Genetic Signatures: CD44 Single-Nucleotide Polymorphisms Affect Cell Surface Expression and Elevate Risk in Head and Neck Squamous Cell Carcinoma
PURPOSEThis study aimed to investigate the impact of single-nucleotide polymorphisms (SNPs) in the CD44 gene, specifically in the 3'UTR region (rs13347) and intronic region (rs187115), on the cell surface expression of CD44 protein and the risk of development of head and neck squamous cell carc...
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| Format: | Article |
| Language: | English |
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American Society of Clinical Oncology
2024-11-01
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| Series: | JCO Global Oncology |
| Online Access: | https://ascopubs.org/doi/10.1200/GO.24.00084 |
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| author | Muhammad Kashif Shah Jahan Sadia Minhas Ali Amar Romeeza Tahir Haseeb Nisar Faheem Shehzad Abdul Hanan Nagi Nadeem Afzal |
| author_facet | Muhammad Kashif Shah Jahan Sadia Minhas Ali Amar Romeeza Tahir Haseeb Nisar Faheem Shehzad Abdul Hanan Nagi Nadeem Afzal |
| author_sort | Muhammad Kashif |
| collection | DOAJ |
| description | PURPOSEThis study aimed to investigate the impact of single-nucleotide polymorphisms (SNPs) in the CD44 gene, specifically in the 3'UTR region (rs13347) and intronic region (rs187115), on the cell surface expression of CD44 protein and the risk of development of head and neck squamous cell carcinoma (HNSCC).MATERIALS AND METHODSThe study involved analysis of 85 samples and 85 healthy controls. Immunohistochemistry (IHC) and flow cytometry were used to assess cell surface protein expression using CD44 antibody. DNA from formalin-fixed paraffin-embedded tissue sections was isolated and amplified using targeted primers. Sanger sequencing of the resultant amplified products was performed to determine the genotypes of the CD44 rs13347 and rs187115 SNPs. GTEx and RegulomeDB were queried to evaluate the genotypic effects of these variants on target gene expression and regulation.RESULTSA comparison between patients with HNSCC and healthy controls revealed a significant association between CD44 rs13347 and an increased risk of HNSCC in all the analyzed models, especially the TT genotype showed a significantly higher risk with an odds ratio of 8.69 (95% CI, 2.35 to 32.09; P = .0003). However, no significant association was found between CD44 rs187115 and HNSCC in any of the models analyzed (all P > .05). Other notable findings included significant associations between CD44 rs13347 genotype and age (P = .031), number of CD44-positive tumor cells (P = .049), CD44 staining intensity (SI; P = .039), and CD44 immunoreactivity score (IRS) status (P = .019).CONCLUSIONThe T allele and homozygous TT genotype of CD44 rs13347 SNP were associated with increased susceptibility to HNSCC and decreased proportion of CD44-positive tumor cells, low SI, and reduced IRS. |
| format | Article |
| id | doaj-art-06fb58fca4f742ba985ea44481ca097b |
| institution | Kabale University |
| issn | 2687-8941 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | American Society of Clinical Oncology |
| record_format | Article |
| series | JCO Global Oncology |
| spelling | doaj-art-06fb58fca4f742ba985ea44481ca097b2025-01-30T20:59:05ZengAmerican Society of Clinical OncologyJCO Global Oncology2687-89412024-11-011010.1200/GO.24.00084Genetic Signatures: CD44 Single-Nucleotide Polymorphisms Affect Cell Surface Expression and Elevate Risk in Head and Neck Squamous Cell CarcinomaMuhammad Kashif0Shah Jahan1Sadia Minhas2Ali Amar3Romeeza Tahir4Haseeb Nisar5Faheem Shehzad6Abdul Hanan Nagi7Nadeem Afzal8Department of Oral Pathology, University of Health Sciences, Lahore, PakistanInstitute of Allied Health Sciences, University of Health Sciences, Lahore, PakistanDepartment of Oral Pathology, Akhtar Saeed Medical and Dental College, Lahore, PakistanInstitute of Allied Health Sciences, University of Health Sciences, Lahore, PakistanDepartment of Immunology, University of Health Sciences, Lahore, PakistanDepartment of Life-Sciences, University of Management and Technology, Lahore, PakistanInstitute of Allied Health Sciences, University of Health Sciences, Lahore, PakistanChughtai Lahore Laboratory, Lahore, PakistanDepartment of Pathology, Akhtar Saeed Medical and Dental College, Lahore, PakistanPURPOSEThis study aimed to investigate the impact of single-nucleotide polymorphisms (SNPs) in the CD44 gene, specifically in the 3'UTR region (rs13347) and intronic region (rs187115), on the cell surface expression of CD44 protein and the risk of development of head and neck squamous cell carcinoma (HNSCC).MATERIALS AND METHODSThe study involved analysis of 85 samples and 85 healthy controls. Immunohistochemistry (IHC) and flow cytometry were used to assess cell surface protein expression using CD44 antibody. DNA from formalin-fixed paraffin-embedded tissue sections was isolated and amplified using targeted primers. Sanger sequencing of the resultant amplified products was performed to determine the genotypes of the CD44 rs13347 and rs187115 SNPs. GTEx and RegulomeDB were queried to evaluate the genotypic effects of these variants on target gene expression and regulation.RESULTSA comparison between patients with HNSCC and healthy controls revealed a significant association between CD44 rs13347 and an increased risk of HNSCC in all the analyzed models, especially the TT genotype showed a significantly higher risk with an odds ratio of 8.69 (95% CI, 2.35 to 32.09; P = .0003). However, no significant association was found between CD44 rs187115 and HNSCC in any of the models analyzed (all P > .05). Other notable findings included significant associations between CD44 rs13347 genotype and age (P = .031), number of CD44-positive tumor cells (P = .049), CD44 staining intensity (SI; P = .039), and CD44 immunoreactivity score (IRS) status (P = .019).CONCLUSIONThe T allele and homozygous TT genotype of CD44 rs13347 SNP were associated with increased susceptibility to HNSCC and decreased proportion of CD44-positive tumor cells, low SI, and reduced IRS.https://ascopubs.org/doi/10.1200/GO.24.00084 |
| spellingShingle | Muhammad Kashif Shah Jahan Sadia Minhas Ali Amar Romeeza Tahir Haseeb Nisar Faheem Shehzad Abdul Hanan Nagi Nadeem Afzal Genetic Signatures: CD44 Single-Nucleotide Polymorphisms Affect Cell Surface Expression and Elevate Risk in Head and Neck Squamous Cell Carcinoma JCO Global Oncology |
| title | Genetic Signatures: CD44 Single-Nucleotide Polymorphisms Affect Cell Surface Expression and Elevate Risk in Head and Neck Squamous Cell Carcinoma |
| title_full | Genetic Signatures: CD44 Single-Nucleotide Polymorphisms Affect Cell Surface Expression and Elevate Risk in Head and Neck Squamous Cell Carcinoma |
| title_fullStr | Genetic Signatures: CD44 Single-Nucleotide Polymorphisms Affect Cell Surface Expression and Elevate Risk in Head and Neck Squamous Cell Carcinoma |
| title_full_unstemmed | Genetic Signatures: CD44 Single-Nucleotide Polymorphisms Affect Cell Surface Expression and Elevate Risk in Head and Neck Squamous Cell Carcinoma |
| title_short | Genetic Signatures: CD44 Single-Nucleotide Polymorphisms Affect Cell Surface Expression and Elevate Risk in Head and Neck Squamous Cell Carcinoma |
| title_sort | genetic signatures cd44 single nucleotide polymorphisms affect cell surface expression and elevate risk in head and neck squamous cell carcinoma |
| url | https://ascopubs.org/doi/10.1200/GO.24.00084 |
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