Based on different immune responses under the glucose metabolizing type of papillary thyroid cancer and the response to anti-PD-1 therapy

Abstract

Glucose metabolism-related genes play an important role in the development and immunotherapy of many tumours, but their role in thyroid cancer is ambiguous. To investigate the role of glucose metabolism-related genes in the development of papillary thyroid cancer (PTC) and their correlation with the clinical outcome of PTC, we collected transcriptomic data from 501 PTC patients in the Cancer Genome Atlas (TCGA). We performed nonnegative matrix decomposition clustering of 2752 glucose metabolism-related genes from transcriptome data and classified PTC patients into three subgroups (C1 for high activation of glucose metabolism, C2 for low activation of glucose metabolism and C3 for moderate activation of glucose metabolism) based on the activation of different glucose metabolism-related genes in 10 glucose metabolism-related pathways. We found a positive correlation between the activation level of glucose metabolism and the tumour mutation burden (TMB), neoantigen number, mRNA stemness index (mRNAsi), age, and tumour stage in PTC patients. Next, we constructed a prognostic prediction model for PTC using six glucose metabolism-related genes (PGBD5, TPO, IGFBPL1, TMEM171, SOD3, TDRD9) and constructed a nomogram based on the risk score and clinical parameters of PTC patients. Both the prognostic risk prediction model and nomogram had high stability and accuracy for predicting the progression-free interval (PFI) in PTC patients. Patients were then divided into high-risk and low-risk groups by risk score. The high-risk group was sensitive to paclitaxel and anti-PD-1 treatment, and the low-risk group was sensitive to sorafenib treatment. We found that the high-risk group was enriched in inflammatory response pathways and associated with high level of immune cell infiltration. To verify the accuracy of the prognostic prediction model, we knocked down PGBD5 in PTC cells and found that the proliferation ability of PTC cells was significantly reduced. This suggests that PGBD5 may be a relatively important oncogene in PTC. Our study constructed a prognostic prediction model and classification of PTC by glucose metabolism-related genes, which provides a new perspective on the role of glucose metabolism in the development and immune microenvironment of PTC and in guiding chemotherapy, targeted therapy and immune checkpoint blockade therapy of PTC.

Knowledge mapping of immunotherapy for thyroid cancer from 1980 to 2022: A review

“…[70] In recent years, immunotherapy has been extensively used in cancer treatment including TC. [26,[71][72][73][74][75][76][77][78][79][80][81] In this study, papers on immunotherapy for TC were studied by using bibliometric method.…”

Harnessing Immunity to Treat Advanced Thyroid Cancer

“…Despite the release of T cells from negative immune checkpoints activating antitumor T cells, only a limited number of patients respond to tumor-nonspecific immunotherapy. Patients with enriched inflammatory response pathways and high levels of immune cell infiltration may respond to ICIs in TC [ 167 ]; however, particular biomarkers to identify ICI responders are yet to be identified. PD-L1 expression in the stroma or the detection of tumor-reactive T cells using a TAA-derived epitope would be useful for determining responders to ICIs.…”

Metabolism in Cancer Stem Cells: Targets for Clinical Treatment

“…Glucose metabolism is the first and most widely studied metabolic abnormality in cancer cells ( Figure 1 ) [ 21 , 22 , 23 , 24 ]. Normal cells metabolize glucose into carbon dioxide and water through oxygen-consuming mitochondrial metabolism in physiological conditions, but convert glucose into lactic acid (glycolysis) in a low oxygen and anaerobic environment [ 25 ].…”