High Cytoplasmic and Membranous Versus Nuclear Talin-1 Expression Associated With Malignancy Potential and Determine Survival and Metastasis of Clear Cell Renal Cell Carcinoma

Abstract

Background: Talin-1 as a cytoskeleton protein participates in cell migration and has an essential role in cell adhesion, proliferation, tumorigenesis, invasion, and metastasis in various types of malignancies.Methods: Bioinformatics analysis has been performed by a using protein-protein interaction network, analyses among PRIDE databases, and indicated that Talin-1 protein as a potential prognostic focal adhesion factor in renal cell carcinoma (RCC). We, therefore, examined the protein expression levels and prognostic significance of Talin-1 with clinical follow-up in a total of 269 formalin-fixed paraffin-embedded tissue specimens from three important subtypes of RCC undergone radical nephrectomy and 30 adjacent normal tissues in three levels including, membrane, cytoplasm, and nucleus using immunohistochemistry on tissue microarrays. Then, we used a combined analysis with B7-H3 to confirm that Talin-1 may be related to metastasis.Results: The results showed that the expression of Talin-1 is significantly upregulated in most RCCs compared to adjacent normal tissues in protein levels. Further, there was a statistically significant difference between the membranous and cytoplasmic expression of Talin-1 and different subtypes of RCC (P < 0.001, P = 0.003, respectively). High membranous and cytoplasmic expression of Talin-1 was significantly associated with advanced nucleolar grade (P < 0.001, all), microvascular invasion (P = 0.007, P = 0.004), histological tumor necrosis (P = 0.020, P = 0.018), and invasion to Gerota’s fascia (P = 0.025, P = 0.050) in clear cell RCC (ccRCC). In addition, high membranous and cytoplasmic expression of Talin-1 was associated with significantly poorer disease-specific survival (DSS) (P = 0.043, P = 0.024, respectively) and progression-free survival (PFS) (P = 0.046, only in cytoplasmic expression). The co-expression of cytoplasmic Talin-1High /B7-H3High was observed to be associated with more aggressive tumor behavior and metastasis. Moreover, increased cytoplasmic expression of Talin-1High/B7-H3High compared to the other phenotypes was associated with poor prognosis and progression of the disease in patients with distant metastasis. Conclusion: Collectively, these observations indicate that Talin-1 is an important molecule involved in the spread and progression of ccRCC when expressed particularly in the cytoplasm and may serve as a novel prognostic biomarker in ccRCC if follow up time more prolonged.