<i>IGSF4</i>Methylation as an Independent Marker of Human Papillomavirus–Positive Oropharyngeal Squamous Cell Carcinoma

Chen, Kang Mei; Stephen, Josena K.; Havard, Shaleta; Mahan, Meredith; Divine, George; Worsham, Maria J.

doi:10.1001/jamaoto.2014.3393

Cited by 15 publications

(10 citation statements)

References 42 publications

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“…This is the first attempt to characterize the composition of OPSCC tumor tissue by trace elements using XFM and to demonstrate that Zn-binding protein AZGP1 is a potential biomarker for positive prognosis in HNSCC. Our findings add to other work that also demonstrates that patient outcome in HPV-positive OPSCC is affected by variables such as smoking status, hormonal status, gene expression and methylation patterns and HPV integration status 4,7,8,28 .…”

Section: Discussionsupporting

confidence: 80%

“…Immune-related tumor-extrinsic variables have been identified in HPV-positive OPSCC, including some by our group 5,6 , such as the phenotypic and morphologic features of tumor infiltrating lymphocytes. With regards to tumor-intrinsic variables, sex hormone overexpression and gene silencing through promoter methylation 7,8 have recently been correlated to improved survival in HPV-positive OPSCC.…”

Section: Introductionmentioning

confidence: 99%

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Elemental Zn and its Binding Protein Zinc-α2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma

Poropatich

Paunesku

Zander

et al. 2019

Sci Rep

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Human papillomavirus (HPV)-positive head and neck squamous cell carcinoma (HNSCC) is biologically distinct from HPV-negative HNSCC. Outside of HPV-status, few tumor-intrinsic variables have been identified that correlate to improved survival. As part of exploratory analysis into the trace elemental composition of oropharyngeal squamous cell carcinoma (OPSCC), we performed elemental quanitification by X-ray fluorescence microscopy (XFM) on a small cohort (n = 32) of patients with HPV-positive and -negative OPSCC and identified in HPV-positive cases increased zinc (Zn) concentrations in tumor tissue relative to normal tissue. Subsequent immunohistochemistry of six Zn-binding proteins—zinc-α2-glycoprotein (AZGP1), Lipocalin-1, Albumin, S100A7, S100A8 and S100A9—revealed that only AZGP1 expression significantly correlated to HPV-status (p < 0.001) and was also increased in tumor relative to normal tissue from HPV-positive OPSCC tumor samples. AZGP1 protein expression in our cohort significantly correlated to a prolonged recurrence-free survival (p = 0.029), similar to HNSCC cases from the TCGA (n = 499), where highest AZGP1 mRNA levels correlated to improved overall survival (p = 0.023). By showing for the first time that HPV-positive OPSCC patients have increased intratumoral Zn levels and AZGP1 expression, we identify possible positive prognostic biomarkers in HNSCC as well as possible mechanisms of increased sensitivity to chemoradiation in HPV-positive OPSCC.

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Section: Discussionsupporting

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Elemental Zn and its Binding Protein Zinc-α2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma

Poropatich

Paunesku

Zander

et al. 2019

Sci Rep

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“…This SNP lies in an intergenic region 515 kb upstream of CADM1 , which encodes a single-pass transmembrane protein involved in cell–cell adhesion and signal transduction 18 19 20 . CADM1 is also a putative tumour suppressor in many human carcinomas, including SCC, as it is frequently downregulated in these tissues via promoter methylation 21 22 23 . Notably, CADM1 expression levels are associated with survival in SCC patients.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma

et al. 2016

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Cutaneous squamous cell carcinoma represents the second most common cutaneous malignancy, affecting 7–11% of Caucasians in the United States. The genetic determinants of susceptibility to cutaneous squamous cell carcinoma remain largely unknown. Here we report the results of a two-stage genome-wide association study of cutaneous squamous cell carcinoma, totalling 7,404 cases and 292,076 controls. Eleven loci reached genome-wide significance (P<5 × 10−8) including seven previously confirmed pigmentation-related loci: MC1R, ASIP, TYR, SLC45A2, OCA2, IRF4 and BNC2. We identify an additional four susceptibility loci: 11q23.3 CADM1, a metastasis suppressor gene involved in modifying tumour interaction with cell-mediated immunity; 2p22.3; 7p21.1 AHR, the dioxin receptor involved in anti-apoptotic pathways and melanoma progression; and 9q34.3 SEC16A, a putative oncogene with roles in secretion and cellular proliferation. These susceptibility loci provide deeper insight into the pathogenesis of squamous cell carcinoma.

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“…After a median follow-up of 2.97 years, the patients with a high methylation level of miR-124a-3 were shown to develop metachronous gastric cancers with a statistically higher incidence (hazard ratio = 2.3, p = 0.042). In addition, several promising DNA methylation markers have been identified through retrospective cohort studies [ 131 – 133 ].…”

Section: Implications For Cancer Prevention Diagnosis and Therapymentioning

confidence: 99%

Epigenetic impact of infection on carcinogenesis: mechanisms and applications

Hattori¹,

Ushijima²

2016

Genome Med

113

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Viral and bacterial infections are involved in the development of human cancers, such as liver, nasopharyngeal, cervical, head and neck, and gastric cancers. Aberrant DNA methylation is frequently present in these cancers, and some of the aberrantly methylated genes are causally involved in cancer development and progression. Notably, aberrant DNA methylation can be present even in non-cancerous or precancerous tissues, and its levels correlate with the risk of cancer development, producing a so-called ‘epigenetic field for cancerization’. Mechanistically, most viral or bacterial infections induce DNA methylation indirectly via chronic inflammation, but recent studies have indicated that some viruses have direct effects on the epigenetic machinery of host cells. From a translational viewpoint, a recent multicenter prospective cohort study demonstrated that assessment of the extent of alterations in DNA methylation in non-cancerous tissues can be used to predict cancer risk. Furthermore, suppression of aberrant DNA methylation was shown to be a useful strategy for cancer prevention in an animal model. Here, we review the involvement of aberrant DNA methylation in various types of infection-associated cancers, along with individual induction mechanisms, and we discuss the application of these findings for cancer prevention, diagnosis, and therapy.

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IGSF4Methylation as an Independent Marker of Human Papillomavirus–Positive Oropharyngeal Squamous Cell Carcinoma

Abstract: Methylation of IGSF4 is an independent predictor of HPV-positive status. DNA methylation in conjunction with HPV infection appears to play a role in OPSCC.

Cited by 15 publications

References 42 publications

Elemental Zn and its Binding Protein Zinc-α2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma

Elemental Zn and its Binding Protein Zinc-α2-Glycoprotein are Elevated in HPV-Positive Oropharyngeal Squamous Cell Carcinoma

Genome-wide association study identifies novel susceptibility loci for cutaneous squamous cell carcinoma

Epigenetic impact of infection on carcinogenesis: mechanisms and applications

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