Gene–Environment Interaction: Small Deletions (DELs) and Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) and Potential Implications for Therapy
Arsenic (As) is a risk factor for non-melanoma skin cancer (NMSC). From a six-year follow-up study on 7000 adults exposed to As, we reported the associations of single-nucleotide variation in tumor tissue and gene expression. Here, we identify the associations of small deletions (DELs) and transcrip...
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2025-01-01
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| author | Farzana Jasmine Armando Almazan Yuliia Khamkevych Maria Argos Mohammad Shahriar Tariqul Islam Christopher R. Shea Habibul Ahsan Muhammad G. Kibriya |
| author_facet | Farzana Jasmine Armando Almazan Yuliia Khamkevych Maria Argos Mohammad Shahriar Tariqul Islam Christopher R. Shea Habibul Ahsan Muhammad G. Kibriya |
| author_sort | Farzana Jasmine |
| collection | DOAJ |
| description | Arsenic (As) is a risk factor for non-melanoma skin cancer (NMSC). From a six-year follow-up study on 7000 adults exposed to As, we reported the associations of single-nucleotide variation in tumor tissue and gene expression. Here, we identify the associations of small deletions (DELs) and transcriptomic profiles in NMSC. Comparing the (a) NMSC tissue (<i>n</i> = 32) and corresponding blood samples from each patient, and (b) an independent set of non-lesional, healthy skin (<i>n</i> = 16) and paired blood, we identified NMSC-associated DELs. Differential expressions of certain gene pathways (<i>TGF-β</i> signaling pathway, <i>IL-17</i> pathway, <i>PD-L1</i> pathway, etc.) showed significant interactions with these somatic DELs and As exposure. In low-As-exposure cases, the DELs in <i>APC</i> were associated with the up-regulation of inflamed T-Cell-associated genes by a fold change (FC) of 8.9 (95% CI 4.5–17.6), compared to 5.7 (95% CI 2.9–10.8) without <i>APC</i> DELs; in high-As-exposure cases, the <i>APC</i> DELs were associated with an FC of 5.8 (95% CI 3.5–9.8) compared to 1.2 (95% CI −1.3 to 1.8) without <i>APC</i> DELs. We report, for the first time, the significant associations of somatic DELs (many in STR regions) in NMSC tissue and As exposure with many dysregulated gene pathways. These findings may help in selecting groups of patients for potential targeted therapy like PD-L1 inhibitors, IL-17 inhibitors, and TGF-β inhibitors in the future. |
| format | Article |
| id | doaj-art-f1aeb9945da345b282ce90c665f7db4c |
| institution | Kabale University |
| issn | 2073-4409 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
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| series | Cells |
| spelling | doaj-art-f1aeb9945da345b282ce90c665f7db4c2025-01-24T13:26:39ZengMDPI AGCells2073-44092025-01-011429510.3390/cells14020095Gene–Environment Interaction: Small Deletions (DELs) and Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) and Potential Implications for TherapyFarzana Jasmine0Armando Almazan1Yuliia Khamkevych2Maria Argos3Mohammad Shahriar4Tariqul Islam5Christopher R. Shea6Habibul Ahsan7Muhammad G. Kibriya8Institute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USAInstitute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USAInstitute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USADepartment of Environmental Health, School of Public Health, Boston University, Boston, MA 02118, USAInstitute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USAUChicago Research Bangladesh (URB), University of Chicago, Dhaka 1230, BangladeshDivision of Dermatology, Department of Medicine, University of Chicago, Chicago, IL 60637, USAInstitute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USAInstitute for Population and Precision Health (IPPH), University of Chicago, Chicago, IL 60637, USAArsenic (As) is a risk factor for non-melanoma skin cancer (NMSC). From a six-year follow-up study on 7000 adults exposed to As, we reported the associations of single-nucleotide variation in tumor tissue and gene expression. Here, we identify the associations of small deletions (DELs) and transcriptomic profiles in NMSC. Comparing the (a) NMSC tissue (<i>n</i> = 32) and corresponding blood samples from each patient, and (b) an independent set of non-lesional, healthy skin (<i>n</i> = 16) and paired blood, we identified NMSC-associated DELs. Differential expressions of certain gene pathways (<i>TGF-β</i> signaling pathway, <i>IL-17</i> pathway, <i>PD-L1</i> pathway, etc.) showed significant interactions with these somatic DELs and As exposure. In low-As-exposure cases, the DELs in <i>APC</i> were associated with the up-regulation of inflamed T-Cell-associated genes by a fold change (FC) of 8.9 (95% CI 4.5–17.6), compared to 5.7 (95% CI 2.9–10.8) without <i>APC</i> DELs; in high-As-exposure cases, the <i>APC</i> DELs were associated with an FC of 5.8 (95% CI 3.5–9.8) compared to 1.2 (95% CI −1.3 to 1.8) without <i>APC</i> DELs. We report, for the first time, the significant associations of somatic DELs (many in STR regions) in NMSC tissue and As exposure with many dysregulated gene pathways. These findings may help in selecting groups of patients for potential targeted therapy like PD-L1 inhibitors, IL-17 inhibitors, and TGF-β inhibitors in the future.https://www.mdpi.com/2073-4409/14/2/95non-melanoma skin cancerbasal-cell carcinomasomatic mutationsmall deletionshort tandem repeatarsenic |
| spellingShingle | Farzana Jasmine Armando Almazan Yuliia Khamkevych Maria Argos Mohammad Shahriar Tariqul Islam Christopher R. Shea Habibul Ahsan Muhammad G. Kibriya Gene–Environment Interaction: Small Deletions (DELs) and Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) and Potential Implications for Therapy Cells non-melanoma skin cancer basal-cell carcinoma somatic mutation small deletion short tandem repeat arsenic |
| title | Gene–Environment Interaction: Small Deletions (DELs) and Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) and Potential Implications for Therapy |
| title_full | Gene–Environment Interaction: Small Deletions (DELs) and Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) and Potential Implications for Therapy |
| title_fullStr | Gene–Environment Interaction: Small Deletions (DELs) and Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) and Potential Implications for Therapy |
| title_full_unstemmed | Gene–Environment Interaction: Small Deletions (DELs) and Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) and Potential Implications for Therapy |
| title_short | Gene–Environment Interaction: Small Deletions (DELs) and Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) and Potential Implications for Therapy |
| title_sort | gene environment interaction small deletions dels and transcriptomic profiles in non melanoma skin cancer nmsc and potential implications for therapy |
| topic | non-melanoma skin cancer basal-cell carcinoma somatic mutation small deletion short tandem repeat arsenic |
| url | https://www.mdpi.com/2073-4409/14/2/95 |
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