Deregulation of extracellular matrix modeling with molecular prognostic markers revealed by transcriptome sequencing and validations in Oral Tongue squamous cell carcinoma

Abstract Oral Tongue Squamous Cell Carcinoma (OTSCC), a distinct sub-group of head and neck cancers, is characteristically aggressive in nature with a higher incidence of recurrence and metastasis. Recent advances in therapeutics have not improved patient survival. The phenomenon of occult node meta...

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Autores principales: Soundara Viveka Thangaraj, Vidyarani Shyamsundar, Arvind Krishnamurthy, Vijayalakshmi Ramshankar
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Publicado: Nature Portfolio 2021
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spelling oai:doaj.org-article:2c5d9b55a56a48d2bd6dfa25407442e82021-12-02T11:46:06ZDeregulation of extracellular matrix modeling with molecular prognostic markers revealed by transcriptome sequencing and validations in Oral Tongue squamous cell carcinoma10.1038/s41598-020-78624-42045-2322https://doaj.org/article/2c5d9b55a56a48d2bd6dfa25407442e82021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-78624-4https://doaj.org/toc/2045-2322Abstract Oral Tongue Squamous Cell Carcinoma (OTSCC), a distinct sub-group of head and neck cancers, is characteristically aggressive in nature with a higher incidence of recurrence and metastasis. Recent advances in therapeutics have not improved patient survival. The phenomenon of occult node metastasis, even among the purportedly good prognosis group of early-stage and node-negative tongue tumors, leads to a high incidence of locoregional failure in OTSCC which needs to be addressed. In the current study, transcriptome analysis of OTSCC patients identified the key genes and deregulated pathways. A panel of 26 marker genes was shortlisted and validated using real-time PCR in a prospective cohort of 100 patients. The gene expression was correlated with clinicopathological features including occult node metastasis, survival, and therapeutic outcome. The up-regulation of a panel of 6 genes namely, matrix metalloproteinase 9 (MMP9), Laminin subunit Gamma 2 (LAMC2), Desmoglein 2 (DSG2), Plasminogen Activator Urokinase (PLAU), Forkhead Box M1 (FOXM1), and Myosin 1B (MYO1B) was associated with failure of treatment in the early stage (T1, T2). Up-regulation of Tenacin C (TNC) and Podoplanin (PDPN) was significantly correlated with occult node positivity. Immunohistochemical analysis of LAMC2, MMP9, and E-Cadherin (ECAD) confirmed these markers to be indicators of poor prognosis. We propose this panel of valuable prognostic markers can be clinically useful to identify poor prognosis and occult node metastasis in OTSCC patients.Soundara Viveka ThangarajVidyarani ShyamsundarArvind KrishnamurthyVijayalakshmi RamshankarNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Soundara Viveka Thangaraj
Vidyarani Shyamsundar
Arvind Krishnamurthy
Vijayalakshmi Ramshankar
Deregulation of extracellular matrix modeling with molecular prognostic markers revealed by transcriptome sequencing and validations in Oral Tongue squamous cell carcinoma
description Abstract Oral Tongue Squamous Cell Carcinoma (OTSCC), a distinct sub-group of head and neck cancers, is characteristically aggressive in nature with a higher incidence of recurrence and metastasis. Recent advances in therapeutics have not improved patient survival. The phenomenon of occult node metastasis, even among the purportedly good prognosis group of early-stage and node-negative tongue tumors, leads to a high incidence of locoregional failure in OTSCC which needs to be addressed. In the current study, transcriptome analysis of OTSCC patients identified the key genes and deregulated pathways. A panel of 26 marker genes was shortlisted and validated using real-time PCR in a prospective cohort of 100 patients. The gene expression was correlated with clinicopathological features including occult node metastasis, survival, and therapeutic outcome. The up-regulation of a panel of 6 genes namely, matrix metalloproteinase 9 (MMP9), Laminin subunit Gamma 2 (LAMC2), Desmoglein 2 (DSG2), Plasminogen Activator Urokinase (PLAU), Forkhead Box M1 (FOXM1), and Myosin 1B (MYO1B) was associated with failure of treatment in the early stage (T1, T2). Up-regulation of Tenacin C (TNC) and Podoplanin (PDPN) was significantly correlated with occult node positivity. Immunohistochemical analysis of LAMC2, MMP9, and E-Cadherin (ECAD) confirmed these markers to be indicators of poor prognosis. We propose this panel of valuable prognostic markers can be clinically useful to identify poor prognosis and occult node metastasis in OTSCC patients.
format article
author Soundara Viveka Thangaraj
Vidyarani Shyamsundar
Arvind Krishnamurthy
Vijayalakshmi Ramshankar
author_facet Soundara Viveka Thangaraj
Vidyarani Shyamsundar
Arvind Krishnamurthy
Vijayalakshmi Ramshankar
author_sort Soundara Viveka Thangaraj
title Deregulation of extracellular matrix modeling with molecular prognostic markers revealed by transcriptome sequencing and validations in Oral Tongue squamous cell carcinoma
title_short Deregulation of extracellular matrix modeling with molecular prognostic markers revealed by transcriptome sequencing and validations in Oral Tongue squamous cell carcinoma
title_full Deregulation of extracellular matrix modeling with molecular prognostic markers revealed by transcriptome sequencing and validations in Oral Tongue squamous cell carcinoma
title_fullStr Deregulation of extracellular matrix modeling with molecular prognostic markers revealed by transcriptome sequencing and validations in Oral Tongue squamous cell carcinoma
title_full_unstemmed Deregulation of extracellular matrix modeling with molecular prognostic markers revealed by transcriptome sequencing and validations in Oral Tongue squamous cell carcinoma
title_sort deregulation of extracellular matrix modeling with molecular prognostic markers revealed by transcriptome sequencing and validations in oral tongue squamous cell carcinoma
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/2c5d9b55a56a48d2bd6dfa25407442e8
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