Prognostic value of PAX9 in patients with esophageal squamous cell carcinoma and its prediction value to radiation sensitivity

Tan, Bingxu; Wang, Jianbo; Song, Qingxu; Wang, Nana; Jia, Yibin; Yao, Bin; Liu, Zhulong; Zhang, Xiaomei; Cheng, Yufeng

doi:10.3892/mmr.2017.6626

Cited by 18 publications

(13 citation statements)

References 52 publications

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“…It is involved in cell proliferation, apoptotic resistance, and cell migration and has been shown to be a prognostic marker of esophageal squamous cell carcinoma. 12 AXIN2 is a negative regulator of the catenin Wnt signaling pathway and is expressed in dental papilla mesenchyme. 5 Mutations in AXIN2 have been associated with tooth agenesis, with the phenotype presenting as a mix of anterior and posterior tooth agenesis.…”

Section: Odontogenesismentioning

confidence: 99%

Diagnosis of Tooth Agenesis in Childhood and Risk for Neoplasms in Adulthood

Ritwik

Patterson

2018

TOJ

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Background: Tooth agenesis, the congenital absence of one or more teeth, can be diagnosed in children in the first decade of life. Tooth agenesis is a phenotypic feature of conditions such as ectodermal dysplasia, cleft lip, cleft palate, Down syndrome, and Van der Woude syndrome. Tooth agenesis can also be nonsyndromic. Studies have shown an association between the genetic determinants of nonsyndromic tooth agenesis and neoplasms in adulthood. Methods: This review of the implications of tooth agenesis as a risk indicator for neoplasms in adulthood is based on a search of PubMed to identify published case series, case reports, and review articles. The reference articles were manually searched. The search was limited to articles published in the English language. Results: Neoplasms reported in patients with tooth agenesis include colorectal neoplasms and epithelial ovarian cancer, as well as family histories of breast cancer, prostate cancer, and cancers of the brain and nervous system. Conclusion: Although odontogenesis and tumorigenesis may seem to be unrelated processes, the clinical association between the two highlights the overlap of genetic determinants and molecular pathways. Tooth agenesis can be diagnosed during childhood and should be considered a marker for risk of neoplasms in adulthood. Healthcare providers should identify tooth agenesis and provide appropriate anticipatory guidance.Tooth agenesis can be classified based on the number of congenitally missing teeth. Hypodontia refers to the absence of fewer than 6 teeth (not including third molars). 5,6

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Section: Odontogenesismentioning

confidence: 99%

Diagnosis of Tooth Agenesis in Childhood and Risk for Neoplasms in Adulthood

Ritwik

Patterson

2018

TOJ

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“…In human ESCC tissue samples, PAX9 was found to be lost or downregulated, and progressive loss of PAX9 expression was correlated with increasing malignancy . PAX9 expression was associated with better survival and radiosensitivity . In human OSCC cells, PAX9 expression was essential for cell growth and survival .…”

Section: Introductionmentioning

confidence: 96%

PAX9 regulates squamous cell differentiation and carcinogenesis in the oro‐oesophageal epithelium

Xiong

Ren

Chen

et al. 2017

The Journal of Pathology

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PAX9 is a transcription factor of the PAX family characterized by a DNA-binding paired domain. Previous studies have suggested a potential role of PAX9 in squamous cell differentiation and carcinogenesis of the oro-oesophageal epithelium. However, its functional roles in differentiation and carcinogenesis remain unclear. In this study, Pax9 deficiency in mouse oesophagus promoted cell proliferation, delayed cell differentiation, and altered the global gene expression profile. Ethanol exposure downregulated PAX9 expression in human oesophageal epithelial cells in vitro and mouse forestomach and tongue in vivo. We further showed that PAX9 was downregulated in human oro-oesophageal squamous cell carcinoma (OESCC), and its downregulation was associated with alcohol drinking and promoter hypermethylation. Moreover, ad libitum feeding with a liquid diet containing ethanol for 40 weeks or Pax9 deficiency promoted N-nitrosomethylbenzylamine-induced squamous cell carcinogenesis in mouse tongue, oesophagus, and forestomach. In conclusion, PAX9 regulates squamous cell differentiation in the oro-oesophageal epithelium. Alcohol drinking and promoter hypermethylation are associated with PAX9 silencing in human OESCC. PAX9 downregulation may contribute to alcohol-associated oro-oesophageal squamous cell carcinogenesis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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“…To date, only one study has described the role of PAX9 as a predictive marker in cancer. Tan et al (2017) observed an interaction between the expression of this gene and postoperative radiotherapy in esophageal squamous cell carcinoma, wherein patients with high expression showed greater life expectancy and delayed disease reoccurrence, granting this gene a positive role as a marker of radiosensitivity in this type of malignancy [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer

et al. 2021

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Background In an effort to contribute to overcoming the platinum resistance exhibited by most solid tumors, we performed an array of epigenetic approaches, integrating next-generation methodologies and public clinical data to identify new potential epi-biomarkers in ovarian cancer, which is considered the most devastating of gynecological malignancies. Methods We cross-analyzed data from methylome assessments and restoration of gene expression through microarray expression in a panel of four paired cisplatin-sensitive/cisplatin-resistant ovarian cancer cell lines, along with publicly available clinical data from selected individuals representing the state of chemoresistance. We validated the methylation state and expression levels of candidate genes in each cellular phenotype through Sanger sequencing and reverse transcription polymerase chain reaction, respectively. We tested the biological role of selected targets using an ectopic expression plasmid assay in the sensitive/resistant tumor cell lines, assessing the cell viability in the transfected groups. Epigenetic features were also assessed in 189 primary samples obtained from ovarian tumors and controls. Results We identified PAX9 and FKBP1B as potential candidate genes, which exhibited epigenetic patterns of expression regulation in the experimental approach. Re-establishment of FKBP1B expression in the resistant OVCAR3 phenotype in which this gene is hypermethylated and inhibited allowed it to achieve a degree of platinum sensitivity similar to the sensitive phenotype. The evaluation of these genes at a translational level revealed that PAX9 hypermethylation leads to a poorer prognosis in terms of overall survival. We also set a precedent for establishing a common epigenetic signature in which the validation of a single candidate, MEST, proved the accuracy of our computational pipelines. Conclusions Epigenetic regulation of PAX9 and FKBP1B genes shows that methylation in non-promoter areas has the potential to control gene expression and thus biological consequences, such as the loss of platinum sensitivity. At the translational level, PAX9 behaves as a predictor of chemotherapy response to platinum in patients with ovarian cancer. This study revealed the importance of the transcript-specific study of each gene under potential epigenetic regulation, which would favor the identification of new markers capable of predicting each patient’s progression and therapeutic response.

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Prognostic value of PAX9 in patients with esophageal squamous cell carcinoma and its prediction value to radiation sensitivity

Cited by 18 publications

References 52 publications

Diagnosis of Tooth Agenesis in Childhood and Risk for Neoplasms in Adulthood

Diagnosis of Tooth Agenesis in Childhood and Risk for Neoplasms in Adulthood

PAX9 regulates squamous cell differentiation and carcinogenesis in the oro‐oesophageal epithelium

Transcriptional epigenetic regulation of Fkbp1/Pax9 genes is associated with impaired sensitivity to platinum treatment in ovarian cancer

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