Integrin α2β1 Represents a Prognostic and Predictive Biomarker in Primary Ovarian Cancer

• Main Authors: Katharina Dötzer, Friederike Schlüter, Franz Edler von Koch, Christine E. Brambs, Sabine Anthuber, Sergio Frangini, Bastian Czogalla, Alexander Burges, Jens Werner, Sven Mahner, Barbara Mayer
• Format: Article
• Language: English
• Published: MDPI AG 2021-03-01
• Series: Biomedicines
• Subjects: primary ovarian cancer; integrin α2β1; prognostic factor; predictive factor; immune infiltrate; targeted therapy
• Online Access: https://www.mdpi.com/2227-9059/9/3/289

Currently, the same first-line chemotherapy is administered to almost all patients suffering from primary ovarian cancer. The high recurrence rate emphasizes the need for precise drug treatment in primary ovarian cancer. Being crucial in ovarian cancer progression and chemotherapeutic resistance, integrins became promising therapeutic targets. To evaluate its prognostic and predictive value, in the present study, the expression of integrin α2β1 was analyzed immunohistochemically and correlated with the survival data and other therapy-relevant biomarkers. The significant correlation of a high α2β1-expression with the estrogen receptor alpha (ERα; <i>p</i> = 0.035) and epithelial growth factor receptor (EGFR; <i>p</i> = 0.027) was observed. In addition, high α2β1-expression was significantly associated with a low number of tumor-infiltrating immune cells (CD3 intratumoral, <i>p</i> = 0.017; CD3 stromal, <i>p</i> = 0.035; PD-1 intratumoral, <i>p</i> = 0.002; PD-1 stromal, <i>p</i> = 0.049) and the lack of PD-L1 expression (<i>p</i> = 0.005). In Kaplan–Meier survival analysis, patients with a high expression of integrin α2β1 revealed a significant shorter progression-free survival (PFS, <i>p</i> = 0.035) and platinum-free interval (PFI, <i>p</i> = 0.034). In the multivariate Cox regression analysis, integrin α2β1 was confirmed as an independent prognostic factor for both PFS (<i>p</i> = 0.021) and PFI (<i>p</i> = 0.020). Dual expression of integrin α2β1 and the hepatocyte growth factor receptor (HGFR; PFS/PFI, <i>p</i> = 0.004) and CD44v6 (PFS, <i>p</i> = 0.000; PFI, <i>p</i> = 0.001; overall survival [OS], <i>p</i> = 0.025) impaired survival. Integrin α2β1 was established as a prognostic and predictive marker in primary ovarian cancer with the potential to stratify patients for chemotherapy and immunotherapy, and to design new targeted treatment strategies.