Single-stranded DNA binding protein 2 (SSBP2) is a tumor suppressor candidate. In this study, the expression level and clinicopathological significance of SSBP2 in squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) were evaluated. We also identified biological pathways associated with a set of genes potentially related to SSBP2. Immunohistochemistry (IHC) was performed on 70 SCC and 146 BCC cases to assess SSBP2 expression semi-quantitatively. In addition, the associations between SSBP2 expression and clinicopathological characteristics were analyzed. Gene ontology (GO) enrichment analysis was performed using publicly available data and web-based bioinformatics tools. Compared with BCC, SCC had a significantly low SSBP2 expression (p < 0.001). In total, 12 (17.1%) of the 70 SCC cases and 30 (20.5%) of the 146 BCC cases showed low SSBP2 expression. Among SCC cases, ulceration (p = 0.005) and a deep level of invasion (p = 0.012) showed an association with low SSBP2 expression. Local recurrence was slightly more common in the SCC subgroup with low SSBP2 expression, although the difference was not significant (p = 0.058). Using GO enrichment analysis, we identified several biological functions performed by a set of 36 genes in SCC. SSBP2 evaluation using IHC can be helpful in the differential diagnosis of SCC and BCC. SSBP2 expression was associated with tumor invasiveness in SCC.
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