Research Paper Volume 14, Issue 7 pp 3233—3258

The role of fructose 1,6-bisphosphate-mediated glycolysis/gluconeogenesis genes in cancer prognosis

Chien-Hsiu Li1, , Ming-Hsien Chan1, , Yu-Chan Chang2, ,

  • 1 Genomics Research Center, Academia Sinica, Taipei, Taiwan
  • 2 Department of Biomedical Imaging and Radiological Sciences, National Yang Ming Chiao Tung University, Taipei, Taiwan

Received: November 22, 2021       Accepted: March 25, 2022       Published: April 11, 2022
How to Cite

Copyright: © 2022 Li et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Metabolic reprogramming and elevated glycolysis levels are associated with tumor progression. However, despite cancer cells selectively inhibiting or expressing certain metabolic enzymes, it is unclear whether differences in gene profiles influence patient outcomes. Therefore, identifying the differences in enzyme action may facilitate discovery of gene ontology variations to characterize tumors. Fructose-1,6-bisphosphate (F-1,6-BP) is an important intermediate in glucose metabolism, particularly in cancer. Gluconeogenesis and glycolysis require fructose-1,6-bisphosphonates 1 (FBP1) and fructose-bisphosphate aldolase A (ALDOA), which participate in F-1,6-BP conversion. Increased expression of ALDOA and decreased expression of FBP1 are associated with the progression of various forms of cancer in humans. However, the exact molecular mechanism by which ALDOA and FBP1 are involved in the switching of F-1,6-BP is not yet known. As a result of their pancancer pattern, the relationship between ALDOA and FBP1 in patient prognosis is reversed, particularly in lung adenocarcinoma (LUAD) and liver hepatocellular carcinoma (LIHC). Using The Cancer Genome Atlas (TCGA), we observed that FBP1 expression was low in patients with LUAD and LIHC tumors, which was distinct from ALDOA. A similar trend was observed in the analysis of Cancer Cell Line Encyclopedia (CCLE) datasets. By dissecting downstream networks and possible upstream regulators, using ALDOA and FBP1 as the core, we identified common signatures and interaction events regulated by ALDOA and FBP1. Notably, the identified effectors dominated by ALDOA or FBP1 were distributed in opposite patterns and can be considered independent prognostic indicators for patients with LUAD and LIHC. Therefore, uncovering the effectors between ALDOA and FBP1 will lead to novel therapeutic strategies for cancer patients.


F-1,6-BP: Fructose-1, 6-bisphosphate; ALDOA: Fructose-bisphosphate aldolase A; ALDOB: Fructose-bisphosphate aldolase B; ALDOC: Fructose-bisphosphate aldolase C; LUAD: lung adenocarcinoma; LIHC: liver hepatocellular carcinoma; TCGA: The Cancer Genome Atlas; CCLE: Cancer Cell Line Encyclopedia; HCC: hepatocellular carcinoma; G3P: glyceraldehyde 3-phosphate; DHAP: dihydroxyacetone phosphate; PanCancer Atlas dataset and Firehose Legacy dataset: TCGA database; IPA: Ingenuity Pathway Analysis; FBP1: Fructose-1,6- bisphosphonates 1; FBP2: Fructose-1,6- bisphosphonates 2; HR: Hazard ratio; N or n: Sample size; Affy: Affymetrix; RNAseq: RNA sequencing.