PITX3 DNA methylation is an independent predictor of overall survival in patients with head and neck squamous cell carcinoma

Sailer, Verena; Holmes, Emily A.; Gevensleben, Heidrun; Goltz, Diane; Dröge, F; Franzen, Alina; Dietrich, Jörn; Kristiansen, Glen; Bootz, Friedrich; Schröck, Andreas; Dietrich, Dimo

doi:10.1186/s13148-017-0317-7

Cited by 15 publications

(16 citation statements)

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“…Head and neck squamous cell carcinoma (HNSCC) is a heterogeneous group of epithelial tumors that describe approximately 90% of the malignant neoplasms occurring in the oral cavity, oropharynx, hypopharynx and larynx (Pai and Westra, 2009;Hussein et al, 2017). Oral and oro-in tumors with similar clinical parameters, leading to different prognostic expectations (Colacino et al, 2013;Lechner et al, 2013;Erhart et al, 2016;Sailer et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

“…A common etiological factor in HNSCC is prolonged and excessive alcohol and tobacco consumption which establish a synergistic, dose-dependent relationship between them ( Polanska et al , 2014 ). The infection by high-risk Human papillomavirus (HPV) has been particularly associated with oropharyngeal cancer ( Lechner et al , 2013 ; D'Souza and Saranath, 2015 ; Sailer et al , 2017 ). HPV positive and HPV negative tumors have a distinct molecular profile, even in tumors with similar clinical parameters, leading to different prognostic expectations ( Colacino et al , 2013 ; Lechner et al , 2013 ; Erhart et al , 2016 ; Sailer et al , 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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Hypermethylation status of DAPK, MGMT and RUNX3 in HPV negative oral and oropharyngeal squamous cell carcinoma

et al. 2020

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Squamous cell carcinoma of the oral cavity and oropharynx is the sixth most common type of cancer in the world. During tumorigenesis, gene promoter hypermethylation is considered an important mechanism of transcription silencing of tumor suppressor genes, such as DAPK, MGMT and RUNX3. These genes participate in signaling pathways related to apoptosis, DNA repair and proliferation whose loss of expression is possibly associated with cancer development and progression. In order to investigate associations between hypermethylation and clinicopathological and prognostic parameters, promoter methylation was evaluated in 72 HPV negative oral and oropharyngeal tumors using methylation-specific PCR. Hypermethylation frequencies found for DAPK, MGMT and RUNX3 were 38.88%, 19.44% and 1.38% respectively. Patients with MGMT hypermethylation had a better 2-year overall survival compared to patients without methylation. Being MGMT a repair gene for alkylating agents, it could be a biomarker of treatment response for patients who are candidates for cisplatin chemotherapy, predicting drug resistance. In view of the considerable levels of hypermethylation in cancer cells and, for MGMT, its prognostic relevance, DAPK and MGMT show potential as epigenetic markers, in a way that additional studies may test its viability and efficacy in clinical management.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hypermethylation status of DAPK, MGMT and RUNX3 in HPV negative oral and oropharyngeal squamous cell carcinoma

et al. 2020

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“…Loss of ONECUT1 expression revealed a key role in human pancreatic cancer cells [28]. PITX3 DNA methylation functioned as an independent biomarker for predicting the overall survival of patients with head and neck squamous cell carcinoma [29]. TRAF6 enhanced the progression and growth of colorectal cancer by nuclear shuttle regulation NF-kB/c-jun signaling pathway [30].…”

Section: Discussionmentioning

confidence: 99%

A 14 transcription factors-associated nomogram predicts the recurrence-free survival of gastric cancer

Ma¹,

Chen

Yang

et al. 2020

Preprint

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Background: We aimed to construct and validate a novel transcription factors (TFs) signature for the prediction of gastric cancer (GC) patient’s recurrence-free survival (RFS) from TCGA and Gene Expression Omnibus (GEO) database and improve the predictive ability of RFS in GC patients.Methods: We searched TCGA database and GEO database to obtain gene expression data and related clinical information for GC. In total, 722 TFs and 384 GC patients with intact clinical information were identified to develop a novel TF signature. All TFs were included in a univariate Cox regression model. We then used the least absolute shrinkage and selection operator (LASSO) Cox regression model which included only TFs with P < 0.05 in the univariate model to identify candidate TFs related to RFS. After further adjustment, multivariate Cox regression was performed based on the candidate TFs for the identification of TF signatures in the RFS evaluation of GC patients.Results: We successfully confirmed the high ability of the 14-TF panel for predicting GC patients’ RFS by receiver operating characteristic (ROC). AUCs at 1, 3, 5 years in internal validation dataset were 0.827, 0.817, 0.811, respectively. Some similar results were calculated in external validation dataset (0.808, 0.907, 0.813, respectively) and entire dataset (0.815, 0.849, 0.801, respectively). Besides, our model makes a good distinction between the high-risk group and the low-risk group. Furthermore, a nomogram was developed via risk score, sex, cancer status and tumor grade, and C-index, ROC, the calibration plots as well as decision curve analysis (DCA) demonstrated good ability and clinical application of the nomogram.Conclusions: We successfully established and validated a novel 14-TF-associated nomogram for predicting the RFS of GC.

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“…Cancer involves a complex regulatory network, integrating multiple biomarkers into an aggregated model could improve prognostic value compared with single biomarker [ 37 ]. The biomarkers discovery for OSCC have been reported in several studies [ 38 , 39 ], but few of them used more than two datasets or explore the biomarkers across different omics. In this study, we developed an OSCC prognostic classifier model that includes seven CpG sites and validated the model using two independent external datasets.…”

Section: Discussionmentioning

confidence: 99%

Seven-CpG-based prognostic signature coupled with gene expression predicts survival of oral squamous cell carcinoma

et al. 2017

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BackgroundDNA methylation has started a recent revolution in genomics biology by identifying key biomarkers for multiple cancers, including oral squamous cell carcinoma (OSCC), the most common head and neck squamous cell carcinoma.MethodsA multi-stage screening strategy was used to identify DNA-methylation-based signatures for OSCC prognosis. We used The Cancer Genome Atlas (TCGA) data as training set which were validated in two independent datasets from Gene Expression Omnibus (GEO). The correlation between DNA methylation and corresponding gene expression and the prognostic value of the gene expression were explored as well.ResultsThe seven DNA methylation CpG sites were identified which were significantly associated with OSCC overall survival. Prognostic signature, a weighted linear combination of the seven CpG sites, successfully distinguished the overall survival of OSCC patients and had a moderate predictive ability for survival [training set: hazard ratio (HR) = 3.23, P = 5.52 × 10−10, area under the curve (AUC) = 0.76; validation set 1: HR = 2.79, P = 0.010, AUC = 0.67; validation set 2: HR = 3.69, P = 0.011, AUC = 0.66]. Stratification analysis by human papillomavirus status, clinical stage, age, gender, smoking status, and grade retained statistical significance. Expression of genes corresponding to candidate CpG sites (AJAP1, SHANK2, FOXA2, MT1A, ZNF570, HOXC4, and HOXB4) was also significantly associated with patient’s survival. Signature integrating of DNA methylation, gene expression, and clinical information showed a superior ability for prognostic prediction (AUC = 0.78).ConclusionPrognostic signature integrated of DNA methylation, gene expression, and clinical information provides a better prognostic prediction value for OSCC patients than that with clinical information only.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-017-0392-9) contains supplementary material, which is available to authorized users.

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PITX3 DNA methylation is an independent predictor of overall survival in patients with head and neck squamous cell carcinoma

Cited by 15 publications

References 46 publications

Hypermethylation status of DAPK, MGMT and RUNX3 in HPV negative oral and oropharyngeal squamous cell carcinoma

Hypermethylation status of DAPK, MGMT and RUNX3 in HPV negative oral and oropharyngeal squamous cell carcinoma

A 14 transcription factors-associated nomogram predicts the recurrence-free survival of gastric cancer

Seven-CpG-based prognostic signature coupled with gene expression predicts survival of oral squamous cell carcinoma

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