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

Dötzer, Katharina; Schlüter, Friederike; Koch, Franz Edler von; Brambs, Christine; Anthuber, S.; Frangini, Sergio; Czogalla, Bastian; Burges, Alexander; Werner, Jens; Mahner, Sven; Mayer, Barbara

doi:10.3390/biomedicines9030289

Cited by 11 publications

(8 citation statements)

References 55 publications

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“…There are a plethora of studies investigating different integrins in OC. Contrary to our findings, Dötzer et al [ 19 ] observed a high expression of integrin α2β1 in OC patients, which was identified as a marker for a poor prognosis with similar strength compared to FIGO stage and macroscopic residual tumor after surgery. High α2β1 expression in primary tumor was associated with a significant shorter PFS ( p = 0.035) and platinum-free interval ( p = 0.034).…”

Section: Discussioncontrasting

confidence: 99%

Role of integrins in the metastatic spread of high-grade serous ovarian cancer

Krajnak

Jäkel

Anić

et al. 2021

Arch Gynecol Obstet

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Purpose Integrins may be involved in the metastatic spread of high-grade serous ovarian cancer (HGSOC) which determines the therapeutical approach and prognosis. We investigated the integrin expression in primary tumor and metastases of advanced HGSOC. Methods The expression of integrin α2, α4, α5, α6, and β1 was assessed by immunostaining in tumor samples of the ovary, omentum, and peritoneum of each patient. Differences in integrin expression among tumor localizations and their association with clinicopathological parameters were examined by Fisher’s exact test. The impact of integrin expression on progression-free survival (PFS) and overall survival (OS) was examined by Cox regression and Kaplan–Meier analyses. Results Hundred and thirteen tumor samples of 40 HGSOC patients were examined. The expression of the integrins did not differ between the three tumor localizations (all p values > 0.05) with the exception of high expression of integrin α4 in primary tumor and omentum (52.5% versus 47.5%, p = 0.008) and primary tumor and peritoneum (52.5% versus 47.5%, p = 0.050). High expression of integrin α4 in peritoneum was associated with poorer PFS (HR 2.02 95% CI 1.01–4.05, p = 0.047), younger age (p = 0.047), and death (p = 0.046). Median PFS in patients with high expression of integrin α4 was 13.00 months, whereas median PFS in patients without high expression of integrin α4 was 21.00 months (p = 0.040). Expression of other integrins did not correlate with PFS or OS. Conclusion Expression of integrin α4 may be altered during the metastatic spread of HGSOC and affect prognosis, whereas expression of integrin α2, α5, α6, and β1 did not reveal any prognostic value.

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Section: Discussioncontrasting

confidence: 99%

Role of integrins in the metastatic spread of high-grade serous ovarian cancer

Krajnak

Jäkel

Anić

et al. 2021

Arch Gynecol Obstet

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“…Increased expression of integrin αV in PDAC cells has been associated with decreased patient survival ( 149 ). High expression of integrin α2β1 co-expressing HGFR or CD44v6 indicated worse progression-free survival in primary ovarian cancer and supported the hypothesis of mediating platinum resistance mediated by integrin α2β1 ( 171 ). Oxysterol-binding protein-like (OSBPL) family members potentially bound to integrins are highly upregulated in PDAC with poor outcomes in pancreatic ductal adenocarcinoma PDAC ( 172 ).…”

Section: Integrin and Endocrine-related Cancersmentioning

confidence: 53%

Mechanisms of Cell Adhesion Molecules in Endocrine-Related Cancers: A Concise Outlook

et al. 2022

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Chemotherapy is a critical treatment for endocrine-related cancers; however, chemoresistance and disease recurrence remain a challenge. The interplay between cancer cells and the tumor microenvironment via cell adhesion molecules (CAMs) promotes drug resistance, known as cell adhesion-mediated drug resistance (CAM-DR). CAMs are cell surface molecules that facilitate cell-to-cell or cell-to-extracellular matrix binding. CAMs exert an adhesion effect and trigger intracellular signaling that regulates cancer cell stemness maintenance, survival, proliferation, metastasis, epithelial–mesenchymal transition, and drug resistance. To understand these mechanisms, this review focuses on the role of CD44, cadherins, selectins, and integrins in CAM-DR in endocrine-related cancers.

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“…Our analysis demonstrated that patients with a combined high expression of HGFR and HER2/neu, EGFR, IGF1R, Mucin-1 and Integrin α2β1 show a very aggressive tumor biology with an impaired median survival compared to HGFR high-expressing tumors alone. These data show that the progression of primary ovarian cancer is a complex multifactorial process involving molecular crosstalks between different signaling pathways [ 22 ]. Multi-target biomarker-driven treatment may be a strategy to overcome platinum resistance and poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…Serial cryosections (5 µm) were performed. The samples were stained immunohistochemically with the avidin–biotin–peroxidase method as described in detail in [ 21 , 22 , 23 ]. Briefly, after fixation and blocking of unspecific Fc receptors and endogenous biotin, tissue sections were stained with the primary antibodies for one hour.…”

Section: Methodsmentioning

confidence: 99%

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Combined Expression of HGFR with Her2/neu, EGFR, IGF1R, Mucin-1 and Integrin α2β1 Is Associated with Aggressive Epithelial Ovarian Cancer

et al. 2022

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Hepatocyte growth factor receptor (HGFR), also known as c-mesenchymal–epithelial transition factor (c-MET), plays a crucial role in the carcinogenesis of epithelial ovarian cancer (EOC). In contrast, the mechanisms contributing to aberrant expression of HGFR in EOC are not fully understood. In the present study, the expression of HGFR with its prognostic and predictive role was evaluated immunohistochemically in a cohort of 42 primary ovarian cancer patients. Furthermore, we analyzed the dual expression of HGFR and other druggable biomarkers. In the multivariate Cox regression analysis, high HGFR expression was identified as an independent prognostic factor for a shorter progression-free survival (PFS) (hazard ratio (HR) 2.99, 95% confidence interval (CI95%) 1.01–8.91, p = 0.049) and overall survival (OS) (HR 5.77, CI95% 1.56–21.34, p = 0.009). In addition, the combined expression of HGFR, human epidermal growth factor receptor 2 (Her2/neu), epithelial growth factor receptor (EGFR), insulin-like growth factor 1 (IGF1R), Mucin-1 and Integrin α2β1 further significantly impaired PFS, platinum-free interval (PFI) and OS. Protein co-expression analyses were confirmed by transcriptomic data in a large, independent cohort of patients. In conclusion, new biomarker-directed treatment targets were identified to fight poor prognosis of primary EOC.

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

Cited by 11 publications

References 55 publications

Role of integrins in the metastatic spread of high-grade serous ovarian cancer

Role of integrins in the metastatic spread of high-grade serous ovarian cancer

Mechanisms of Cell Adhesion Molecules in Endocrine-Related Cancers: A Concise Outlook

Combined Expression of HGFR with Her2/neu, EGFR, IGF1R, Mucin-1 and Integrin α2β1 Is Associated with Aggressive Epithelial Ovarian Cancer

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