A Novel Risk Factor Model Based on Glycolysis-Associated Genes for Predicting the Prognosis of Patients With Prostate Cancer

Abstract

BackgroundProstate cancer (PCa) is one of the most prevalent cancers among males, and its mortality rate is increasing due to biochemical recurrence (BCR). Glycolysis has been proven to play an important regulatory role in tumorigenesis. Although several key regulators or predictors involved in PCa progression have been found, the relationship between glycolysis and PCa is unclear; we aimed to develop a novel glycolysis-associated multifactor prediction model for better predicting the prognosis of PCa.MethodsDifferential mRNA expression profiles derived from the Cancer Genome Atlas (TCGA) PCa cohort were generated through the “edgeR” package. Glycolysis-related genes were obtained from the GSEA database. Univariate Cox and LASSO regression analyses were used to identify genes significantly associated with disease-free survival. ROC curves were applied to evaluate the predictive value of the model. An external dataset derived from Gene Expression Omnibus (GEO) was used to verify the predictive ability. Glucose consumption and lactic production assays were used to assess changes in metabolic capacity, and Transwell assays were used to assess the invasion and migration of PC3 cells.ResultsFive glycolysis-related genes were applied to construct a risk score prediction model. Patients with PCa derived from TCGA and GEO (GSE70770) were divided into high-risk and low-risk groups according to the median. In the TCGA cohort, the high-risk group had a poorer prognosis than the low-risk group, and the results were further verified in the GSE70770 cohort. In vitro experiments demonstrated that knocking down HMMR, KIF20A, PGM2L1, and ANKZF1 separately led to less glucose consumption, less lactic production, and inhibition of cell migration and invasion, and the results were the opposite with GPR87 knockdown.ConclusionThe risk score based on five glycolysis-related genes may serve as an accurate prognostic marker for PCa patients with BCR.

Identification of a Hypoxia-Related Gene Model for Predicting the Prognosis and Formulating the Treatment Strategies in Kidney Renal Clear Cell Carcinoma

“…Ankyrin repeat and zinc finger peptidyl tRNA hydrolase 1 (ANKZF1) is essential for the oxidative stress and the maintenance of mitochondrial integrity ( 28 ). Some bioinformatics analyses have proved that ANKZF1 based genes signature can predict the prognosis of patients with colon cancer, renal cell carcinoma, and prostate cancer ( 14 , 29 – 33 ). ETS proto-oncogene 1, transcription factor (ETS1) is a transcription factor belong to the ETS domain family.…”

HMMR Promotes Prostate Cancer Proliferation and Metastasis via AURKA/mTORC2/E2F1 Positive Feedback Loop

“…Currently, abundant studies indicate that HMMR plays multiple functional roles in regulating proliferation and metastasis 11 , maintenance of stemness 12 and chemotherapy resistance 13 in various tumours, such as lung cancer 14 , liver cancer 15 , bladder cancer 11 , gastric cancer 16 . Additionally, our previous study found that HMMR was elevated in PCa tumours tissues and associated with poor prognosis 17 . Although the oncogenicity of HMMR in PCa is preliminary disclosed, the precise roles and mechanisms remain largely poor understood, which deserves further explored.…”

“…Our previous study characterised HMMR as a crucial tumour driver in PCa 17 . Based on this, we carried out a series of experiments to explore the roles and mechanisms of HMMR.…”

Targeting mitochondrial metabolism for metastatic cancer therapy

“…Understanding the metabolic mechanisms that regulate metastasis would, therefore, provide valuable information about precision medicine strategies to prevent or treat metastases. Glycolysis does play an important role in tumorigenesis because separately knocking down several glycolysis‐regulating genes (HMMR, KIF20A, PGM2L1, and ANKZF1) resulted in less glucose consumption, less lactic acid production, and reduced cell migration and invasion of prostate cancer cells 40 . A risk score based on glycolysis‐related genes may serve as an accurate prognostic marker for prostate cancer patients with biochemical recurrence.…”

“…Glycolysis does play an important role in tumorigenesis because separately knocking down several glycolysis-regulating genes (HMMR, KIF20A, PGM2L1, and ANKZF1) resulted in less glucose consumption, less lactic acid production, and reduced cell migration and invasion of prostate cancer cells. 40 A risk score based on glycolysis-related genes may serve as an accurate prognostic marker for prostate cancer patients with biochemical recurrence. For these reasons, most research in recent years has focused on glycolytic pathways driving tumor growth (Warburg effect).…”