Transcriptional profiling identifies an interferon‐associated host immune response in invasive squamous cell carcinoma of the skin

Abstract

Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent the 2 most common types of nonmelanoma skin cancer. Both derive from keratinocytes but show a distinct biological behavior. Here we present transcriptional profiling data of a large cohort of tumor patients (SCC, n 5 42; BCC, n 5 114). Differentially expressed genes reflect known features of SCC and BCC including the typical cytokeratin pattern as well as upregulation of characteristic cell proliferation genes. Additionally, we found increased expression of interferon (IFN)-regulated genes (including IFI27, IFI30, Mx1, IRF1 and CXCL9) in SCC, and to a lower extent in BCC. The expression of IFN-regulated genes correlated with the extent of the lesional immune-cell infiltrate. Immunohistological examinations confirmed the expression of IFN-regulated genes in association with a CXCR31 cytotoxic inflammatory infiltrate on the protein level. Of note, a small subset of SCC samples with low expression of IFN-regulated genes included most organ transplant recipients receiving immunosuppressive medication. Collectively, our findings support the concept that IFN-associated host responses play an important role in tumor immunosurveillance in the skin.

A novel in silico reverse-transcriptomics-based identification and blood-based validation of a panel of sub-type specific biomarkers in lung cancer

“…This finding is supported by the findings that it is downregulated in gastric [47] and recurrent breast cancers [48]. However, IRF1 may not always act as a tumor-suppressor, as there is a report that it is upregulated in skin squamous cell carcinoma [49]. Therefore, our observation of upregulated IRF1 in NSCLC samples requires further attention to explore the precise role of this TF in various cancers.…”

Gene expression changes in tumor free tongue tissue adjacent to tongue squamous cell carcinoma

“…IFI27 is suggested to be involved in proliferation of skin keratinocytes [29] and up-regulated in breast cancer, SCC of the skin and ovarian cancer [30–32]. In ovarian cancer IFI27 is associated with patient survival where high IFI27 expression correlates with poor disease free survival [30].…”

Osteosarcoma is characterised by reduced expression of markers of osteoclastogenesis and antigen presentation compared with normal bone

“…Interestingly, we observed a significant increase in the expression of five genes with overlapping functions in antigen presentation and osteoclastogenesis in the good responder group – IFI30 ( P =0.0005), TYROBP/DAP12 ( P =0.002), TMSB10 ( P =0.003), CTSB ( P =0.004), and SPP1 ( P =0.037). The IFI30 expression, in melanoma (Goldstein et al , 2008) and squamous cell carcinoma (Wenzel et al , 2008), has been shown to enhance antigen presentation and to activate CTSB (Goldstein et al , 2008), which is required for osteoclast fusion during differentiation (McMichael et al , 2009). In addition, TYROBP/DAP12 is associated with active innate immune responses (Lanier, 2009) and, together with SPP1, also has a crucial function in osteoclast differentiation (Humphrey et al , 2004; Mocsai et al , 2004; Dalla-Torre et al , 2006; Inui et al , 2009).…”