Tuo Zhan, Zheng Xin, Zong Yan, Li Jie, Zou Chunyan, Lv Yi, Liu Jun
Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
The People's Hospital of Guangxi Zhuang Autonomous Region Nanning, Guangxi, 530021, China.
Clin Transl Med. 2020 Jan;10(1):319-330. doi: 10.1002/ctm2.6.
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. 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.
Here, 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.
This is the first comprehensive study to characterize HK3 expression in NSCLC from molecular and clinical aspects.
随着研究人员对肿瘤免疫生物学认识的不断深入，近年来肿瘤免疫治疗领域的突破为癌症治疗提供了新方法。虽然接受治疗的患者都有出现副作用的风险，但其中约五分之一的患者有持续反应。弄清楚免疫系统如何调节非小细胞肺癌（NSCLC）微环境以提高免疫治疗效果的潜在机制至关重要。关于葡萄糖代谢，第一步是通过己糖激酶-3（HK3）将葡萄糖磷酸化生成6-磷酸葡萄糖。根据最近的一项研究，HK3在急性早幼粒细胞白血病和结直肠癌的治疗中具有功能性作用。
在此，我们研究了糖酵解途径基因与免疫检查点基因的共表达关系，发现HK3在肿瘤组织中的表达可能与免疫状态有关。通过分析癌症基因组图谱（TCGA）数据，我们发现HK3的表达与主要临床特征以及分子特征密切相关。我们还预测，HK3低表达的病例通常是恶性实体，并且显示出驱动癌基因明显的基因组畸变。同时，基于HK3表达中显著相关基因的基因本体分析表明，HK3表达与炎症活性和免疫反应有关。此外，HK3在预测接受可瑞达（PD-1单克隆抗体）治疗的患者免疫治疗疗效方面呈现出显著趋势。
这是第一项从分子和临床方面对NSCLC中HK3表达进行全面表征的研究。
