Changes in focal adhesion protein Talin-1 expression during malignant transformation leading to ovarian high-grade serous carcinoma.

Abstract

e17586 Background: Ovarian high-grade serous carcinoma (HGSC), the most lethal form of ovarian cancer, is often detected at late stages due to the lack of an early detection test resulting in low 5-year survival rates. Information on factors associated with malignant transformation and early metastasis is critical in developing interventional strategies to reduce the incidence and death due to HGSC. Talin-1, a focal adhesion protein, regulates cell–cell adhesion, and induces cytoskeletal remodeling leading to tumor cell migration and adhesion. Destabilization of the cell membrane during malignant development may shed Talin-1 in circulation which may be a potential early marker of progression of HGSC. Objective: The goal of this study was to examine the changes in Talin-1 expression during malignant transformation in ovaries and fimbria of the fallopian tube and its prevalence in serum. Difficulty in accessing patients with early-stage HGSC is a significant barrier to study malignant transformation and progression. Laying hen model of spontaneous ovarian HGSC was used together with clinical specimens. Methods: Two experiments were conducted. Exploratory study:Archived normal ovaries (n = 10), ovaries with HGSC at early (n = 10) and late (n = 10) stages from patients and their serum samples were used. Prospective study: Laying hens with no detectable abnormalities were selected and monitored using transvaginal ultrasound (TVUS) imaging at 10 week intervals for 10 months and sera were collected at each scan. Hens were euthanized at diagnosis of solid mass during scanning or at the end of the study; ovaries, fimbria and serum samples were collected. Normal hens (n = 10), hens with early (n = 7) and late-stage (n = 8) tumors were selected. Talin-1 expression in tissues and serum was determined by immunohistochemistry (IHC), Western blotting (WB), gene expression (qPCR), and immunoassay (ELISA). Significant differences in Talin-1 expression among all groups were determined by ANOVA and/or paired/unpaired t-tests, significance was taken when P< 0.05. Results: Expression of Talin-1was detected in all tissues with various intensities. Compared with normal, ovarian HGSC tissues showed intense expression of Talin-1 in IHC, WB and qPCRs ( P< 0.05). Similar patterns were observed in serum levels in ELISA ( P< 0.01) in the exploratory study. Prospective study in hens showed significant increase in serum Talin-1 levels even before the formation of a solid tumor mass in the ovary or fimbria detectable by TVUS. Conclusions: Elevated Talin-1 expression in early-stage ovarian HGSC tumors suggests its association with malignant development. Serum prevalence of Talin-1 during malignant transformation makes it a potential marker for early detection of HGSC and its progression. These results will serve as foundation for a clinical study with larger cohorts. Support: NIH R01 CA210370 (AB)