Overexpression of EGFR in Oral Premalignant Lesions and OSCC and Its Impact on Survival and Recurrence

Mirza, Yumna; Ali, Saleema Mehboob; Awan, M. S.; Idress, Romana; Naeem, Syed; Zahid, Nida; Qadeer, Urooj

doi:10.7150/oncm.22614

Cited by 9 publications

(10 citation statements)

References 36 publications

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“…EGFR has been earlier implicated in progression, recurrence, and stemness of oral cancer [42,43]. EGFR is inappropriately activated in cancer mainly because of amplification and point mutations.…”

Section: Discussionmentioning

confidence: 99%

Application of Random Forest and data integration identifies three dysregulated genes and enrichment of Central Carbon Metabolism pathway in Oral Cancer

et al. 2020

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Background Studies of epigenomic alterations associated with diseases primarily focus on methylation profiles of promoter regions of genes, but not of other genomic regions. In our past work (Das et al. 2019) on patients suffering from gingivo-buccal oral cancer – the most prevalent form of cancer among males in India – we have also focused on promoter methylation changes and resultant impact on transcription profiles. Here, we have investigated alterations in non-promoter (gene-body) methylation profiles and have carried out an integrative analysis of gene-body methylation and transcriptomic data of oral cancer patients. Methods Tumor and adjacent normal tissue samples were collected from 40 patients. Data on methylation in the non-promoter (gene-body) regions of genes and transcriptome profiles were generated and analyzed. Because of high dimensionality and highly correlated nature of these data, we have used Random Forest (RF) and other data-analytical methods. Results Integrative analysis of non-promoter methylation and transcriptome data revealed significant methylation-driven alterations in some genes that also significantly impact on their transcription levels. These changes result in enrichment of the Central Carbon Metabolism (CCM) pathway, primarily by dysregulation of (a) NTRK3, which plays a dual role as an oncogene and a tumor suppressor; (b) SLC7A5 (LAT1) which is a transporter dedicated to essential amino acids, and is overexpressed in cancer cells to meet the increased demand for nutrients that include glucose and essential amino acids; and, (c) EGFR which has been earlier implicated in progression, recurrence, and stemness of oral cancer, but we provide evidence of epigenetic impact on overexpression of this gene for the first time. Conclusions In rapidly dividing cancer cells, metabolic reprogramming from normal cells takes place to enable enhanced proliferation. Here, we have identified that among oral cancer patients, genes in the CCM pathway – that plays a fundamental role in metabolic reprogramming – are significantly dysregulated because of perturbation of methylation in non-promoter regions of the genome. This result compliments our previous result that perturbation of promoter methylation results in significant changes in key genes that regulate the feedback process of DNA methylation for the maintenance of normal cell division.

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Section: Discussionmentioning

confidence: 99%

Application of Random Forest and data integration identifies three dysregulated genes and enrichment of Central Carbon Metabolism pathway in Oral Cancer

et al. 2020

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show abstract

“…EGFR has been earlier implicated in progression, recurrence, and stemness of oral cancer [35,36]. EGFR is inappropriately activated in cancer mainly because of amplification and point mutations.…”

Section: Discussionmentioning

confidence: 99%

Analysis Using Random Forest and Data Integration Methods of Non-promoter Methylation and Expression Data Identifies Dysregulated Genes in Central Carbon Metabolism Pathway in Oral Cancer

Majumder

Mukhopadhyay

Ghosh

et al. 2020

Preprint

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Background: Studies of epigenomic alterations associated with diseases primarily focus on methylation profiles of promoter regions of genes, but not of other genomic regions. In our past work (Das et al. 2019) on patients suffering from gingivo-buccal oral cancer – the most prevalent form of cancer among males in India – we have also focused on promoter methylation changes and resultant impact on transcription profiles. Here, we have investigated alterations in non-promoter (gene-body) methylation profiles and have carried out an integrative analysis of gene-body methylation and transcriptomic data of oral cancer patients. Methods: Tumor and adjacent normal tissue samples were collected from 40 patients. Data on methylation in the non-promoter (gene-body) regions of genes and transcriptome profiles were generated and analyzed. Because of high dimensionality and highly correlated nature of these data, we have used Random Forest (RF) and other data-analytical methods.Results: Our integrative analysis of non-promoter methylation and transcriptome data has revealed significant methylation-driven alterations in some genes that also significantly impact on their transcription levels. These changes result in enrichment of the Central Carbon Metabolism (CCM) pathway, primarily by dysregulation (overexpression) of (a) NTRK3, which plays a dual role as an oncogene and a tumor suppressor; (b) SLC7A5 (LAT1) which is a transporter dedicated to essential amino acids, and is overexpressed in cancer cells to meet the increased demand for nutrients that include glucose and essential amino acids; and, (c) EGFR which has been earlier implicated in progression, recurrence, and stemness of oral cancer, but we provide evidence of epigenetic impact on overexpression of this gene for the first time. Conclusions: In rapidly dividing cancer cells, metabolic reprogramming from normal cells takes place to enable enhanced proliferation. In the present analysis, we have identified that among oral cancer patients, genes in the CCM pathway – that plays a fundamental role in metabolic reprogramming – are significantly dysregulated because of perturbation of methylation in non-promoter regions of the genome. This result compliments our previous result that perturbation of promoter methylation results in significant changes in key genes that regulate the feedback process of DNA methylation for the maintenance of normal cell division.

show abstract

“…EGFR has been earlier implicated in progression, recurrence, and stemness of oral cancer [43,44]. EGFR is inappropriately activated in cancer mainly because of amplification and point mutations.…”

Section: Discussionmentioning

confidence: 99%

Analysis Using Random Forest and Data Integration Methods of Non-promoter Methylation and Expression Data Identifies Dysregulated Genes in Central Carbon Metabolism Pathway in Oral Cancer

Mukhopadhyay

Ghosh

Das

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Studies of epigenomic alterations associated with diseases primarily focus on methylation profiles of promoter regions of genes, but not of other genomic regions. In our past work (Das et al. 2019) on patients suffering from gingivo-buccal oral cancer – the most prevalent form of cancer among males in India – we have also focused on promoter methylation changes and resultant impact on transcription profiles. Here, we have investigated alterations in non-promoter (gene-body) methylation profiles and have carried out an integrative analysis of gene-body methylation and transcriptomic data of oral cancer patients. Methods: Tumor and adjacent normal tissue samples were collected from 40 patients. Data on methylation in the non-promoter (gene-body) regions of genes and transcriptome profiles were generated and analyzed. Because of high dimensionality and highly correlated nature of these data, we have used Random Forest (RF) and other data-analytical methods.Results: Integrative analysis of non-promoter methylation and transcriptome data revealed significant methylation-driven alterations in some genes that also significantly impact on their transcription levels. These changes result in enrichment of the Central Carbon Metabolism (CCM) pathway, primarily by dysregulation (overexpression) of (a) NTRK3, which plays a dual role as an oncogene and a tumor suppressor; (b) SLC7A5 (LAT1) which is a transporter dedicated to essential amino acids, and is overexpressed in cancer cells to meet the increased demand for nutrients that include glucose and essential amino acids; and, (c) EGFR which has been earlier implicated in progression, recurrence, and stemness of oral cancer, but we provide evidence of epigenetic impact on overexpression of this gene for the first time.Conclusions: In rapidly dividing cancer cells, metabolic reprogramming from normal cells takes place to enable enhanced proliferation. Here, we have identified that among oral cancer patients, genes in the CCM pathway – that plays a fundamental role in metabolic reprogramming – are significantly dysregulated because of perturbation of methylation in non-promoter regions of the genome. This result compliments our previous result that perturbation of promoter methylation results in significant changes in key genes that regulate the feedback process of DNA methylation for the maintenance of normal cell division.

show abstract

Overexpression of EGFR in Oral Premalignant Lesions and OSCC and Its Impact on Survival and Recurrence

Cited by 9 publications

References 36 publications

Application of Random Forest and data integration identifies three dysregulated genes and enrichment of Central Carbon Metabolism pathway in Oral Cancer

Application of Random Forest and data integration identifies three dysregulated genes and enrichment of Central Carbon Metabolism pathway in Oral Cancer

Analysis Using Random Forest and Data Integration Methods of Non-promoter Methylation and Expression Data Identifies Dysregulated Genes in Central Carbon Metabolism Pathway in Oral Cancer

Analysis Using Random Forest and Data Integration Methods of Non-promoter Methylation and Expression Data Identifies Dysregulated Genes in Central Carbon Metabolism Pathway in Oral Cancer

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