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

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.

Mutation p.Arg127Pro in the 1A Domain of KRT16 Causes Pachyonychia Congenita in Chinese Patient: A Case Report of PC Associated with Acral Melanoma

“… 13 Relative paper clarified that six hub genes, including FABP5, IVL, KRT6A, KRT15, KRT16, and TIMP2, were significant value in predicting transformation from nevi to melanoma. 14 , 15 In addition, in this case report, we found that the mutation of KRT16 in PC correlated with the occurrence and transformation of melanoma. To clarify whether KRT16 mutation is closely related to the conversion of PC to MM is the key point of our next work.…”

Multimodal analyses of vitiligo skin identifies tissue characteristics of stable disease

“…Whether these drugs will also inhibit keratinocyte-derived signals that affect immune cell and melanocyte recruitment is unclear and represents an unexplored area for drug targeting in vitiligo. Interestingly, stress keratinocytes expressing KRT6 , KRT16 , and S100A8/9 have been identified in the human epidermis of psoriasis and melanomas, raising the possibility that they can play a wide variety of roles in the diseased skin TME ( 57 – 59 ). Further studies on stress keratinocytes will improve our understanding of how keratinocyte states affect the TME and contribute to disease pathogenesis.…”

133 Multimodal analyses of vitiligo skin identifies tissue characteristics of stable disease

“…Interestingly, stress keratinocytes expressing KRT6, 16 and S100A8/9 have been identified in the human epidermis of psoriasis and melanomas, raising the possibility that they can play a wide variety of roles in the diseased skin tissue microenvironment (57)(58)(59). Further studies on stress keratinocytes will improve our understanding how keratinocyte states affect the tissue microenvironment and contribute to disease pathogenesis.…”