<i>CFL1</i> expression levels as a prognostic and drug resistance marker in nonsmall cell lung cancer

Castro, Mauro A. A.; Dal‐Pizzol, Felipe; Zdanov, Stéphanie; Soares, Márcio; Müller, Carolina; Lopes, Fernanda Machado; Zanotto-Filho, Alfeu; Fernandes, Marilda da Cruz; Moreira, José Cláudio Fonseca; Shacter, Emily; Klamt, Fábio

doi:10.1002/cncr.25125

Cited by 64 publications

(53 citation statements)

References 91 publications

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“…Therefore, CFL1 immunohistochemical expression is specific to PCa, and is associated with the aggressiveness of the phenotype. This is consistent with a number of studies that have reported CFL1 to be associated with a more aggressive phenotype and with tumor progression in various solid tumor tissues (12)(13)(14)(15). For instance, CFL1 has been reported to play a major role in tumor progression in ovarian carcinomas, as nearly 64% of all ovarian tumors are positive for CFL1 (16), upregulation of phosphorylated CFL1 levels result in increased chemoresistance (17) and the patients with CFL1-positive tumors demonstrate decreased progression-free survival rates compared with the patients with CFL1-negative lesions (18).…”

Section: Discussionsupporting

confidence: 93%

Overexpression of cofilin 1 in prostate cancer and the corresponding clinical implications

Lü

Luo

et al. 2015

Oncology Letters

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Abstract. Cofilin 1 (CFL1) is a cytoskeletal protein and overexpression of the protein has been associated with aggressiveness in certain types of malignancies. The aim of the present study was to investigate the clinical implications of CFL1 expression in prostate cancer (PCa). Immunohistochemical analysis was performed using formalin-fixed paraffin-embedded tissue sections obtained from 111 patients with PCa and 47 patients with benign prostatic hyperplasia (BPH). In total, 78 (70.3%) out of 111 PCa tissues were found to express the CFL1 protein, while no expression was detected in BPH tissues. In addition, CFL1 was also observed to be significantly associated with the Gleason score (GS; <7 vs. ≥7; P<0.0001) and presence of lymph node metastasis (presence vs. absence; P<0.0001). However, there was no association between the expression of CFL1 and other clinicopathological variables, such as age (<69 years vs. ≥69 years; P= 0.54), pre-operative prostate specific antigen level (<20 ng/ml vs. ≥20 ng/ml; P= 0.45) and pathological stage (T2 vs. ≥T3a; P= 0.055). In addition, 35 tissues (31.5%) were observed to possess a CFL1-positive mesenchyme. CFL1 expression was revealed to be an independent predictive factor for a high GS. The status of CFL1 expression in the mesenchyme also found to individually predict extraprostatic extension in PCa patients, based on multivariate analysis. The results of the present study indicated that CFL1 may specifically predict the development of PCa, and that the expression of CFL1 in the mesenchyme may be closely associated with the development of lymph node metastasis. IntroductionProstate cancer (PCa) is one of the most common non-cutaneous malignancies in males. Since the introduction of the prostate specific antigen (PSA)-based screening strategy in clinical practice, a marked increase in the incidence of PCa has been observed (1). Although the use of this screening strategy has resulted in a 40% reduction in PCa-associated mortality, the majority of patients succumb to the disease once metastasis has occurred. In addition, overtreatment of indolent PCa has emerged. This phenomenon may account for the deficiencies in accurate diagnosis and risk stratification. Therefore, the identification and validation of novel biomarkers for PCa should be considered a priority (2).Cofilin 1 (CFL1) is the non-muscle isoform of the product of the CFL1 gene (Gene ID, 1072). CFL1 is a small ubiquitous protein that is able to bind monomeric globular (G) and filamentous actin and inhibits the polymerization of monomeric G-actin in a pH-dependent manner (3), playing a key role in cell migration and cytokinesis (4). This protein is reported to be directly associated with the invasion, metastasis and chemoresistance of various human malignant solid tumors (5,6). However, no previous studies regarding CFL1 expression and its association with clinicopathological features in PCa are available in the literature. The expression of CFL1 and its clinical implications in PCa are investigated in the present stud...

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Section: Discussionsupporting

confidence: 93%

Overexpression of cofilin 1 in prostate cancer and the corresponding clinical implications

Lü

Luo

et al. 2015

Oncology Letters

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“…CFL1 and destrin are both actin-depolymerizing proteins and are involved in the organization of the cytoskeleton. A number of authors have reported CFL1 and destrin differential expression in cancer cells (13,(22)(23)(24)(25). To the best of our knowledge, we report for the first time their function related with drug resistance in ovarian cancer.…”

Section: Discussionmentioning

confidence: 66%

“…The spontaneous overexpression of CFL1 may be detected in invasive sub-populations of breast tumor cells in rats, as well as in biopsies of oral, renal, non-small cell lung cancer (NSCLC) and ovarian carcinoma. High CFL1 levels are correlated with lower overall survival rates and resistance to several alkylating drugs in NSCLC patients (13,(23)(24)(25). The overexpression of CFL was also detected in cisplatin-resistant cells (13).…”

Section: Discussionmentioning

confidence: 96%

Upregulation of phosphorylated cofilin 1 correlates with taxol resistance in human ovarian cancer in vitro and in vivo

Yin

Mao³

et al. 2012

Oncology Reports

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Abstract. The acquisition of chemoresistance is a major therapeutic obstacle in the clinical treatment of ovarian cancer. Diagnosing chemoresistance in ovarian cancer patients at an early stage is necessary for prognosis, but at present significant proteins related to chemoresistance that may indicate and reverse chemoresistance in human ovarian cancer have not been discovered. In this study, we demonstrated that the protein, phosphorylated cofilin 1 (p-CFL1) correlates with taxol resistance in human ovarian cancer cells. The total proteins of two sensitive (SKOV3 and A2780) and three taxolresistant (SKOV3/TR2500, SKOV3/TR30 and A2780/TR) human ovarian cancer cell lines were isolated by 2-dimensional gel electrophoresis (2-DE). Twenty-two protein spots in all samples were revealed to be significantly different in spot intensity by statistical analysis, 16 of which were identified using matrix-assisted laser desorption ionization-time-of-flightmass spectrometry (MALDI-TOF-MS). Cofilin 1 (CFL1) was selected as a candidate which may play an important role in taxol resistance. Higher expression levels of p-CFL1 in taxolresistant cells were demonstrated. Furthermore, the levels of p-CFL1 in primary human ovarian cancer tissues were shown to be significantly higher in chemoresistant cases compared to those in chemosensitive ones. These findings suggest that p-CFL1 is upregulated in taxol-resistant ovarian cancer and this upregulation is a chara cteristic of taxol resistance both in vitro and in vivo. However, the mechanisms need to be further elucidated.

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“…These results were corresponded * Results are shown as a range of the data obtained for identified proteins from different samples. to the data of Davila et al [40] who at comparative study of proteins of BPH-1 and PC-3 cells did not detect any changes in the level of Cofilin 1, though the increased expression of Cofilin 1 was observed in the cells of colorectal and lung cancer [21,30].…”

Section: Comparative Analysis Of Protein Fractionsmentioning

confidence: 72%

Comparative Proteomic Study of Proteins in Prostate Cancer and Benign Hyperplasia Cells

Шишкин¹,

Kovaleva²,

Ivanov³

2011

J Cancer Sci Ther

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Comparative proteomic studies of proteins in DU-145, PC-3, LNCaP and BPH-1 cultivated cells as well as in prostate tissue samples obtained from patients with benign and malignant tumors showed differences in protein profiles, in particular, high content in tissue samples of four isoforms of transgelin and profilin-1. Increased expression of protein Dj-1 was observed in cancer cells and biopsy samples of prostate cancer as opposed to BPH-1 cells and biopsy samples of tissues with benign hyperplasia. Dramatic reduction of serpin H1 was noted in the range of cell lines: BPH-1 → РС-3 → DU-145 → LNCaP. Thus, the obtained data are indicative of protein Dj-1 and serpin H1 participation in formation of the cancer phenotype in prostate cells.

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CFL1 expression levels as a prognostic and drug resistance marker in nonsmall cell lung cancer

Cited by 64 publications

References 91 publications

Overexpression of cofilin 1 in prostate cancer and the corresponding clinical implications

Overexpression of cofilin 1 in prostate cancer and the corresponding clinical implications

Upregulation of phosphorylated cofilin 1 correlates with taxol resistance in human ovarian cancer in vitro and in vivo

Comparative Proteomic Study of Proteins in Prostate Cancer and Benign Hyperplasia Cells

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