Abstract
While increased glycolysis has been identified as a cancer marker and attracted much attention in thyroid cancer (THCA), the prognostic role of it remains to be further elucidated. Here we aimed to determine a specific glycolysis-associated risk model to predict THCA patients' survival. We also explored the interaction between this signature and tumor immune microenvironment and performed drug screening to identify specific drugs targeting the glycolysis-associated signature. Six genes (CHST6, POM121C, PPFIA4, STC1, TGFBI, and FBP2) comprised the specific model, which was an independent prognostic indicator in THCA patients determined by univariate, LASSO and multivariate Cox regression analyses. The receiver operating characteristic (ROC) curve analysis confirmed the excellent clinical performance of the prognostic signature. According to the specific gene signature, patients were categorized into high- and low-risk subgroups. The high-risk group was characterized by decreased immune score and elevated tumor purity, as well as worser survival prognosis compared to the low-risk group. We also validated the expression of these genes in clinical samples and in-vitro experiments. Lastly, we identified potential drugs targeting the glycolysis-associated signature. The derived glycolysis-related signature is an independent prognostic biomarker for THCA patients and might be used as an efficacy of biomarker for drug-sensitivity prediction.
Highlights
Thyroid cancer (THCA) is one of the most frequently diagnosed malignancies of the endocrine system worldwide, and this cancer incidence rate is still on the rise [1,2,3]
A univariate Cox regression was used to explore the interaction of the glycolysis-related genes with the overall survival of thyroid cancer (THCA) patients and determined 17 survival-related genes in THCA patients when the p < 0.05 (Figure 1A)
We calculated the risk score for each THCA patient according to this formula and categorized the patients into high- or low-risk groups (Figures 2A–C)
Summary
Thyroid cancer (THCA) is one of the most frequently diagnosed malignancies of the endocrine system worldwide, and this cancer incidence rate is still on the rise [1,2,3]. Known as aerobic glycolysis, is a phenomenon whereby various types of cancer cells characterize by excessive conversion of glucose to lactate for their energy substrate regardless of oxygen levels [5]. Lactate, produced by glycolytic tumor cells, plays crucial roles in the suppression of anticancer immune cells and promotes the tumor recurrence following anticancer therapies [10]. The high accumulation of lactate in tumor microenvironment (TME), which lowers extracellular pH to 6.0–6.5, blocks the function and proliferation rate of T cells [11]. High concentrations of lactate in TME affects antitumor therapy, which leads to the suggestion that inhibiting glycolytic pathway, and lactate production may provide an effective and potential strategy to enhance anticancer agents
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