Glucose-6-Phosphate Dehydrogenase as a Prognostic Predictor Correlates with the Tumor Immune Activity Including Programmed Death Ligand-1 Expression in Merkel Cell Carcinoma

Here we performed RNA sequencing to evaluate immune response and comprehensively estimate prognostic values of immunogenic factors in MCC.　 Experimental Design: 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. Analyses of next generation sequencing data, immunohistochemical staining and blood serum tests were performed. Results: 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. Conclusion: G6PD expression was an immunohistochemically and serum-detectable prognostic marker and negatively correlated with immune activity including PD-L1 associate with the prediction of immunotherapy response.