Identification, Validation, and Functional Annotations of Genome-Wide Profile Variation between Melanocytic Nevus and Malignant Melanoma

Author:

Han Wei12ORCID,Xu Wen-Hao34,Wang Jian-Xiong12,Hou Jia-Min12,Zhang Hai-Liang34ORCID,Zhao Xiao-Yu12ORCID,Shen Guo-Liang12ORCID

Affiliation:

1. Department of Burn and Plastic Surgery, The First Affiliated Hospital of Soochow University, Suzhou 215000, China

2. Department of Surgery, Soochow University, Suzhou 215000, China

3. Department of Urology, Fudan University Shanghai Cancer Center, Shanghai 200032, China

4. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China

Abstract

Cutaneous melanoma (CM) is known as an aggressive malignant cancer; some of which are directly derived from melanocytic nevi, which have been attracting growing attention from the last decades. This study focused on comprehensive identification, validation, and functional annotations of prognostic differentially expressed genes (DEGs) between melanocytic nevus and malignant melanoma in genome-wide profiles. DEGs were obtained using three chip datasets from GEO database to identify after standardization annotation. A total of 73 DEGs were identified as possible candidate prognostic biomarkers between melanocytic nevus and malignant melanoma. In addition, survival curves indicated that six hub genes, including FABP5, IVL, KRT6A, KRT15, KRT16, and TIMP2, were significant prognostic signatures for CM and of significant value to predict transformation from nevi to melanoma. Furthermore, immunohistochemistry staining was performed to validate differential expression levels and prognostic implications of six hub genes between CM tissue and nevus tissues from the First Affiliated Hospital of Soochow University cohort. It suggested that significantly elevated FABP5, IVL, KRT6A, KRT15, KRT16, and TIMP2 proteins expressed in the CM than in the nevus tissues. Functional enrichment and significant pathways of the six significant hub genes indicated that the mostly involved hallmarks include the P53 pathway, K-ras signaling, estrogen response late, and estrogen response early. In summary, this study identified significant DEGs participating in the process of malignant transformation from nevus to melanoma tissues based on comprehensive genomic profiles. Transcription profiles of FABP5, IVL, KRT6A, KRT15, KRT16, and TIMP2 provided clues of prognostic implications, which might help us evaluate malignant potential of nevus and underlying carcinogenesis progress from melanocytic nevus to melanoma.

Publisher

Hindawi Limited

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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