Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan 10;14(2):95.
doi: 10.3390/cells14020095.

Gene-Environment Interaction: Small Deletions (DELs) and Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) and Potential Implications for Therapy

Farzana Jasmine  1 , Armando Almazan  1 , Yuliia Khamkevych  1 , Maria Argos  2 , Mohammad Shahriar  1 , Tariqul Islam  3 , Christopher R Shea  4 , Habibul Ahsan  1   5 , Muhammad G Kibriya  1   5
Affiliations

Gene-Environment Interaction: Small Deletions (DELs) and Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) and Potential Implications for Therapy

Farzana Jasmine et al. Cells. .

Abstract

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 (n = 32) and corresponding blood samples from each patient, and (b) an independent set of non-lesional, healthy skin (n = 16) and paired blood, we identified NMSC-associated DELs. Differential expressions of certain gene pathways (TGF-β signaling pathway, IL-17 pathway, PD-L1 pathway, etc.) showed significant interactions with these somatic DELs and As exposure. In low-As-exposure cases, the DELs in APC 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 APC DELs; in high-As-exposure cases, the APC 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 APC 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.

Trial registration: ClinicalTrials.gov NCT00392561.

Keywords: IL-17 signaling; TGF-β signaling; arsenic; basal-cell carcinoma; gene–environment interaction; immune checkpoint inhibitors; non-melanoma skin cancer; short tandem repeat; small deletion; somatic mutation.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Venn diagram showing overlap between the DELs identified in healthy skin tissue (in light green) and NMSC tissue (in light pink). Overlap by unique genomic coordinates are on the left Venn diagram (A), and overlap by unique gene symbols are on the right Venn diagram (B).
Figure 2
Figure 2
Top 40 genes with DELs found in (A) NMSC only, (B) common between NMSC and healthy skin, and (C) healthy skin only. Genes are shown in rows, while each column represents an individual patient.
Figure 3
Figure 3
Top 40 genes harboring the BCC-associated DELs (A) and SCC-associated DELs (B) that are not found in healthy skin tissue. Genes are shown in rows, while each column represents an individual patient.
Figure 4
Figure 4
Differential gene expression of the PD-L1 and PD-1 checkpoint pathway in BCC tissue (in blue) compared to healthy skin tissue (in red). BCC tissues with no APC DELs are shown on the left (A), and BCC tissues with APC DELs are shown on the right (B). Genes are arranged on the x-axis by expression level, and the log2-transformed gene count per million (CPM) is shown on the y-axis. Gene symbols for all the genes could not be shown on the x-axis.
Figure 5
Figure 5
Differential gene expression of TGF-β pathway in BCC tissue (in blue) compared to non-lesional skin tissue (in red). BCC tissues with no APC DELs are shown on the left (A), and BCC tissues with APC DELs are shown on the right (B). Genes are arranged on the x-axis by expression level, and the log2-transformed gene count per million (CPM) is shown on the y-axis. Gene symbols for all the genes could not be shown on the x-axis.
Figure 6
Figure 6
Differential expression of inflamed T-cell genes in BCC tissue (in blue) compared to healthy skin tissue (in red). In the upper panel, BCC tissues with no APC DELs are shown on the left (A) and BCC tissues with APC DELs are shown on the right (B). In the lower panel, BCC tissues from patients with high As exposure are shown on the left (C), and BCC tissues from patients with low As exposure are shown on the right (D). Genes are arranged on the x-axis by expression level, and the log2-transformed gene count per million (CPM) is shown on the y-axis. Gene symbols for all the genes could not be shown on the x-axis.
Figure 6
Figure 6
Differential expression of inflamed T-cell genes in BCC tissue (in blue) compared to healthy skin tissue (in red). In the upper panel, BCC tissues with no APC DELs are shown on the left (A) and BCC tissues with APC DELs are shown on the right (B). In the lower panel, BCC tissues from patients with high As exposure are shown on the left (C), and BCC tissues from patients with low As exposure are shown on the right (D). Genes are arranged on the x-axis by expression level, and the log2-transformed gene count per million (CPM) is shown on the y-axis. Gene symbols for all the genes could not be shown on the x-axis.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Jasmine F., Argos M., Khamkevych Y., Islam T., Rakibuz-Zaman M., Shahriar M., Shea C.R., Ahsan H., Kibriya M.G. Molecular Profiling and the Interaction of Somatic Mutations with Transcriptomic Profiles in Non-Melanoma Skin Cancer (NMSC) in a Population Exposed to Arsenic. Cells. 2024;13:1056. doi: 10.3390/cells13121056. - DOI - PMC - PubMed
    1. Fitzmaurice C., Abate D., Abbasi N., Abbastabar H., Abd-Allah F., Abdel-Rahman O., Abdelalim A., Abdoli A., Abdollahpour I., Abdulle A.S.M., et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2019;5:1749–1768. doi: 10.1001/jamaoncol.2019.2996. - DOI - PMC - PubMed
    1. Oh C.C., Jin A., Koh W.P. Trends of cutaneous basal cell carcinoma, squamous cell carcinoma, and melanoma among the Chinese, Malays, and Indians in Singapore from 1968–2016. JAAD Int. 2021;4:39–45. doi: 10.1016/j.jdin.2021.05.006. - DOI - PMC - PubMed
    1. Ogata D., Namikawa K., Nakano E., Fujimori M., Uchitomi Y., Higashi T., Yamazaki N., Kawai A. Epidemiology of skin cancer based on Japan’s National Cancer Registry 2016–2017. Cancer Sci. 2023;114:2986–2992. doi: 10.1111/cas.15823. - DOI - PMC - PubMed
    1. Kibriya M.G., Jasmine F., Munoz A., Islam T., Ahmed A., Tong L., Rakibuz-Zaman M., Shahriar M., Kamal M., Shea C.R., et al. Interaction of Arsenic Exposure and Transcriptomic Profile in Basal Cell Carcinoma. Cancers. 2022;14:5598. doi: 10.3390/cancers14225598. - DOI - PMC - PubMed

Publication types

Associated data