WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers - a short report

Ribeiro, Ilda Patrícia; Caramelo, Francisco; Marques, Francisco Batel; Domingues, Ana Patrícia; Mesquita, Margarida; Barroso, Leonor; Prazeres, Hugo; Julião, Maria José; Baptista, Isabel; Ferreira, Artur; Melo, Joana Barbosa; Carreira, Isabel M.

doi:10.1007/s13402-016-0293-5

Cited by 33 publications

(25 citation statements)

References 31 publications

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“…The survival difference between the two identified clusters, cluster 4 vs. cluster 6, represented a clear difference in the lifetime of these patients. These results fall in agreement with previous reports that showed a significant association between promoter methylation status and worse OSCC patients' survival [31][32][33][34]. These results demonstrated the utility of epigenetic alterations detection for potential clinical application in OSCC patients.…”

Section: Discussionsupporting

confidence: 93%

Epigenetic Alterations Associated with the Overall Survival and Recurrence Free Survival among Oral Squamous Cell Carcinoma Patients

Ghantous

Nashef

Abu-El-Naaj

2020

JCM

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Oral squamous cell carcinoma (OSCC) is a fatal disease caused by complex interactions between environmental, genomic, and epigenetic alterations. In the current study, we aimed to identify clusters of genes whose promoter methylation status correlated with various tested clinical features. Molecular datasets of genetic and methylation analysis based on whole-genome sequencing of 159 OSCC patients were obtained from the The Cancer Genome Atlas (TCGA) data portal. Genes were clustered based on their methylation status and were tested for their association with demographic, pathological, and clinical features of the patients. Overall, seven clusters of genes were revealed that showed a significant association with the overall survival/recurrence free survival of patients. The top ranked genes within cluster 4, which showed the worst prognosis, primarily acted as paraneoplastic genes, while the genes within cluster 6 primarily acted as anti-tumor genes. A significant difference was found regarding the mean age in the different clusters. No significant correlation was found between the tumor staging and the different clusters. In conclusion, our result provided a proof-of-principle for the existence of phenotypic diversity among the epigenetic clusters of OSCC and demonstrated the utility of the use epigenetics alterations in devolving new prognostic and therapeutics tools for OSCC patients.

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Section: Discussionsupporting

confidence: 93%

Epigenetic Alterations Associated with the Overall Survival and Recurrence Free Survival among Oral Squamous Cell Carcinoma Patients

Ghantous

Nashef

Abu-El-Naaj

2020

JCM

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“…Dysregulated expression of PAX5 is involved in differentiation block (55), somatic hypermutation and immunoglobulin heavy chain class switch recombination (56), leukemogenesis (57), and positive regulation of c-Met transcription (58). PAX5 association to different tumor types suggests it has diagnostic or prognostic utility in lung cancer (59), Hodgkin lymphoma (60), acute lymphocytic leukemia (61), breast cancer (61), oral cancer (62,63), gastric cancer (64), head and neck cancer (65,66), and esophageal cancer (66). A recent study demonstrated that the lack of expression of PAX5 in lymphoid neoplasms is associated with promoter hypermethylation, leading to PAX5 silencing in cases characterized by poor clinical outcome (67).…”

Section: Discussionmentioning

confidence: 99%

JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients

Guerrero-Preston

Lawson

Rodríguez‐Torres

et al. 2019

Cancer Prevention Research

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To inform novel personalized medicine approaches for race and socioeconomic disparities in head and neck cancer, we examined germline and somatic mutations, immune signatures, and epigenetic alterations linked to neighborhood determinants of health in Black and non-Latino White (NLW) patients with head and neck cancer. Cox proportional hazards revealed that Black patients with squamous cell carcinoma of head and neck (HNSCC) with PAX5 (P ¼ 0.06) and PAX1 (P ¼ 0.017) promoter methylation had worse survival than NLW patients, after controlling for education, zipcode, and tumor-node-metastasis stage (n ¼ 118). We also found that promoter methylation of PAX1 and PAX5 (n ¼ 78), was correlated with neighborhood characteristics at the zip-code level (P < 0.05).Analyses also showed differences in the frequency of TP53 mutations (n ¼ 32) and tumor-infiltrating lymphocyte (TIL) counts (n ¼ 24), and the presence of a specific C ! A germline mutation in JAK3, chr19:17954215 (protein P132T), in Black patients with HNSCC (n ¼ 73; P < 0.05), when compared with NLW (n ¼ 37) patients. TIL counts are associated (P ¼ 0.035) with long-term (>5 years), when compared with short-term survival (<2 years). We show bio-social determinants of health associated with survival in Black patients with HNSCC, which together with racial differences shown in germline mutations, somatic mutations, and TIL counts, suggests that contextual factors may significantly inform precision oncology services for diverse populations. A, Molecular markers, combined with external and internal environment variables, can be used as biosocial markers of head and neck cancer outcome disparities, head and neck cancer markers, and precision medicine markers for patients with head and neck cancer. B, Shows that PAX5 methylation levels inversely correlate (r ¼ À0.83) with TIL counts in patients with HNSCC. C, Shows that JAK3 expression in Black patients with HNSCC differs by anatomic location. D, Shows that Notch1 mutations and PAX1 methylation levels also differ by anatomic location and race in patients with HNSCC.

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“…MS-MLPA analyses were performed using MS-MLPA probe set ME002 (MRC-Holland), which can simultaneously detect CNAs in 38 tumor suppressor genes and aberrant methylation patterns in a subset of 25 of these genes. All MS-MLPA reactions were performed according our previous work (11,12). Three controls selected from the previously analyzed control group, without CNAs and methylation values below 20%, as well as a negative control (without DNA), were always included in each MS-MLPA assay.…”

Section: Methodsmentioning

confidence: 99%

Upper aerodigestive tract carcinoma: Development of a (epi)genomic predictive model for recurrence and metastasis

et al. 2020

Self Cite

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Despite the increased molecular knowledge and the diagnostic and therapeutic improvements, the survival of patients with upper aerodigestive tract carcinoma remains poor. The identification of early diagnostic and prognostic biomarkers and the development of molecular models to distinguish patients that will recur and/or develop metastasis after treatment as well as to benefit with target therapies can be important to decrease mortality, improve survival rates and improve the quality of life of these patients. The current study analyzed 21 upper aerodigestive tract carcinomas through array comparative genomic hybridization and methylation-specific multiplex ligation-dependent probe amplification techniques. A number of chromosomal regions and genes were observed with copy number alterations and methylation. A predictive (epi)genomic model that comprises the 3p chromosomal region and WT1, VHL and THBS1 genes was built, highlighting a molecular signature with possible clinical use. The current study may aid in the development of a more individualized patient management and targeted drug design. The power of this genomic and epigenetic model to predict the recurrence and metastasis development should be evaluated and validated in future larger cohort study.

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WT1, MSH6, GATA5 and PAX5 as epigenetic oral squamous cell carcinoma biomarkers - a short report

Abstract: Our data highlight the importance of epigenetically assessing OSCCs to identify key genes that may serve as diagnostic and prognostic biomarkers and, potentially, as candidate therapeutic targets.

Cited by 33 publications

References 31 publications

Epigenetic Alterations Associated with the Overall Survival and Recurrence Free Survival among Oral Squamous Cell Carcinoma Patients

Epigenetic Alterations Associated with the Overall Survival and Recurrence Free Survival among Oral Squamous Cell Carcinoma Patients

JAK3 Variant, Immune Signatures, DNA Methylation, and Social Determinants Linked to Survival Racial Disparities in Head and Neck Cancer Patients

Upper aerodigestive tract carcinoma: Development of a (epi)genomic predictive model for recurrence and metastasis

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