HK3 is correlated with immune infiltrates and predicts response to immunotherapy in non-small cell lung cancer.

Zhan Tuo,Jun Liu,Xin Zheng,Chunyan Zou,Yan Zong,Yi Lv,Jie Li

doi:10.1002/ctm2.6

Abstract

BackgroundWith the knowledge of tumor immunobiology deepening among researchers, the breakthroughs in the field of tumor immunotherapy in recent years have provided new approaches for cancer therapy. While patients who receive treatment are all at risk of side effects, about one‐fifth of them have sustained responses. It is crucial to figure out the underlying mechanism of how the immune system regulates the nonsmall cell lung cancer (NSCLC) microenvironment to improve the benefit of immunotherapy. Regarding glucose metabolism, the initial step is to generate glucose‐6‐phosphate by phosphorylating glucose with hexokinases‐3 (HK3). According to a recent study, HK3 has a functional role in the treatment of acute promyelocytic leukemia and colorectal cancer.ResultsHere, 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 tissues may be related to immune status. By analyzing The Cancer Genome Atlas (TCGA) data, we found that the expression of HK3 was closely related to the main clinical features as well as to molecular characteristics. We also predicted that cases with low expression of HK3 were usually malignant entities and were shown to be obvious genomic aberrations of driver oncogenes. At the same time, gene ontology analysis based on significantly related genes in HK3 expression showed that HK3 expression was linked to inflammatory activity and immune response. Additionally, HK3 showed a remarkable trend in predicting the efficacy of immunotherapy for patients receiving Keytruda (PD‐1 monoclonal antibody) treatment.ConclusionsThis is the first comprehensive study to characterize HK3 expression in NSCLC from molecular and clinical aspects.

Highlights

With the knowledge of tumor immunobiology deepening among researchers, the breakthroughs in the field of tumor immunotherapy in recent years have provided new approaches for cancer therapy
Based on the data from Tumor Immune Estimation Resource (TIMER) and The Cancer Genome Atlas (TCGA), we studied the relationship between the expression of HK3 and the infiltration of nonsmall cell lung cancer (NSCLC)
A series of data, including the transcriptome expression data of 566 cases of lung adenocarcinoma (LUAD) and 484 cases of squamous cell carcinoma (LUSC), cases with mutated gene data corresponding to cases with RNA sequence data,[22] and proteomic analysis based on Reverse Phase Protein Array (RPPA) were downloaded from TCGA

Summary

Introduction

With the knowledge of tumor immunobiology deepening among researchers, the breakthroughs in the field of tumor immunotherapy in recent years have provided new approaches for cancer therapy. While patients who receive treatment are all at risk of side effects, about one-fifth of them have sustained responses. It is crucial to figure out the underlying mechanism of how the immune system regulates the nonsmall cell lung cancer (NSCLC) microenvironment to improve the benefit of immunotherapy. HK3 showed a remarkable trend in predicting the efficacy of immunotherapy for patients receiving Keytruda (PD-1 monoclonal antibody) treatment. Conclusions: This is the first comprehensive study to characterize HK3 expression in NSCLC from molecular and clinical aspects. Immune-related mechanisms have great effects on the treatment of NSCLC. Most NSCLCs are refractory to current immunotherapies This has raised our interest in finding the underlying mechanism of how the immune system regulates the microenvironment of NSCLC to improve immunotherapy benefits

Methods

Results

Conclusion