HK3 Is Correlated with Immune Infiltrates and Predicts Response to Immunotherapy in NSCLC

Abstract

Along with increasing understanding of tumor immune biology, recent breakthroughs in cancer immunotherapies have shed a new light on cancer therapy. However, only about 20% of treated patients have durable responses, while all are at risk for side effects.It is crucial to figure out the underly regulation mechanism of the immune microenvironment of NSCLC to improve the benefit of immuotherapy. Hexokinases-3(HK3) phosphorylate glucose to produce glucose-6-phosphate, the first step in most glucose metabolism pathways. Recent study reported functional role of HK3 in acute promyelocytic leukemia and colorectal cancer. In this present study, we studied the co-expression relationship between the glycolytic pathway gene and the immune checkpoint gene, and found that the expression of HK3 in tumor tissue may be related to immune status. By analyzing the TCGA data we found that HK3 expression was highly correlated with major clinical and molecular characteristics. Cases with low HK3 expression were more likely to be predicted as malignant entities and frequent with genomic aberrations of driver oncogenes. Moreover, gene ontology analysis based on significantly correlated genes of HK3 expression exhibited that HK3 was associated with immune responses and inflammatory activities. In addition, HK3 shows a significant trend in predicting the efficacy of immunotherapy for patients accept Keytruda (PD-1 monoclonal antibody) treatment. This study is the first integrative study characterizing HK3 expression of NSCLC both in molecular and clinic. Funding Statement: This work was supported by the grants from the National Natural Science Foundation of China (NO. 81472708). Declaration of Interests: The authors declare no potential conflicts of interest. Ethics Approval Statement: All protocols using human samples were reviewed and approved by the Ethical Committee of Huazhong University of Science and Technology. Written informed consent was obtained from all patients.