Candidate Biomarkers for HPV‐Negative Head and Neck Cancer Identified via Gene Expression Barcode Analysis

Yang, Shiayin F.; Bier‐Laning, Carol M.; Adams, William; Zilliox, Michael J.

doi:10.1177/0194599816642436

Cited by 5 publications

(4 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As yet, only few prognostic biomarkers have been investigated in this patient cohort. For example, in silico analysis of expression data deposited in the Gene Expression Omnibus (GEO) identified spectrin, a cytoskleton protein, as a promising new biomarker [ 48 ]. Expression of the tyrosine kinase c-MET has been shown to be prognostic in oral squamous cell cancer, which is in general not associated with HPV-infection [ 49 ].…”

Section: Discussionmentioning

confidence: 99%

Intragenic DNA methylation of PITX1 and the adjacent long non-coding RNA C5orf66-AS1 are prognostic biomarkers in patients with head and neck squamous cell carcinomas

et al. 2018

View full text Add to dashboard Cite

BackgroundPatients with squamous cell cancer of the head and neck region (HNSCC) are at risk for disease recurrence and metastases, even after initial successful therapy. A tissue-based biomarker could be beneficial to guide treatment as well as post-treatment surveillance. Gene methylation status has been recently identified as powerful prognostic biomarker in HNSCC. We therefore evaluated the methylation status of the homeobox gene PITX1 and the adjacent long intergenic non-coding RNA (lincRNA) C5orf66-AS1 in publicly available datasets.MethodsGene methylation and expression data from 528 patients with HNSCC included in The Cancer Genome Atlas (TCGA, there obtained by using the Infinium HumanMethylation450 BeadChip Kit) were evaluated and methylation and expression levels of PITX1 and lincRNA C5orf66-AS1 was correlated with overall survival and other parameters. Thus, ten beads targeting PITX1 exon 3 and three beads targeting lincRNA C5orf66-AS1 were identified as significant candidates. The mean methylation of these beads was used for further correlation and the median was employed for dichotomization.ResultsBoth PITX1 exon 3 and lincRNA C5orf66-AS1 were significantly higher methylated in tumor tissue than in normal adjacent tissue (NAT) (PITX1 exon 3: tumor tissue 58.1%, NAT: 31.7%, p<0.001; lincRNA C5orf66-AS1: tumor tissue: 27.4%, NAT: 18.9%, p<0.001). In a univariate analysis, hypermethylation of both loci was significantly associated with the risk of death (univariate: exon 3: Hazard ratio (HR): 4.97 [1.78–16.71], p = 0.010, lincRNA C5orf66-AS1: Hazard ratio (HR): 12.23 [3.01–49.74], p<0.001). PITX1 exon 3 and lincRNA C5orf66-AS1 methylation was also significantly correlated with tumor localization, T category, human papilloma virus (HPV)-negative and p16-negative tumors and tumor grade. Kaplan-Meier analysis showed, that lincRNA C5orf66-AS1 hypomethylation was significantly associated with overall survival (p = 0.001) in the entire cohort as well in a subgroup of HPV-negative tumors (p = 0.003) and in patients with laryngeal tumors (p = 0.022).ConclusionMethylation status of PITX1 and even more so of lincRNA C5orf66-AS1 is a promising prognostic biomarker in HNSCC, in particular for HPV-negative patients. Further prospective evaluation is warranted.

show abstract

Section: Discussionmentioning

confidence: 99%

Intragenic DNA methylation of PITX1 and the adjacent long non-coding RNA C5orf66-AS1 are prognostic biomarkers in patients with head and neck squamous cell carcinomas

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The mutation of SPTBN1 is closely related to the occurrence of OPSCC 103 , but the specific molecular mechanism of this change is not clear. Another HPV-negative study of OPSCC demonstrated that spectrins are significantly related to poor prognosis 104 . Collectively, these studies increase the possibility that SPTBN1 is a useful biomarker in OPSCC, but further research is required to clarify this suggestion.…”

Section: βIi Spectrin In Head and Neck Diseasementioning

confidence: 99%

βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases

Yang¹,

Yang²,

Sun³

et al. 2021

Int. J. Biol. Sci.

View full text Add to dashboard Cite

βII spectrin, the most common isoform of non-erythrocyte spectrin, is a cytoskeleton protein present in all nucleated cells. Interestingly, βII spectrin is essential for the development of various organs such as nerve, epithelium, inner ear, liver and heart. The functions of βII spectrin include not only establishing and maintaining the cell structure but also regulating a variety of cellular functions, such as cell apoptosis, cell adhesion, cell spreading and cell cycle regulation. Notably, βII spectrin dysfunction is associated with embryonic lethality and the DNA damage response. More recently, the detection of altered βII spectrin expression in tumors indicated that βII spectrin might be involved in the development and progression of cancer. Its mutations and disorders could result in developmental disabilities and various diseases. The versatile roles of βII spectrin in disease have been examined in an increasing number of studies; nonetheless, the exact mechanisms of βII spectrin are still poorly understood. Thus, we summarize the structural features and biological roles of βII spectrin and discuss its molecular mechanisms and functions in development, homeostasis, regeneration and differentiation. This review highlight the potential effects of βII spectrin dysfunction in cancer and other diseases, outstanding questions for the future investigation of therapeutic targets. The investigation of the regulatory mechanism of βII spectrin signal inactivation and recovery may bring hope for future therapy of related diseases.

show abstract

“…Besides, spectrin family was the most detected and identified in cells transfected with UNC5B truncates. In view of the reports of spectrin in impacting tumour development and aggressiveness, [44][45][46][47] the binding of spectrin family to the intracellular domain of UNC5B was also considered to be closely related to the metastasis of BC cells.…”

Section: Discussionmentioning

confidence: 99%

The intracellular domain of UNC5B facilities proliferation and metastasis of bladder cancer cells

Huang

Zhang

Miao

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

The intracellular domain of UNC5B contains both death domain and caspase‐3 cleavage site, and is regarded as a functional domain that mediates apoptosis. However, in our previous studies, we found that the death domain of UNC5B in bladder cancer cells could not be activated to promote apoptosis. In this study, different UNC5B truncates (residue 399‐945, residue 412‐945) were created to explore whether the caspase‐3 cleavage site (site 412), as another potential functional domain of its intracellular portion, could be activated to induce apoptosis in bladder cancer cells. Using mass spectrometry, we acquired a comprehensive and detailed identification of differentially expressed proteins by overexpressing UNC5B and its truncates. Protein‐protein‐interaction (PPI) network analysis was also applied to investigate the aggregation of related proteins and predict the functional changes. EDU assay, apoptosis, xenograft tumour implantation, migration, invasion and tumour metastasis were performed to comprehensively identify the effects of UNC5B truncates on bladder cancer cells. We demonstrate that the intracellular domain of UNC5B promotes cell proliferation in vitro and tumour formation in vivo, by binding to a large number of ribosomal proteins. The overexpression of intracellular domain also facilitates cells to migrate, invade and metastasize by interacting with fibronectin, beta‐catenin and vimentin. In addition, we reveal that overexpressing the intracellular domain of UNC5B cannot bind or activate cleaved caspase‐3 to trigger apoptosis in bladder cancer cells.

show abstract

Candidate Biomarkers for HPV‐Negative Head and Neck Cancer Identified via Gene Expression Barcode Analysis

Abstract: Our analysis of public genomic data shows promise in identifying biomarkers that may allow clinicians to make more accurate survival predictions. Spectrin is a strong candidate for further biomarker testing.

Cited by 5 publications

References 29 publications

Intragenic DNA methylation of PITX1 and the adjacent long non-coding RNA C5orf66-AS1 are prognostic biomarkers in patients with head and neck squamous cell carcinomas

Intragenic DNA methylation of PITX1 and the adjacent long non-coding RNA C5orf66-AS1 are prognostic biomarkers in patients with head and neck squamous cell carcinomas

βII spectrin (SPTBN1): biological function and clinical potential in cancer and other diseases

The intracellular domain of UNC5B facilities proliferation and metastasis of bladder cancer cells

Contact Info

Product

Resources

About