC effusions.…”

Pre-analytical issues in effusion cytology

“…Studies of effusion specimens applying proteomics used fresh samples, as well as samples frozen at -20°C or -80°C [89][90][91][92][93].…”