Identification and validation of a novel HOX-related classifier signature for predicting prognosis and immune microenvironment in pediatric gliomas
Background: Pediatric gliomas (PGs) are highly aggressive and predominantly occur in young children. In pediatric gliomas, abnormal expression of Homeobox (HOX) family genes (HFGs) has been observed and is associated with the development and progression of the disease. Studies have found that overex...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-07-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2023.1203650/full |
| _version_ | 1797775047355531264 |
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| author | Jiao Zhang Xueguang Zhang Junyan Su Jiali Zhang Siyao Liu Li Han Mengyuan Liu Dawei Sun |
| author_facet | Jiao Zhang Xueguang Zhang Junyan Su Jiali Zhang Siyao Liu Li Han Mengyuan Liu Dawei Sun |
| author_sort | Jiao Zhang |
| collection | DOAJ |
| description | Background: Pediatric gliomas (PGs) are highly aggressive and predominantly occur in young children. In pediatric gliomas, abnormal expression of Homeobox (HOX) family genes (HFGs) has been observed and is associated with the development and progression of the disease. Studies have found that overexpression or underexpression of certain HOX genes is linked to the occurrence and prognosis of gliomas. This aberrant expression may contribute to the dysregulation of important pathological processes such as cell proliferation, differentiation, and metastasis. This study aimed to propose a novel HOX-related signature to predict patients’ prognosis and immune infiltrate characteristics in PGs.Methods: The data of PGs obtained from publicly available databases were utilized to reveal the relationship among abnormal expression of HOX family genes (HFGs), prognosis, tumor immune infiltration, clinical features, and genomic features in PGs. The HFGs were utilized to identify heterogeneous subtypes using consensus clustering. Then random forest-supervised classification algorithm and nearest shrunken centroid algorithm were performed to develop a prognostic signature in the training set. Finally, the signature was validated in an internal testing set and an external independent cohort.Results: Firstly, we identified HFGs significantly differentially expressed in PGs compared to normal tissues. The individuals with PGs were then divided into two heterogeneous subtypes (HOX-SI and HOX-SII) based on HFGs expression profiles. HOX-SII showed higher total mutation counts, lower immune infiltration, and worse prognosis than HOX-SI. Then, we constructed a HOX-related gene signature (including HOXA6, HOXC4, HOXC5, HOXC6, and HOXA-AS3) based on the cluster for subtype prediction utilizing random forest supervised classification and nearest shrunken centroid algorithm. The signature was revealed to be an independent prognostic factor for patients with PGs by multivariable Cox regression analysis.Conclusion: Our study provides a novel method for the prognosis classification of PGs. The findings also suggest that the HOX-related signature is a new biomarker for the diagnosis and prognosis of patients with PGs, allowing for more accurate survival prediction. |
| first_indexed | 2024-03-12T22:29:10Z |
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| id | doaj.art-ea2ed452145b41a6967a746a93b6328d |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-03-12T22:29:10Z |
| publishDate | 2023-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-ea2ed452145b41a6967a746a93b6328d2023-07-21T18:25:42ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2023-07-011110.3389/fcell.2023.12036501203650Identification and validation of a novel HOX-related classifier signature for predicting prognosis and immune microenvironment in pediatric gliomasJiao Zhang0Xueguang Zhang1Junyan Su2Jiali Zhang3Siyao Liu4Li Han5Mengyuan Liu6Dawei Sun7Department of Cardiology, Capital Medical University Electric Power Teaching Hospital, State Grid Beijing Electric Power Hospital, Beijing, ChinaDepartment of Nephrology, Capital Medical University Electric Power Teaching Hospital, State Grid Beijing Electric Power Hospital, Beijing, ChinaBeijing ChosenMed Clinical Laboratory Co Ltd., Beijing, ChinaBeijing ChosenMed Clinical Laboratory Co Ltd., Beijing, ChinaBeijing ChosenMed Clinical Laboratory Co Ltd., Beijing, ChinaBeijing ChosenMed Clinical Laboratory Co Ltd., Beijing, ChinaBeijing ChosenMed Clinical Laboratory Co Ltd., Beijing, ChinaBeijing ChosenMed Clinical Laboratory Co Ltd., Beijing, ChinaBackground: Pediatric gliomas (PGs) are highly aggressive and predominantly occur in young children. In pediatric gliomas, abnormal expression of Homeobox (HOX) family genes (HFGs) has been observed and is associated with the development and progression of the disease. Studies have found that overexpression or underexpression of certain HOX genes is linked to the occurrence and prognosis of gliomas. This aberrant expression may contribute to the dysregulation of important pathological processes such as cell proliferation, differentiation, and metastasis. This study aimed to propose a novel HOX-related signature to predict patients’ prognosis and immune infiltrate characteristics in PGs.Methods: The data of PGs obtained from publicly available databases were utilized to reveal the relationship among abnormal expression of HOX family genes (HFGs), prognosis, tumor immune infiltration, clinical features, and genomic features in PGs. The HFGs were utilized to identify heterogeneous subtypes using consensus clustering. Then random forest-supervised classification algorithm and nearest shrunken centroid algorithm were performed to develop a prognostic signature in the training set. Finally, the signature was validated in an internal testing set and an external independent cohort.Results: Firstly, we identified HFGs significantly differentially expressed in PGs compared to normal tissues. The individuals with PGs were then divided into two heterogeneous subtypes (HOX-SI and HOX-SII) based on HFGs expression profiles. HOX-SII showed higher total mutation counts, lower immune infiltration, and worse prognosis than HOX-SI. Then, we constructed a HOX-related gene signature (including HOXA6, HOXC4, HOXC5, HOXC6, and HOXA-AS3) based on the cluster for subtype prediction utilizing random forest supervised classification and nearest shrunken centroid algorithm. The signature was revealed to be an independent prognostic factor for patients with PGs by multivariable Cox regression analysis.Conclusion: Our study provides a novel method for the prognosis classification of PGs. The findings also suggest that the HOX-related signature is a new biomarker for the diagnosis and prognosis of patients with PGs, allowing for more accurate survival prediction.https://www.frontiersin.org/articles/10.3389/fcell.2023.1203650/fullHOX family genesprognosisimmune infiltratessignaturepediatric gliomas |
| spellingShingle | Jiao Zhang Xueguang Zhang Junyan Su Jiali Zhang Siyao Liu Li Han Mengyuan Liu Dawei Sun Identification and validation of a novel HOX-related classifier signature for predicting prognosis and immune microenvironment in pediatric gliomas Frontiers in Cell and Developmental Biology HOX family genes prognosis immune infiltrates signature pediatric gliomas |
| title | Identification and validation of a novel HOX-related classifier signature for predicting prognosis and immune microenvironment in pediatric gliomas |
| title_full | Identification and validation of a novel HOX-related classifier signature for predicting prognosis and immune microenvironment in pediatric gliomas |
| title_fullStr | Identification and validation of a novel HOX-related classifier signature for predicting prognosis and immune microenvironment in pediatric gliomas |
| title_full_unstemmed | Identification and validation of a novel HOX-related classifier signature for predicting prognosis and immune microenvironment in pediatric gliomas |
| title_short | Identification and validation of a novel HOX-related classifier signature for predicting prognosis and immune microenvironment in pediatric gliomas |
| title_sort | identification and validation of a novel hox related classifier signature for predicting prognosis and immune microenvironment in pediatric gliomas |
| topic | HOX family genes prognosis immune infiltrates signature pediatric gliomas |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2023.1203650/full |
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