Ann Dermatol.  2018 Oct;30(5):536-543. 10.5021/ad.2018.30.5.536.

Gene Expression Patterns of Cutaneous Squamous Cell Carcinoma and Actinic Keratosis: Biomarkers Screening for Skin Disease Diagnosis

Affiliations
  • 1Department of Dermatology, Affiliated Hospital of Hebei University of Engineering, Handan, China. lizhiufeng369@163.com LBG66@163.com

Abstract

BACKGROUND
Actinic keratosis (AK) was an intraepidermal tumor which caused by ultraviolet irradiation-induced skin damage.
OBJECTIVE
The aim was to screen biomarkers for development of skin disease by comparing the gene expression profiles between cutaneous squamous cell carcinoma (CSCC) and AK.
METHODS
GSE45216 with 30 cutaneous squamous cell carcinoma patients and 10 actinic keratosis patients were downloaded and significance analysis of microarrays was processed to screen differently expressed genes (DEGs). Fisher's exact test was processed for DEGs enrichment. Pathway relationship network systematically reflected the signal conduction and synergism between enriched pathways based on Kyoto Encyclopedia of Genes and Genomes database. Gene co-expression network was constructed according to gene expression data. Quantitative real-time-PCR was used to verify screened biomarkers.
RESULTS
Total 410 DEGs were screened and enriched into various functions, such as signal transduction and negative regulation of apoptotic process. They also participated into cytokine-cytokine receptor interaction and focal adhesion. The pathway relationship network was constructed with 27 nodes. Hub nodes with higher degree of this network were mitogen-activated protein kinase signaling pathway and apoptosis. The gene co-expression network was constructed with 39 nodes. Thereinto, hub node was ELOVL fatty acid elongase. The expression levels of ELOVL4 and HPGD were significantly higher in CSCC samples than that in AK samples, while the expression levels of INHBA and LAMC2 in CSCC samples were significantly lower than that in AK samples.
CONCLUSION
These screened genes, including ELOVL4, HPGD, INHBA and LAMC2, played important roles in transformation from AK to CSCC.

Keyword

Actinic keratosis; Diagnosis; Genes; Neoplasms

MeSH Terms

Actins*
Apoptosis
Biomarkers*
Carcinoma, Squamous Cell*
Diagnosis*
Epithelial Cells*
Focal Adhesions
Gene Expression*
Genome
Humans
Keratosis, Actinic*
Mass Screening*
Protein Kinases
Signal Transduction
Skin Diseases*
Skin*
Transcriptome
Actins
Biomarkers
Protein Kinases

Figure

  • Fig. 1 Pathway relationship network. Red nodes represent pathways involved up-regulated differently expressed genes (DEGs) while blue nodes represent pathways involved down-regulated DEGs. Yellow nodes represent pathways involved both up- and down-regulated DEGs. Arrows represent regulatory directions. ECM: extracellular matrix, PPAR: peroxisome proliferator-activated receptor-gamma, ErbB: epidermal growth factor receptor, TGF: transforming growth factor.

  • Fig. 2 Gene co-expression network. Violet nodes are DEGs and edges are relationships among these genes. The sizes of these nodes represent degree of these nodes. The positive correlation was represented by solid lines, while the negative correlation was shown by dotted lines. DEGs: differently expressed genes.

  • Fig. 3 Quantitative RT-PCR of biomarkers. RT-PCR: real-time polymerase chain reaction, CSCC: cutaneous squamous cell carcinoma, AK: actinic keratosis. *p<0.05, **p<0.01.


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