TP53-Associated Ion Channel Genes Serve as Prognostic Predictor and Therapeutic Targets in Head and Neck Squamous Cell Carcinoma

TP53 mutations are the most occurred mutation in HNSCC which might affect the ion channel genes. We aim to investigate the ion channel gene alteration under TP53 mutation and their prognostic implication. The overall mutation status of HNSCC were explored. By screening the TP53-associated ion channe...

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Main Authors: Jing Sun PhD, Xijiao Yu PhD, Lande Xue MD, Shu Li PhD, Jianxia Li CD, Dongdong Tong MD, Yi Du PhD
Format: Article
Language:English
Published: SAGE Publishing 2020-11-01
Series:Technology in Cancer Research & Treatment
Online Access:https://doi.org/10.1177/1533033820972344
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spelling doaj-f8b31bfce1254854b7b9e6ebf2657d5d2020-12-02T22:34:12ZengSAGE PublishingTechnology in Cancer Research & Treatment1533-03382020-11-011910.1177/1533033820972344TP53-Associated Ion Channel Genes Serve as Prognostic Predictor and Therapeutic Targets in Head and Neck Squamous Cell CarcinomaJing Sun PhD0Xijiao Yu PhD1Lande Xue MD2Shu Li PhD3Jianxia Li CD4Dongdong Tong MD5Yi Du PhD6 Jing Sun and Xijiao Yu contributed equally to this work. Jing Sun and Xijiao Yu contributed equally to this work. Department of Periodontology, Jinan Stomatological Hospital, Jinan, Shandong, China Hospital of Stomatology, , Jinan, Shandong, China Department of Periodontology, Jinan Stomatological Hospital, Jinan, Shandong, China Department of Oral and Maxillofacial, School and Hospital of Stomatology, , Jinan, Shandong, China Department of Endodontics, Jinan Stomatological Hospital, Jinan, Shandong, ChinaTP53 mutations are the most occurred mutation in HNSCC which might affect the ion channel genes. We aim to investigate the ion channel gene alteration under TP53 mutation and their prognostic implication. The overall mutation status of HNSCC were explored. By screening the TP53-associated ion channel genes (TICGs), an ion channel prognostic signature (ICPS) was established through a series of machine learning algorithms. The ICPS was then evaluated and its clinical significance was explored. 82 TICGs differentially expressed between TP53WT and TP53MUT were screened. Using univariate regression analysis and LASSO regression analysis and multivariate regression analysis, an ICPS containing 7 ion channel genes was established. A series of evaluation was carried out which proved the predictive ability of ICPS. Functional analysis of ICPS revealed that cancer-related pathways were enriched in high-risk group. Next, for clinical application, a nomogram was constructed based on ICPS and other independent clinicopathological factors. TP53 mutation status strongly affects the expression of ion channel genes. The ICPM we have identified is a strong indicator for HNSCC prognosis and could help with patient stratification as well as identification of novel drug targets.https://doi.org/10.1177/1533033820972344
collection DOAJ
language English
format Article
sources DOAJ
author Jing Sun PhD
Xijiao Yu PhD
Lande Xue MD
Shu Li PhD
Jianxia Li CD
Dongdong Tong MD
Yi Du PhD
spellingShingle Jing Sun PhD
Xijiao Yu PhD
Lande Xue MD
Shu Li PhD
Jianxia Li CD
Dongdong Tong MD
Yi Du PhD
TP53-Associated Ion Channel Genes Serve as Prognostic Predictor and Therapeutic Targets in Head and Neck Squamous Cell Carcinoma
Technology in Cancer Research & Treatment
author_facet Jing Sun PhD
Xijiao Yu PhD
Lande Xue MD
Shu Li PhD
Jianxia Li CD
Dongdong Tong MD
Yi Du PhD
author_sort Jing Sun PhD
title TP53-Associated Ion Channel Genes Serve as Prognostic Predictor and Therapeutic Targets in Head and Neck Squamous Cell Carcinoma
title_short TP53-Associated Ion Channel Genes Serve as Prognostic Predictor and Therapeutic Targets in Head and Neck Squamous Cell Carcinoma
title_full TP53-Associated Ion Channel Genes Serve as Prognostic Predictor and Therapeutic Targets in Head and Neck Squamous Cell Carcinoma
title_fullStr TP53-Associated Ion Channel Genes Serve as Prognostic Predictor and Therapeutic Targets in Head and Neck Squamous Cell Carcinoma
title_full_unstemmed TP53-Associated Ion Channel Genes Serve as Prognostic Predictor and Therapeutic Targets in Head and Neck Squamous Cell Carcinoma
title_sort tp53-associated ion channel genes serve as prognostic predictor and therapeutic targets in head and neck squamous cell carcinoma
publisher SAGE Publishing
series Technology in Cancer Research & Treatment
issn 1533-0338
publishDate 2020-11-01
description TP53 mutations are the most occurred mutation in HNSCC which might affect the ion channel genes. We aim to investigate the ion channel gene alteration under TP53 mutation and their prognostic implication. The overall mutation status of HNSCC were explored. By screening the TP53-associated ion channel genes (TICGs), an ion channel prognostic signature (ICPS) was established through a series of machine learning algorithms. The ICPS was then evaluated and its clinical significance was explored. 82 TICGs differentially expressed between TP53WT and TP53MUT were screened. Using univariate regression analysis and LASSO regression analysis and multivariate regression analysis, an ICPS containing 7 ion channel genes was established. A series of evaluation was carried out which proved the predictive ability of ICPS. Functional analysis of ICPS revealed that cancer-related pathways were enriched in high-risk group. Next, for clinical application, a nomogram was constructed based on ICPS and other independent clinicopathological factors. TP53 mutation status strongly affects the expression of ion channel genes. The ICPM we have identified is a strong indicator for HNSCC prognosis and could help with patient stratification as well as identification of novel drug targets.
url https://doi.org/10.1177/1533033820972344
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