Merkel cell carcinoma (MCC) is a rare but highly malignant skin cancer. Immune checkpoint blockade therapy was showing successful results in MCC treatment. However, its immunokinetics are not completely clear. We collected 90 specimens from 71 patients and 53 blood serum samples from 21 patients with MCC from 9 facilities. mRNA was extracted from formalin fixed paraffin embedded (FFPE) tissues. Next generation sequencing revealed that MCC samples could be divided into two types. “immune active type” showed better clinical outcomes than “cell division type”. Glucose-6-Phosphate Dehydrogenase (G6PD) was one of the most significantly up-regulated gene in “cell division type”. G6PD expression correlated with the presence or absence of lymph node or distant metastases during the course and negatively correlated with high or low of PD-L1 expression with the top significance in 395 genes both. Immunohistochemical staining of G6PD was also correlated with disease specific survival and showed less heterogeneity compared with PD-L1 expression. G6PD activity was measurable by the blood serum test and detection values significantly increased as the cancer stage progression and significantly decreased after treatment. G6PD supplies reductive energy to cells by maintaining NADPH levels. This NADPH maintains the concentration of glutathione, a major intracellular antioxidant, and protects the tumor cell from oxidative damage. G6PD is not only an immunohistochemically and serum-detectable prognostic marker, but also an indicator to classify cases based on the tumor immune activity and a potential biomarker for immune checkpoint blockade therapy.

ESDR262 - Glucose-6-Phosphate Dehydrogenase is a Promising Biomarker for Prognosis and Immune Activity Prediction in Merkel Cell Carcinoma

50th Annual Meeting of the European Society for Dermatological Research. VIRTUAL MEETING