Cytoplasmic expression of Twist1, an EMT-related transcription factor, is associated with higher grades renal cell carcinomas and worse progression-free survival in clear cell renal cell carcinoma

Rasti, A. and Madjd, Z. and Abolhasani, M. and Mehrazma, M. and Janani, L. and Saeednejad Zanjani, L. and Asgari, M. (2018) Cytoplasmic expression of Twist1, an EMT-related transcription factor, is associated with higher grades renal cell carcinomas and worse progression-free survival in clear cell renal cell carcinoma. Clinical and Experimental Medicine, 18 (2). pp. 177-190.

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Abstract

Twist1 is a key transcription factor, which confers tumor cells with cancer stem cell (CSC)-like characteristics and enhances epithelial�mesenchymal transition in pathological conditions including tumor malignancy and metastasis. This study aimed to evaluate the expression patterns and clinical significance of Twist1 in renal cell carcinoma (RCC). The cytoplasmic and nuclear expression of Twist1 were examined in 252 well-defined renal tumor tissues, including 173 (68.7) clear cell renal cell carcinomas (ccRCC), 45 (17.9) papillary renal cell carcinomas (pRCC) and 34 (13.5) chromophobe renal cell carcinoma, by immunohistochemistry on a tissue microarray. The association between expression of this marker and clinicopathologic parameters and survival outcomes were then analyzed. Twist1 was mainly localized to the cytoplasm of tumor cells (98.8). Increased cytoplasmic expression of Twist1 was associated with higher grade tumors (P = 0.045), renal vein invasion (P = 0.031) and microvascular invasion (P = 0.044) in RCC. It was positively correlated with higher grade tumors (P = 0.026), shorter progression-free survival time (P = 0.027) in patients with ccRCC, and also with higher stage in pRCC patients (P = 0.036). Significantly higher cytoplasmic expression levels of Twist1 were found in ccRCC and pRCC subtypes, due to their more aggressive tumor behavior. Increased cytoplasmic expression of Twist1 had a critical role in worse prognosis in ccRCC. These findings suggest that cytoplasmic, rather than nuclear expression of Twist1 can be considered as a prognostic and therapeutic marker for targeted therapy of RCC, especially for ccRCC patients. © 2017, Springer International Publishing AG, part of Springer Nature.

Item Type: Article
Additional Information: cited By 1
Uncontrolled Keywords: Twist related protein 1; nuclear protein; Twist related protein 1; TWIST1 protein, human, adult; Article; cancer grading; cancer patient; cancer prognosis; cancer survival; controlled study; cytoplasm; disease association; disease specific survival; female; human; human tissue; immunohistochemistry; kidney tissue; kidney vein; major clinical study; male; priority journal; progression free survival; protein expression; protein function; renal cell carcinoma; tissue microarray; tumor invasion; aged; cell nucleus; kidney tumor; metabolism; middle aged; pathology; procedures; prognosis; renal cell carcinoma; survival analysis; very elderly, Adult; Aged; Aged, 80 and over; Carcinoma, Renal Cell; Cell Nucleus; Cytoplasm; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Neoplasm Grading; Neoplasm Invasiveness; Nuclear Proteins; Prognosis; Survival Analysis; Tissue Array Analysis; Twist-Related Protein 1
Subjects: WJ Urogenital System
Depositing User: eprints admin
Date Deposited: 31 Dec 2018 09:40
Last Modified: 24 Aug 2019 05:46
URI: http://eprints.iums.ac.ir/id/eprint/6037

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