Aberrant expression and high-frequency mutations of SHARPIN in nonmelanoma skin cancer

Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) have exhibited a marked increase in incidence in previous decades and are the most common malignancies in Caucasian populations. Src homology 3 and multiple ankyrin repeat domains protein-associated RH domain-interacting protein (SHARPIN) has been identified as a commonly overexpressed proto-oncogene in several types of visceral cancer. However, to the best of our knowledge, the functions of SHARPIN in nonmelanoma skin cancer (NMSC) have not been described. The present study aimed to investigate the expression of SHARPIN protein and SHARPIN mutations in NMSC. A total of 85 BCC, 77 SCC and 21 keratoacanthoma (KA) formalin-fixed paraffin-embedded (FFPE) samples were collected. SHARPIN expression was detected using immunohistochemistry. DNA was extracted from the FFPE samples, and the sequences of SHARPIN were analyzed using polymerase chain reaction. In addition, high and moderate expression levels of SHARPIN were observed in normal skin tissues and KA samples. However, the expression of SHARPIN was absent in cancer nests and was significantly low in precancerous NMSC lesions. The total mutation frequency of SHARPIN was 21.8% in BCC and 17.0% in SCC. These data indicate that SHARPIN may serve a tumor-suppressing role and be a promising diagnostic, prognostic and therapeutic biomarker in NMSC.