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The Landscape of Transmembrane Protein Family Members in Head and Neck Cancers: Their Biological Role and Diagnostic Utility

SIMPLE SUMMARY: Transmembrane proteins (TMEM) are a large group of integral membrane proteins whose molecular and biological functions are not fully understood. It is known that some of them are involved in tumor formation and metastasis. Here, we performed a panel of TCGA data analyses to investiga...

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Autores principales: Koteluk, Oliwia, Bielicka, Antonina, Lemańska, Żaneta, Jóźwiak, Kacper, Klawiter, Weronika, Mackiewicz, Andrzej, Kazimierczak, Urszula, Kolenda, Tomasz
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507526/
https://www.ncbi.nlm.nih.gov/pubmed/34638224
http://dx.doi.org/10.3390/cancers13194737
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author Koteluk, Oliwia
Bielicka, Antonina
Lemańska, Żaneta
Jóźwiak, Kacper
Klawiter, Weronika
Mackiewicz, Andrzej
Kazimierczak, Urszula
Kolenda, Tomasz
author_facet Koteluk, Oliwia
Bielicka, Antonina
Lemańska, Żaneta
Jóźwiak, Kacper
Klawiter, Weronika
Mackiewicz, Andrzej
Kazimierczak, Urszula
Kolenda, Tomasz
author_sort Koteluk, Oliwia
collection PubMed
description SIMPLE SUMMARY: Transmembrane proteins (TMEM) are a large group of integral membrane proteins whose molecular and biological functions are not fully understood. It is known that some of them are involved in tumor formation and metastasis. Here, we performed a panel of TCGA data analyses to investigate the role of different TMEM genes in head and neck squamous cell carcinoma (HNSCC) and define their potential as biomarkers. Based on changes in the expression levels in HNSCC tumors, we selected four TMEM genes: ANO1, TMEM156, TMEM173, and TMEM213 and associated them with patient survival. We also demonstrated that the expression of those TMEMs highly correlates with the enrichment of genes involved in numerous biological processes, especially metastasis formation and immune response. Thus, we propose ANO1, TMEM156, TMEM173, and TMEM213 as new biomarkers and potential targets for personalized therapy of HNSCC. ABSTRACT: Background: Transmembrane proteins (TMEM) constitute a large family of proteins spanning the entirety of the lipid bilayer. However, there is still a lack of knowledge about their function or mechanism of action. In this study, we analyzed the expression of selected TMEM genes in patients with head and neck squamous cell carcinoma (HNSCC) to learn their role in tumor formation and metastasis. Materials and Methods: Using TCGA data, we analyzed the expression levels of different TMEMs in both normal and tumor samples and compared those two groups depending on clinical-pathological parameters. We selected four TMEMs whose expression was highly correlated with patient survival status and subjected them to further analysis. The pathway analysis using REACTOME and the gene set enrichment analysis (GSEA) were performed to evaluate the association of those TMEMs with genes involved in hallmarks of cancer as well as in oncogenic and immune-related pathways. In addition, the fractions of different immune cell subpopulations depending on TMEM expression were estimated in analyzed patients. The results for selected TMEMs were validated using GEO data. All analyses were performed using the R package, Statistica, and Graphpad Prism. Results: We demonstrated that 73% of the analyzed TMEMs were dysregulated in HNSCC and depended on tumor localization, smoking, alcohol consumption, or HPV infection. The expression levels of ANO1, TMEM156, TMEM173, and TMEM213 correlated with patient survival. The four TMEMs were also upregulated in HPV-positive patients. The elevated expression of those TMEMs correlated with the enrichment of genes involved in cancer-related processes, including immune response. Specifically, overexpression of TMEM156 and TMEM173 was associated with immune cell mobilization and better survival rates, while the elevated ANO1 expression was linked with metastasis formation and worse survival. Conclusions: In this work, we performed a panel of in silico analyses to discover the role of TMEMs in head and neck squamous cell carcinoma. We found that ANO1, TMEM156, TMEM173, and TMEM213 correlated with clinical status and immune responses in HNSCC patients, pointing them as biomarkers for a better prognosis and treatment. This is the first study describing such the role of TMEMs in HNSCC. Future clinical trials should confirm the potential of those genes as targets for personalized therapy of HNSCC.
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spelling pubmed-85075262021-10-13 The Landscape of Transmembrane Protein Family Members in Head and Neck Cancers: Their Biological Role and Diagnostic Utility Koteluk, Oliwia Bielicka, Antonina Lemańska, Żaneta Jóźwiak, Kacper Klawiter, Weronika Mackiewicz, Andrzej Kazimierczak, Urszula Kolenda, Tomasz Cancers (Basel) Article SIMPLE SUMMARY: Transmembrane proteins (TMEM) are a large group of integral membrane proteins whose molecular and biological functions are not fully understood. It is known that some of them are involved in tumor formation and metastasis. Here, we performed a panel of TCGA data analyses to investigate the role of different TMEM genes in head and neck squamous cell carcinoma (HNSCC) and define their potential as biomarkers. Based on changes in the expression levels in HNSCC tumors, we selected four TMEM genes: ANO1, TMEM156, TMEM173, and TMEM213 and associated them with patient survival. We also demonstrated that the expression of those TMEMs highly correlates with the enrichment of genes involved in numerous biological processes, especially metastasis formation and immune response. Thus, we propose ANO1, TMEM156, TMEM173, and TMEM213 as new biomarkers and potential targets for personalized therapy of HNSCC. ABSTRACT: Background: Transmembrane proteins (TMEM) constitute a large family of proteins spanning the entirety of the lipid bilayer. However, there is still a lack of knowledge about their function or mechanism of action. In this study, we analyzed the expression of selected TMEM genes in patients with head and neck squamous cell carcinoma (HNSCC) to learn their role in tumor formation and metastasis. Materials and Methods: Using TCGA data, we analyzed the expression levels of different TMEMs in both normal and tumor samples and compared those two groups depending on clinical-pathological parameters. We selected four TMEMs whose expression was highly correlated with patient survival status and subjected them to further analysis. The pathway analysis using REACTOME and the gene set enrichment analysis (GSEA) were performed to evaluate the association of those TMEMs with genes involved in hallmarks of cancer as well as in oncogenic and immune-related pathways. In addition, the fractions of different immune cell subpopulations depending on TMEM expression were estimated in analyzed patients. The results for selected TMEMs were validated using GEO data. All analyses were performed using the R package, Statistica, and Graphpad Prism. Results: We demonstrated that 73% of the analyzed TMEMs were dysregulated in HNSCC and depended on tumor localization, smoking, alcohol consumption, or HPV infection. The expression levels of ANO1, TMEM156, TMEM173, and TMEM213 correlated with patient survival. The four TMEMs were also upregulated in HPV-positive patients. The elevated expression of those TMEMs correlated with the enrichment of genes involved in cancer-related processes, including immune response. Specifically, overexpression of TMEM156 and TMEM173 was associated with immune cell mobilization and better survival rates, while the elevated ANO1 expression was linked with metastasis formation and worse survival. Conclusions: In this work, we performed a panel of in silico analyses to discover the role of TMEMs in head and neck squamous cell carcinoma. We found that ANO1, TMEM156, TMEM173, and TMEM213 correlated with clinical status and immune responses in HNSCC patients, pointing them as biomarkers for a better prognosis and treatment. This is the first study describing such the role of TMEMs in HNSCC. Future clinical trials should confirm the potential of those genes as targets for personalized therapy of HNSCC. MDPI 2021-09-22 /pmc/articles/PMC8507526/ /pubmed/34638224 http://dx.doi.org/10.3390/cancers13194737 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Koteluk, Oliwia
Bielicka, Antonina
Lemańska, Żaneta
Jóźwiak, Kacper
Klawiter, Weronika
Mackiewicz, Andrzej
Kazimierczak, Urszula
Kolenda, Tomasz
The Landscape of Transmembrane Protein Family Members in Head and Neck Cancers: Their Biological Role and Diagnostic Utility
title The Landscape of Transmembrane Protein Family Members in Head and Neck Cancers: Their Biological Role and Diagnostic Utility
title_full The Landscape of Transmembrane Protein Family Members in Head and Neck Cancers: Their Biological Role and Diagnostic Utility
title_fullStr The Landscape of Transmembrane Protein Family Members in Head and Neck Cancers: Their Biological Role and Diagnostic Utility
title_full_unstemmed The Landscape of Transmembrane Protein Family Members in Head and Neck Cancers: Their Biological Role and Diagnostic Utility
title_short The Landscape of Transmembrane Protein Family Members in Head and Neck Cancers: Their Biological Role and Diagnostic Utility
title_sort landscape of transmembrane protein family members in head and neck cancers: their biological role and diagnostic utility
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8507526/
https://www.ncbi.nlm.nih.gov/pubmed/34638224
http://dx.doi.org/10.3390/cancers13194737
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