Epithelial-To-Mesenchymal Transition and Its Correlation With Clinicopathologic Features in Patients With Urothelial Carcinoma of the Bladder

Singh, Rinni; Ansari, Jamal Ahmad; Maurya, Niharika; Mandhani, Anil; Agrawal, Vinita; Garg, Minal

doi:10.1016/j.clgc.2016.07.021

Cited by 26 publications

(29 citation statements)

References 20 publications

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“…N-Cadherin and vimentin immunoexpressions are reported in urothelial tumor cells with stellate and fibroblast [9,[21][22][23]. Consistent with our previous report, novel/ focal expression of N-cadherin in epithelial/urothelial area has been observed to be significantly associated with tumor grade (p = 0.001) after combining all the stages together [9].…”

Section: Discussionsupporting

confidence: 88%

“…Zinc finger transcription factors, Snail and Slug, repress Ecadherin by binding to its promoter, upregulate mesenchymal proteins, and thereby promote EMT [7]. Experimental studies examine the pathological expression of putative markers of EMT and its association with increased motility and tumor invasion potential during development of UCB [8,9].…”

Section: Introductionmentioning

confidence: 99%

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Immunohistochemical Studies to Examine the Diagnostic and Prognostic Implications of Epithelial-to-Mesenchymal Transition in Patients with Urothelial Carcinoma of the Bladder

Singh

Mandhani²,

Agrawal

et al. 2019

SN Compr. Clin. Med.

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In the present study, quantitative expression of epithelial-to-mesenchymal transition (EMT)-associated markers was investigated immunohistochemically and their diagnostic and prognostic significance was evaluated in patients diagnosed with non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Immunohistochemical (IHC) staining was performed in a cohort of 65 formalin-fixed and paraffin-embedded human urinary bladder tumor tissues. Tissues' sections were obtained from archives of the Department of Pathology at SGPGIMS, India. Epithelial marker (Ecadherin), mesenchymal markers (N-cadherin and vimentin), and EMT-activating transcription factors (ATFs) (Snail and Slug) were examined for their cellular localization (membranous/cytoplasmic/nuclear) and quantitative expressions in terms of IHC score. Expression of the aforesaid markers was statistically correlated with various clinicohistopathological variables. These variables were obtained from histopathology reports and subsequent follow-up and OPD visits of patients. Impact of these markers was assessed on recurrence-free survival (RFS) in NMIBC cases and progression-free survival (PFS) in MIBC cases. The data was analyzed using SPSS 20.0 software. Focal loss of membranous E-cadherin showed statistical relevance with hematuria and tumor grade (p < 0.001, p = 0.005: independent sample t test) in MIBC patients. Novel membranous expression of N-cadherin exhibited relevance with hematuria (p = 0.011, one sample t test) in NMIBC, while membranous expression of vimentin showed correlation with tumor grade and age (p < 0.001, p < 0.001, one sample t test) in MIBC cases. Nuclear immunopositivity of Snail showed statistical association with tumor grade in both NMIBC and MIBC cases (p < 0.001, Moses non-parametric test; p < 0.001, one sample t test) and with hematuria in MIBC cases (p = 0.007, independent sample t test). Additionally, nuclear immunopositivity of Slug showed statistical association with tumor type in NMIBC and tumor grade in MIBC cases (p < 0.001, Moses non-parametric test; p < 0.001, one sample t test). Kaplan-Meier along with logrank statistics examined association between EMT profile and RFS in NMIBC cases (p < 0.001). Significant association of EMT biomarkers with clinicohistopathological outcomes may aid urologists to correlate its dynamic functions in urothelial tumorigenesis.

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Section: Discussionsupporting

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Immunohistochemical Studies to Examine the Diagnostic and Prognostic Implications of Epithelial-to-Mesenchymal Transition in Patients with Urothelial Carcinoma of the Bladder

Singh

Mandhani²,

Agrawal

et al. 2019

SN Compr. Clin. Med.

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“…32,33 In this study, we conducted GSVA to screen the most important Recent studies have revealed the involvement of EMT in the pathogenesis of cancers, including BLCA. 34 Some attribute the distinguishing characteristics between NMIBC and MIBC to differences in EMT-related programming. 35,36 EMT is a biological process that is triggered by many related genes, such as the epithelial marker E-cadherin, the mesenchymal markers vimentin and N-cadherin, and the group of transcriptional repressors Zeb, Snail, Slug and Twist.…”

Section: Discussionmentioning

confidence: 99%

An EMT‐related gene signature for the prognosis of human bladder cancer

Cao

Yuan

et al. 2019

J Cellular Molecular Medi

141

120

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The transition from non–muscle‐invasive bladder cancer (NMIBC) to muscle‐invasive bladder cancer (MIBC) is detrimental to bladder cancer (BLCA) patients. Here, we aimed to study the underlying mechanism of the subtype transition. Gene set variation analysis (GSVA) revealed the epithelial‐mesenchymal transition (EMT) signalling pathway with the most positive correlation in this transition. Then, we built a LASSO Cox regression model of an EMT‐related gene signature in BLCA. The patients with high risk scores had significantly worse overall survival (OS) and disease‐free survival (DFS) than those with low risk scores. The EMT‐related gene signature also performed favourably in the accuracy of prognosis and in the subtype survival analysis. Univariate and multivariate Cox regression analyses demonstrated that the EMT‐related gene signature, pathological N stage and age were independent prognostic factors for predicting survival in BLCA patients. Furthermore, the predictive nomogram model was able to effectively predict the outcome of BLCA patients by appropriately stratifying the risk score. In conclusion, we developed a novel EMT‐related gene signature that has tumour‐promoting effects, acts as a negative independent prognostic factor and might facilitate personalized counselling and treatment in BLCA.

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“…Due to its invasive nature, muscle-invasive bladder cancer (MIBC) has a high rate of mortality with a poor quality of life and an overall 5-year survival rate of 35-60% (2). The burden of cancer in non-MIBC (NMIBC) patients is primarily caused by subsequent adjuvant therapy, including intravesical chemotherapy; and the progression risk and high recurrence rate ranged from 50-90% with a 5-year survival rate of 70-80% worldwide in 2018 (3). Owing to the high recurrence and heterogeneity of this disease, the characterization of the molecular profile of tumors and investigating putative biomarkers is imperative.…”

Section: Introductionmentioning

confidence: 99%

circLPAR1 is a novel biomarker of prognosis for muscle‑invasive bladder cancer with invasion and metastasis by miR‑762

et al. 2019

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Circular RNAs (circRNAs) are a specific form of non-coding RNAs, that serve a pivotal role in the development of human diseases, including Alzheimer's disease and cancer; however, only a few are known with respect to cancer. The present study identified a novel circRNA, circ lysophosphatidic acid receptor 1 (LPAR1) (hsa_circ_0087960), derived from two exons 226 base pairs in length, in muscle-invasive bladder cancer (MIBC) tissues. circLPAR1 was identified to be lowly expressed in MIBC tissues in a cohort of 125 cases, and predicted a poor disease-specific survival time, compared with patients with high circLPAR1 expression (52.4 vs. 56.0 months; P=0.001) by univariate and multivariate Cox regression analyses. Matrigel and wound healing assays also demonstrated that the invasion of 5637 and T24 bladder cancer cells were significantly enhanced following the knockdown of circLPAR1 by small interfering RNA (si-circLPAR1-1 in T24 cell line, P= 0.01; si-circLPAR1-2 in 5637 cell line, P= 0.003; si-circLPAR1-2 in T24 cell line, P= 0.002; si-circLPAR1-2 in 5637 cell line, P= 0.006). The bioinformatics analysis indicated that circLPAR1 may harbor specific microRNAs (miRNAs) according to the miRNAs seed sequence matching. A luciferase reporter assay revealed that miR-762 can inhibit the activity of the transfected luciferase gene when inserted in a circLPAR1 wild-type fragment, and this inhibition could be alleviated when the luciferase gene was inserted in a circLPAR1 fragment with the mutated miR-762 target site. In conclusion, the circLPAR1 may function as a potential novel and stable biomarker for the prognosis of MIBC and may be associated with the invasion and metastasis by miR-762.

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Epithelial-To-Mesenchymal Transition and Its Correlation With Clinicopathologic Features in Patients With Urothelial Carcinoma of the Bladder

Cited by 26 publications

References 20 publications

Immunohistochemical Studies to Examine the Diagnostic and Prognostic Implications of Epithelial-to-Mesenchymal Transition in Patients with Urothelial Carcinoma of the Bladder

Immunohistochemical Studies to Examine the Diagnostic and Prognostic Implications of Epithelial-to-Mesenchymal Transition in Patients with Urothelial Carcinoma of the Bladder

An EMT‐related gene signature for the prognosis of human bladder cancer

circLPAR1 is a novel biomarker of prognosis for muscle‑invasive bladder cancer with invasion and metastasis by miR‑762

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