Twist expression in patients with cervical cancer is associated with poor disease outcome

Gong

Molecular Medicine Reports

et al. 2014

Abstract. The present study aimed to investigate the expression of interleukin-6 (IL-6) in gallbladder cancer (GBC) tissues and its correlation with survival rate. The association between IL-6 and epithelial-mesenchymal transition (EMT)-associated markers was also examined. Using immunohistochemistry, reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, the protein and mRNA expression levels of IL-6, Twist, E-cadherin and Vimentin in 20 GBC tissues were analyzed. The IL-6, Twist and Vimentin proteins were overexpressed in 40, 20 and 70% of the human GBC samples, respectively. The protein expression of E-cadherin was higher in only 5% of the GBC samples. These differences were significant (P<0.05). Western blot analysis also revealed overexpression of IL-6, Twist and Vimentin and underexpression of E-cadherin in the GBC samples with poor differentiation, local invasion and a higher tumor-node-metastasis (TNM) stage (P<0.05). Higher mRNA expression levels of IL-6, Twist and Vimentin and a reduced expression level of E-cadherin were also demonstrated in the GBC tissues (P<0.05). The degree of differentiation, local invasion, lymph node metastasis and clinical stage were significantly associated with the mRNA expression levels of IL-6, Twist and E-cadherin. The increased expression levels of IL-6 and Twist and the reduced expression of E-cadherin correlated with shorter median survival rates (P<0.05). Line regression results revealed correlation among the mRNA expression levels of IL-6, Twist, E-cadherin and Vimentin. To the best of our knowledge, the present study is the first to demonstrate that IL-6 is associated with EMT-associated markers, tumor differentiation, local invasion, TNM stage and survival rates in GBC.

Section: Discussionmentioning

confidence: 99%

Expression of interleukin-6 is associated with epithelial-mesenchymal transition and survival rates in gallbladder cancer

Gong

Molecular Medicine Reports

et al. 2014

Molecular and Clinical Oncology

“…The immunoresponse was also identified as an important prognostic factor for survival in cervical cancer (2). B7 family members and their receptors are crucial in the regulation of antigen-specific immune responses (3).…”

Section: Introductionmentioning

confidence: 99%

B7-H4 overexpression correlates with a poor prognosis for cervical cancer patients

Liu

Shibata

Koya³

et al. 2013

Abstract. Cervical cancer is a major global public health care concern and the second most commonly diagnosed malignancy among females worldwide. B7-H4 is an immunoregulatory protein that has been shown to be overexpressed in several types of cancer and is often associated with more advanced disease and poor prognosis. We investigated whether B7-H4 is a prognostic maker for cervical cancer by detecting its expression in cervical cancer specimens. Formalin-fixed, paraffin-embedded tissue blocks from cervical cancer were evaluated for B7-H4 expression by immunohistochemistry with free R software analysis. The intensity of B7-H4 immunoexpression was evaluated according to age, histological type, International Federation of Gynecology and Obstetrics (FIGO) stage, lymphovascular space invasion (LVSI) and lymph node status. We investigated the distribution and expression of B7-H4 in 102 cervical cancer specimens and determined the association between its expression and clinicopathological characteristics, including patient outcomes. Of the 102 specimens, 31 were found to be negative for B7-H4 immunoexpression, whereas 71 were B7-H4-positive. When classified by negative vs. positive expression, B7-H4 was not found to be associated with any of the clinicopathological parameters investigated. A positive B7-H4 expression significantly predicted poor overall survival (OS) when compared to negative expression (P<0.05). In the multivariate analysis, positive B7-H4 expression was identified as an independent prognostic factor for OS (P<0.05). Our data suggested that positive B7-H4 expression may be a useful biomarker in patients with cervical cancer likely to have an unfavorable clinical outcome.

“…Elevated Twist-1 expression is correlated with a poor prognosis and high risk of metastasis in breast, prostate, ovarian, cervical and many others human cancers (Elias et al, 2005;Kwok et al, 2005;Mironchik et al, 2005;Kyo et al, 2006;Puisieux et al, 2006;Hosono et al, 2007;Shibata et al, 2008). Recent reports suggest that high levels of Twist-1 confer cancer cells resistance to various chemotherapeutic drugs (Pham et al, 2007;Zhang et al, 2007;Shiota et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

PKB/AKT phosphorylation of the transcription factor Twist-1 at Ser42 inhibits p53 activity in response to DNA damage

et al. 2010

Protein kinase B (PKB/Akt) is ubiquitously expressed in cells. Phosphorylation of its multiple targets in response to various stimuli, including growth factors or cytokines, promotes cell survival and inhibits apoptosis. PKB is upregulated in many different cancers and a significant amount of the enzyme is present in its activated form. Here we show that PKB phosphorylates one of the anti-apoptotic proteins-transcription factor Twist-1 at Ser42. Cells expressing Twist-1 displayed inefficient p53 upregulation in response to DNA damage induced by c-irradiation or the genotoxic drug adriamycin. This influenced the activation of p53 target genes such as p21 Waf1 and Bax and led to aberrant cell-cycle regulation and the inhibition of apoptosis. The impaired induction of these p53 effector molecules is likely to be mediated by PKB-dependent phosphorylation of Twist-1 because, unlike the wild-type mutant, the Twist-1 S42A mutant did not confer cell resistance to DNA damage. Moreover, phosphorylation of Twist-1 at Ser42 was shown in vivo in various human cancer tissues, suggesting that this posttranslational modification ensures functional activation of Twist-1 after promotion of survival during carcinogenesis.