Characterization of Glycolysis-Associated Molecules in the Tumor Microenvironment Revealed by Pan-Cancer Tissues and Lung Cancer Single Cell Data

Abstract

<jats:p>Altered metabolism is a hallmark of cancer and glycolysis is one of the important factors promoting tumor development. There is however still a lack of molecular characterization glycolysis and comprehensive studies related to tumor glycolysis in the pan-cancer landscape. Here, we applied a gene expression signature to quantify glycolysis in 9229 tumors across 25 cancer types and 7875 human lung cancer single cells and verified the robustness of signature using defined glycolysis samples from previous studies. We classified tumors and cells into glycolysis score-high and -low groups, demonstrated their prognostic associations, and identified genome and transcriptome molecular features associated with glycolysis activity. We observed that glycolysis score-high tumors were associated with worse prognosis across cancer types. High glycolysis tumors exhibited specific driver genes altered by copy number aberrations (CNAs) in most cancer types. Tricarboxylic acid (TCA) cycle, DNA replication, tumor proliferation and other cancer hallmarks were more active in glycolysis-high tumors. Glycolysis signature was strongly correlated with hypoxia signature in all 25 cancer tissues (r &gt; 0.7) and cancer single cells (r &gt; 0.8). In addition, HSPA8 and P4HA1 were screened out as the potential modulating factors to glycolysis as their expression were highly correlated with glycolysis score and glycolysis genes, which enables future efforts for therapeutic options to block the glycolysis and control tumor progression. Our study provides a comprehensive molecular-level understanding of glycolysis with a large sample data and demonstrates the hypoxia pressure, growth signals, oncogene mutation and other potential signals could activate glycolysis, thereby to regulate cell cycle, energy material synthesis, cell proliferation and cancer progression.</jats:p>

Candida Administration in Bilateral Nephrectomy Mice Elevates Serum (1→3)-β-D-glucan That Enhances Systemic Inflammation Through Energy Augmentation in Macrophages

“…Among these ATP productions associated genes, most genes are coded for enzymes in glycolysis pathway except for PINK -1 that is represented for a mitochondrial enzyme [ 47 ]. Notably, direction of the gene expression in LPS-activated macrophages was similar to WGP+LPS stimulated cells except for the increase in glycolysis enzymes [ 48 ]; LDHA , PGK1 , and ENO2 , after WGP+LPS activation ( Figure 6 H). These data implied an impact of WGP on enhanced ATP production, perhaps mainly through the acceleration of the glycolysis pathway.…”

Immune and Metabolic Dysregulated Coding and Non-coding RNAs Reveal Survival Association in Uterine Corpus Endometrial Carcinoma

“…To further investigate the roles of these UCEC-related genes, GSEA was performed using clusterProfiler ( Yu et al, 2012 ; Figures 3C–F ). The glycolytic pathway, whose high level in tumors, including UCEC, exhibits specific driver genes in most cancer types ( Wei et al, 2020 ), was enriched by upregulated genes in UCEC ( Figure 3D ). Upregulated genes in UCEC were also enriched in a hypoxia-related pathway ( Ruan et al, 2009 ; Figure 3E ).…”

The investigation of the volatile metabolites of lung cancer from the microenvironment of malignant pleural effusion

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