Prognostic Significance of Twist and N-Cadherin Expression in NSCLC

Hui, Lian; Zhang, Siyang; Dong, Xin-Jun; Tian, Dean; Cui, Zeshi; Qiu, Xueshan

doi:10.1371/journal.pone.0062171

Cited by 81 publications

(79 citation statements)

References 36 publications

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“…This finding was not consistent with those of other studies, which showed that Twist1 depletion reduced ATC cell viability [20]. Data have shown that Twist1 depletion induces lung cancer cell apoptosis [31]. This suggested that PTC proliferation may be regulated by other factors.…”

Section: Discussioncontrasting

confidence: 68%

Twist1 regulates the epithelial–mesenchymal transition via the NF-κB pathway in papillary thyroid carcinoma

Shan

Gao

et al. 2015

Endocrine

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Expression of the oncogene Twist1 is correlated with tumor development and metastasis. Recent studies have suggested that the epithelial-to-mesenchymal transition (EMT) is necessary for tumor progression and metastases. Little is known concerning the role of Twist1 and EMT in thyroid cancer. In the present work, the expression levels of Twist1 and one marker of EMT, vimentin, were measured in papillary thyroid carcinoma (PTC). The results showed Twist1 expression to be correlated only with cancer lymph node metastases (P = 0.004) and not with other clinicopathological indicators. Moreover, Twist1 expression was positively correlated with the expression of vimentin (r = 0.408, P = 0.003). In vitro studies further indicated that reducing Twist1 expression using short hairpin RNA against Twist1 can decrease the invasive and metastatic properties of PTC cells and that the down-regulation of Twist1 can reverse EMT by increasing the expression of E-cadherin and down-regulating the expression of vimentin in the PTC cell line IHH-4. To investigate the effects on Twist1, the PTC cell lines TPC-1 and BCPAP were treated with TNF-α, resulting in Twist1 up-regulation that was dependent on NF-κB activation. After the inhibition of NF-κB activity with Bay11-7082, the Twist1 mRNA and protein levels could not be increased. The decline in the Twist1 mRNA and protein levels rendered the cancer cells less invasive. Thus, we conclude that Twist1 plays an important role in the EMT of PTC via the NF-κB pathway.

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Section: Discussioncontrasting

confidence: 68%

Twist1 regulates the epithelial–mesenchymal transition via the NF-κB pathway in papillary thyroid carcinoma

Shan

Gao

et al. 2015

Endocrine

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“…Lymph node metastasis was evaluated in 21 studies with 3900 patients (positive lymph node metastasis versus negative lymph node metastasis) . Pooled RR indicated that increased N‐cadherin apt to cause lymph node metastasis (RR = 1.16, 95%CI [1.00, 1.35], I 2 = 57.6%, P = .806; Figure A).…”

Section: Resultsmentioning

confidence: 99%

Upregulated N‐cadherin expression is associated with poor prognosis in epithelial‐derived solid tumours: A meta‐analysis

Luo

Zhang

et al. 2018

Eur J Clin Investigation

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BackgroundN‐cadherin is an important molecular in epithelial‐mesenchymal transition (EMT) and has been reported to be associated with aggressive behaviours of tumours. However, prognostic value of N‐cadherin in solid malignancies remains controversially.Materials and MethodsThe Pubmed/MELINE and EMBASE databases were used for a comprehensive literature searching. Pooled risk ratio (RR) and hazard ratio (HR) with their corresponding 95% confidence intervals (CIs) were employed to quantify the prognostic role.ResultsInvolving 36 studies with 5705 patients were performed to investigate relationships between N‐cadherin upregulation and clinicopathological features, survival. Results suggested upregulated N‐cadherin was associated with lymph node metastasis (RR = 1.16, 95% CI [1.00, 1.35]), higher histological grade (RR = 1.36, 95%CI [1.14, 1.62]), angiolymphatic invasion (RR = 1.19, 95% CI [1.06, 1.34]) and advanced clinical stage (RR = 1.32, 95% CI [1.06, 1.64]), while upregulated N‐cadherin was apt to be associated with distant metastasis (RR = 1.43, 95% CI [0.99, 2.05]). Moreover, N‐cadherin was correlated with poor prognosis of 3‐year survival (HR = 1.78, 95% CI [1.51, 2.10]), 5‐year survival (HR = 1.57, 95% CI [1.17, 2.10]) and overall survival (OS) (HR = 1.32, 95% CI [1.20, 1.44]). Subgroup analyses according to cancer types were also conducted for applying these conclusions to some tumours more properly. No publication bias was found except subgroup analysis of distant metastasis (P = .652 for Begg's test and 0.023 for Egger's test).ConclusionsTaken together, upregulation of N‐cadherin is associated with more aggressive behaviours of epithelial‐derived solid malignancies and can be regarded as a predictor of poor survival.

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“…IHC expression of VIMENTIN was also previously investigated in NSCLC, with 7%‐66% of overexpression depending on the IHC cutoff value . One study quantified CDH2 expression by RT‐qPCR in 30 NSCLC (stages I to IV) and found that 67% of tumors had N‐Cadherin overexpression, with a bad prognosis value . Four studies have found an association between VIMENTIN IHC overexpression and N+ status of NSCLC .…”

Section: Discussionmentioning

confidence: 99%

SNAI2 and TWIST1 in lymph node progression in early stages of NSCLC patients

et al. 2018

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Lymph node metastasis is an important prognosis factor in non‐small cell lung cancer (NSCLC) patients. The aim of this study was to investigate the role of epithelial to mesenchymal transition (EMT) in lymph node progression in the early stages of NSCLC. We studied a retrospective cohort of 160 consecutive surgically treated NSCLC patients with available frozen tumor samples for expression of EMT markers (CDH1, CTNNB1, CDH2, and VIMENTIN), inducers (TGFB1, c‐MET, and CAIX), and transcription factors (EMT‐TF:SNAI1, SNAI2, ZEB1, TWIST1, and TWIST2). Partial EMT was more frequent in N1‐2 (N+) vs N0 patients (P < .01). TGFB1 (P = .02) as well as SNAI2 (P < .01) and TWIST1 (P = .04) were the most differentially expressed genes in N+ tumors. In this group, ZEB1 was correlated with all EMT inducers and other EMT‐TFs were overexpressed depending on the inducers. CAIX was an independent prognostic factor for overall survival (IC 95% HR: 1.10‐5.14, P = .03). Partial EMT is involved in lymph node progression of NSCLC patients and depends on the TGFβ pathway. EMT‐TFs are differentially expressed depending on EMT inducers. CAIX might be a relevant prognostic marker in early stage NSCLC.

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Prognostic Significance of Twist and N-Cadherin Expression in NSCLC

Cited by 81 publications

References 36 publications

Twist1 regulates the epithelial–mesenchymal transition via the NF-κB pathway in papillary thyroid carcinoma

Twist1 regulates the epithelial–mesenchymal transition via the NF-κB pathway in papillary thyroid carcinoma

Upregulated N‐cadherin expression is associated with poor prognosis in epithelial‐derived solid tumours: A meta‐analysis

SNAI2 and TWIST1 in lymph node progression in early stages of NSCLC patients

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