The increased expression of <scp>TCF</scp>3 is correlated with poor prognosis in Chinese patients with nasopharyngeal carcinoma

Shen, Xiaohe; Yuan, Jianmin; Zhang, Mengjie; Li, Wenhua; Ni, Bing; Wu, Yuzhang; Jiang, Li; Fan, Weiping; Tian, Zhiqiang

doi:10.1111/coa.12834

Cited by 10 publications

(6 citation statements)

References 26 publications

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“…TCF1 (TCF7) has also been shown to be overexpressed in renal cell carcinoma 19. Interestingly, Shen et al demonstrated that another member of LEF/TCF family, TCF3, had a higher expression in NPC than in non-tumorous nasopharyngeal tissues, and they also confirmed that increased expression of TCF3 was closely related to clinical stage, locoregional recurrence and distant metastasis of NPC, and thus resulted in shorter survival time and poorer prognosis 21. In our study, we observed that expression of TCF1 (TCF7) was higher in NPC than non-cancerous nasopharyngeal mucosa.…”

Section: Discussionmentioning

confidence: 98%

Expression of LEF1 and TCF1 (TCF7) proteins associates with clinical progression of nasopharyngeal carcinoma

Zhan

Feng

et al. 2019

J Clin Pathol

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AimsOur previous study has demonstrated that β-catenin pathway was abnormally activated in nasopharyngeal carcinoma (NPC). The purposes of the present study are to investigate whether the alterations of LEF1 and TCF1 (TCF7) proteins, the important components of the canonical Wnt/β-catenin pathway, are associated with clinicopathological features and prognostic implications.MethodsWe collected 391 cases of NPC, 53 non-cancerous control nasopharyngeal mucosa and 28 pairs of NPC and their matched metastases, detected expression of LEF1 and TCF1 (TCF7) proteins in these tissues by immunohistochemistry. ResultsResults showed that there were significantly increased expression of both LEF1 and TCF1 (TCF7) proteins and coexpression of LEF1 and TCF1 (TCF7) in NPC than these in non-cancerous nasopharyngeal mucosa (all p<0.001), as well as LEF1 and coexpression of LEF1 and TCF1 (TCF7) in matched metastasis NPCs than these in the primary NPCs (p=0.003 and p=0.014, respectively). In addition, expression of LEF1 and the coexpression of LEF1 and TCF1 (TCF7) proteins were positively correlated with lymph node metastasis (p=0.001 and p=0.020, respectively), advanced clinical stage (p<0.003 and p=0.027, respectively) and poor survival status of patients with NPC (p<0.001 and p=0.004, respectively). Moreover, multivariate Cox regression analysis identified that the positive expression of LEF1 was the independent poor prognostic factor for overall survival of patients with NPC (p<0.001).ConclusionsThe expression of LEF1 associated positively with TCF1 (TCF7) and clinical progression of NPC, and positive expression of LEF1 protein may act as valuable independent biomarker to predict poor prognosis for patients with NPC.

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Section: Discussionmentioning

confidence: 98%

Expression of LEF1 and TCF1 (TCF7) proteins associates with clinical progression of nasopharyngeal carcinoma

Zhan

Feng

et al. 2019

J Clin Pathol

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“…In addition, it has been shown to have oncogenic activities in vitro in a variety of malignancies including prostate, 23,24 esophageal 25 and breast cancer, 26 glioblastoma, 27 and chronic lymphocytic leukemia 28 . Increased expression of TCF3 is associated with adverse outcome in a number of cancers 29–32 . Examination of Oncomine databases revealed increased expression of TCF3 in prostate cancer compared to benign prostate ( p < .01) in 9 of 16 databases (including all of the databases with increased MEX3D; examples in Figure 4C).…”

Section: Resultsmentioning

confidence: 99%

MEX3D is an oncogenic driver in prostate cancer

et al. 2021

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Background Prostate cancer (PCa) is the most common visceral malignancy and the second leading cause of cancer deaths in US men. The two most common genetic alterations in PCa are expression of the TMPRSS2/ERG (TE) fusion gene and loss of the PTEN tumor suppressor. These genetic alterations act cooperatively to transform prostatic epithelium but the exact mechanisms involved are unclear. Methods Microarray expression analysis of immortalized prostate epithelial cells transformed by loss of PTEN and expression of the TE fusion revealed MEX3D as one of the most highly upregulated genes. MEX3D expression in prostate cancer was examined in patient samples and in silico. In vitro and in vivo studies to characterize the biological impact of MEX3D were carried out. Analysis of the TCGA PanCancer database revealed TCF3 as a major target of MEX3D. The induction of TCF3 by MEX3D was confirmed and the biological impact of TCF3 examined by in vitro studies. Results MEX3D is expressed at increased levels in prostate cancer and is increased by decreased PTEN and/or expression of the TE fusion gene and drives soft agar colony formation, invasion and tumor formation in vivo. The known oncogenic transcription factor TCF3 is highly correlated with MEX3D in prostate cancer. MEX3D expression strongly induces TCF3, which promotes soft agar colony formation and invasion in vitro. Conclusions Loss of PTEN and expression of the TE fusion gene in prostate cancer strongly upregulates expression of MEX3D and its target TCF3 and promotes transformation associated phenotypes via this pathway.

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“…Aberrant activation of TCF3 (E2A), most commonly, was correlated with the risk and onset of lymphoblastic leukemia [ 37 ]. Associations between TCF3 and other human malignancies, such nasopharyngeal carcinoma [ 13 ], breast cancer [ 38 ], colorectal cancer [ 39 ], blastemal Wilms tumors [ 40 ], have been identified as well. In this study, the integrated bioinformatic analyses via Oncomine, GSE datasets, and TCGA-CESC database indicated that TCF3 was upregulated in multiple cancers, including CC, and its high expression was predicted to be correlated with poor outcome of patients.…”

Section: Discussionmentioning

confidence: 99%

“…TCF3 protein exerts its cell type- or tissue-specific functions by forming a homodimer or a heterodimer with other bHLH proteins [ 9 ]. TCF3 was at first suggested to exert crucial functions during lymphocyte development [ 10 ], and studies have reported its involvement in the pathogenesis of several human malignancies, such as prostate cancer [ 11 ], breast cancer [ 12 ] and nasopharyngeal carcinoma [ 13 ]. Elevated expression of TCF3 has been associated with poor prognosis in CC [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

Transcriptional factor 3 binds to sirtuin 1 to activate the Wnt/β-catenin signaling in cervical cancer

Bai

et al. 2022

Bioengineered

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Transcriptional factor 3 (TCF3, also termed E2A), first reported to exert crucial functions during lymphocyte development, has been revealed to participate in the pathogenesis of human cancers. The aim of this work was to investigate the function of TCF3 in cervical cancer (CC) and the molecular interactions. The bioinformatics prediction suggested that TCF3 was highly expressed in CC and linked to poor prognosis. Increased TCF3 expression was identified in CC cell lines, and its downregulation reduced proliferation and migration of CC cells in vitro as well as growth of xenograft tumors in vivo . Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses showed that the TCF-3-related genes and genes showed differential expression between CC and normal tissues were mainly enriched in the Wnt/β-catenin pathway. TCF3 bound to sirtuin 1 (SIRT1) promoter for transcriptional activation, and SIRT1 promoted deacetylation and nuclear translocation of β-catenin in CC. SIRT1 overexpression blocked the role of TCF3 silencing and restored cell proliferation in vitro and tumor growth in vivo . Treatment with XAV-939, a β-catenin inhibitor, significantly suppressed the cell proliferation and tumor growth induced by SIRT1 overexpression. In conclusion, this study demonstrates that TCF3 augments progression of CC by activating SIRT1-mediated β-catenin signaling.

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The increased expression of TCF3 is correlated with poor prognosis in Chinese patients with nasopharyngeal carcinoma

Abstract: Our observations suggest, for the first time, that TCF3 is significantly associated with the development and progression of NPC, which can be used as an important prognostic marker for patients with NPC and may be an effective target for the treatment of NPC.

Cited by 10 publications

References 26 publications

Expression of LEF1 and TCF1 (TCF7) proteins associates with clinical progression of nasopharyngeal carcinoma

Expression of LEF1 and TCF1 (TCF7) proteins associates with clinical progression of nasopharyngeal carcinoma

MEX3D is an oncogenic driver in prostate cancer

Transcriptional factor 3 binds to sirtuin 1 to activate the Wnt/β-catenin signaling in cervical cancer

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