The clinical significance of <i>HOXA9 </i>promoter hypermethylation in head and neck squamous cell carcinoma

Zhou, Chongchang; Li, Jinyun; Li, Qun; Liu, Huigao; Ye, Dong; Wu, Zhenhua; Shen, Zhisen; Deng, Hongxia

doi:10.1002/jcla.22873

Cited by 15 publications

(7 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Abnormal expression of HOXA9 is associated with the occurrence of a variety of cancers [20][21][22]. Several recent studies have shown that hypermethylation of the HOXA9 promoter causes transcriptional inactivation in many malignant tumors [23][24][25]. In our study, INHBB and HOXA9 were hypermethylated in patients with obesity.…”

Section: Discussionsupporting

confidence: 56%

Analysis of genome-wide DNA methylation patterns in obesity

Chun-hu

Wang

2021

Endocr J

View full text Add to dashboard Cite

Obesity is a chronic and complex psychosomatic disease that is becoming increasingly prevalent worldwide. This study aimed to analyze whole methylation profiles to uncover the epigenetic mechanisms associated with obesity. DNA methylation profiles in blood samples from patients with obesity and normal controls were studied using the Illumina 850 K methylation microarray. The diagnostic value of the differentially methylated genes was determined using receiver operating characteristic (ROC) analysis. The expression of selected candidate genes was verified using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and pyrosequencing. A total of 9,371 significantly differentially methylated sites (7,974 hypermethylated sites and 1,397 hypomethylated sites) were identified in 4,571 genes. A difference in the distribution of differentially methylated sites (hypermethylated and hypomethylated) in both gene structures and CpG islands was observed. A total of 114 key differentially methylated sites were identified in the CpG islands. ROC results indicated that Inhibin Subunit Beta B (INHBB), Homeobox A9 (HOXA9), Troponin T3 (TNNT3), Cyclic adenosine monophosphate (cAMP)responsive element binding protein (CREB)-regulated transcription coactivator 1 (CRTC1) and Zinc finger and BTB domaincontaining 7 B (ZBTB7B) could discriminate patients with obesity from normal controls. RT-qPCR results of CRTC1 and ZBTB7B were consistent with our methylation profile results. The pyrosequencing results showed that the methylation levels of CRTC1 CpG sites (CpG1 and CpG2-cg11660071) and INHBB CpG sites (CpG2) were significantly changed in patients with obesity compared with normal controls, which was consistent with our DNA methylation profile results. Our study provides new insights into the pathological mechanism of obesity.

show abstract

Section: Discussionsupporting

confidence: 56%

Analysis of genome-wide DNA methylation patterns in obesity

Chun-hu

Wang

2021

Endocr J

View full text Add to dashboard Cite

show abstract

“…We may conclude that the difference in the DNA methylation pattern of a significant number of genes that we described should be discriminative enough for diagnostics of SE versus NS similar to that recently proposed for lung adenocarcinoma where the methylation in HOXA9 was upregulated in contrast to its downregulation in other three genes [ 56 ]. Importantly, microRNAs of the miR-371-373 cluster that were found in patients with germ cell tumors (GTCs) and even in experimental teratomas derived from human genetically modified stem cells in the teratoma assay that should be devoted not only to the confirmation of pluripotency but also to the possible malignancy of such cells [ 57 , 58 ] have lately been intensively investigated for liquid biopsies and early diagnostics of TGCT, but they do not discriminate between SE and NS as did our results with promoter methylation.…”

Section: Discussionsupporting

confidence: 74%

In Search of TGCT Biomarkers: A Comprehensive In Silico and Histopathological Analysis

et al. 2020

View full text Add to dashboard Cite

Testicular germ cell tumors (TGCTs) are ever more affecting the young male population. Germ cell neoplasia in situ (GCNIS) is the origin of TGCTs, namely, seminomas (SE) and a heterogeneous group of nonseminomas (NS) comprising embryonal carcinoma, teratoma, yolk sac tumor, and choriocarcinoma. Response to the treatment and prognosis, especially of NS, depend on precise diagnosis with a necessity for discovery of new biomarkers. We aimed to perform comprehensive in silico analysis at the DNA, RNA, and protein levels of six prospective (HOXA9, MGMT, CFC1, PRSS21, RASSF1A, and MAGEC2) and six known TGCT biomarkers (OCT4, SOX17, SOX2, SALL4, NANOG, and KIT) and assess its congruence with histopathological analysis in all forms of TGCTs. Cancer Hallmarks Analytics Tool, the Search Tool for the Retrieval of Interacting Genes/Proteins database, and UALCAN, an interactive web resource for analyzing cancer OMICS data, were used. In 108 TGCT and 48 tumor-free testicular samples, the immunoreactivity score (IRS) was calculated. SE showed higher frequency in DNA alteration, while DNA methylation was significantly higher for all prospective biomarkers in NS. In GCNIS, we assessed the clinical positivity of RASSF1 and PRSS21 in 52% and 62% of samples, respectively, in contrast to low or nil positivity in healthy seminiferous tubules, TGTCs as a group, SE, NS, or all NS components. Although present in approximately 80% of healthy seminiferous tubules (HT) and GCNIS, HOXA9 was diagnostically positive in 64% of TGCTs, while it was positive in 82% of NS versus 29% of SE. Results at the DNA, mRNA, and protein levels on putative and already known biomarkers were included in the suggested panels that may prove to be important for better diagnostics of various forms of TGCTs.

show abstract

“…Among HOXB genes, HOXB13 is frequently identified as being hypermethylated in tumors. Its promoter methylation is a candidate biomarker for gastric [64] and endometrial tumors with enhanced invasiveness [114]. The hypermethylation of HOXB13 also occurs in nearly 30% of renal cell carcinomas, as the silencing of this gene is associated with apoptosis ratio decrease, tumor grade increase and microvessels invasion [61].…”

Section: Hoxb and Hoxc Genes Methylated In Cancermentioning

confidence: 99%

Methylation in HOX Clusters and Its Applications in Cancer Therapy

Paço¹,

Garcia

Freitas

2020

Cells

View full text Add to dashboard Cite

HOX genes are commonly known for their role in embryonic development, defining the positional identity of most structures along the anterior–posterior axis. In postembryonic life, HOX gene aberrant expression can affect several processes involved in tumorigenesis such as proliferation, apoptosis, migration and invasion. Epigenetic modifications are implicated in gene expression deregulation, and it is accepted that methylation events affecting HOX gene expression play crucial roles in tumorigenesis. In fact, specific methylation profiles in the HOX gene sequence or in HOX-associated histones are recognized as potential biomarkers in several cancers, helping in the prediction of disease outcomes and adding information for decisions regarding the patient’s treatment. The methylation of some HOX genes can be associated with chemotherapy resistance, and its identification may suggest the use of other treatment options. The use of epigenetic drugs affecting generalized or specific DNA methylation profiles, an approach that now deserves much attention, seems likely to be a promising weapon in cancer therapy in the near future. In this review, we summarize these topics, focusing particularly on how the regulation of epigenetic processes may be used in cancer therapy.

show abstract

The clinical significance of HOXA9 promoter hypermethylation in head and neck squamous cell carcinoma

Cited by 15 publications

References 49 publications

Analysis of genome-wide DNA methylation patterns in obesity

Analysis of genome-wide DNA methylation patterns in obesity

In Search of TGCT Biomarkers: A Comprehensive In Silico and Histopathological Analysis

Methylation in HOX Clusters and Its Applications in Cancer Therapy

Contact Info

Product

Resources

About