Adhesion molecule protein signature in ovarian cancer effusions is prognostic of patient outcome.
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 = 20) and malignant (n = 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 = 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 = .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.
Molecular Signaling Section, Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA.
Geoffrey
G
Kim
Ben
B
Davidson
Ryan
R
Henning
Junbai
J
Wang
Minshu
M
Yu
Christina
C
Annunziata
Thea
T
Hetland
Elise C
EC
Kohn
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001202:Ascitic Fluid / Q000737:chemistry*; D015815:Cell Adhesion Molecules / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D010996:Pleural Effusion / Q000378:metabolism*; D011379:Prognosis
D015815:Cell Adhesion Molecules