Warburg Effect and Cancer Survival


  • William Panosyan Crescenta Valley High School
  • Daniel Panosyan Crescenta Valley High School
  • Eduard Panosyan Parent Advisor




Warburg effect, Cancer survival, Lactate dehydrogenase A


Warburg effect is a major metabolic shift of glycolysis in cancer cells towards anaerobic fermentation. Key reaction here overproduces lactate from pyruvate catalyzed by lactate dehydrogenase-A (LDHA). Augmented Warburg effect and oncometabolism may contribute to cancer progression worsening patients’ survival. Expressions of various key enzymes were used as surrogates to validate the clinical influence of metabolic alterations in cancers. Expression and Kaplan-Meier survival data were extracted from the R2 Genomics Analysis and Visualization Platform (R2) and Human Protein Atlas (HPA). Expression of LDHA gene was 2-4 times higher than normal tissues in certain cancers including breast, colon, genitourinary and B-cell lymphomas. No cancer specificity or strong associations were observed between RNA and protein expressions of LDHA. However, higher LDHA gene expression correlated with poorer survival in renal, liver, lung, pancreatic, cervical and breast cancers. These cancers moderately or strongly stained for LDHA protein. Per HPA, gliomas had low LDHA without survival correlation. Nevertheless, this correlation was observed in the largest glioblastoma database (R2). Furthermore, 3 of 4 medulloblastoma subtypes showed poor survival with higher LDHA. Contrarily, in B-cell lymphomas and colon cancer high LDHA was a favorable prognostic marker. Poor survival correlated with high expression of other enzymes for glycolysis and amino acid metabolism (PFK-isoenzymes, GFPT2 and BCAT1). Warburg effect may not be universally dominant for all cancers, but most cancers have high LDHA and/or associated poor survival, confirming importance of this metabolic derangement in cancers. Heterogeneity of metabolic alterations can serve to diversify anti-metabolic strategies for targeted anti-cancer therapies.


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Author Biographies

Daniel Panosyan, Crescenta Valley High School

Senior at Crescenta Valley High School

Eduard Panosyan, Parent Advisor

Eduard H. Panosyan, MD

Pediatric Hematology-Oncology

Lundquist Research Institute at Harbor-UCLA Medical Center

References or Bibliography

(http://r2.amc.nl), R. G. A. a. V. P. R2: Genomics Analysis and Visualization Platform (http://r2.amc.nl), (https://hgserver1.amc.nl/cgi-bin/r2/main.cgi), R2: Kaplan Meier Scanner (amc.nl) (https://hgserver1.amc.nl/cgi-bin/r2/main.cgi?option=kaplan_main).

Akella, N. M., Ciraku, L., & Reginato, M. J. (2019). Fueling the fire: emerging role of the hexosamine biosynthetic pathway in cancer. BMC biology, 17(1), 52-52. doi: 10.1186/s12915-019-0671-3

Ananieva, E. A., & Wilkinson, A. C. (2018). Branched-chain amino acid metabolism in cancer. Current opinion in clinical nutrition and metabolic care, 21(1), 64-70. doi: 10.1097/MCO.0000000000000430

Antibody-drug Conjugate, a Potential Trojan Horse to Fight Cancer https://www.genscript.com/antibody-news/antibody-drug-conjugate-a-potential-trojan-horse-to-fight-cancer.html. (May 18, 2021).

Atlas, T. H. P. The Human Protein Atlas (https://www.proteinatlas.org/humanproteome/pathology), (https://www.proteinatlas.org/ENSG00000134333-LDHA/pathology).

Avramis, V. I., & Panosyan, E. H. (2005). Pharmacokinetic/Pharmacodynamic Relationships of Asparaginase Formulations: The Past, the Present and Recommendations for the Future. Clinical Pharmacokinetics, 44(4), 367-393.

Broome, J. D. (1963). Evidence that the L-asparaginase of guinea pig serum is responsible for its antilymphoma effects. I. Properties of the L-asparaginase of guinea pig serum in relation to those of the antilymphoma substance. The Journal of experimental medicine, 118(1), 99-120. doi: 10.1084/jem.118.1.99

El-Galaly, T. C., Villa, D., Gormsen, L. C., Baech, J., Lo, A., & Cheah, C. Y. (2018). FDG-PET/CT in the management of lymphomas: current status and future directions. J Intern Med, 284(4), 358-376. doi: 10.1111/joim.12813

Ertel, I. J., Nesbit, M. E., Hammond, D., Weiner, J., & Sather, H. (1979). Effective Dose of l-Asparaginase for Induction of Remission in Previously Treated Children with Acute Lymphocytic Leukemia: A Report from Childrens Cancer Study Group. Cancer Research, 39(10), 3893-3896.

Feng, Y., Xiong, Y., Qiao, T., Li, X., Jia, L., & Han, Y. (2018). Lactate dehydrogenase A: A key player in carcinogenesis and potential target in cancer therapy. Cancer medicine, 7(12), 6124-6136. doi: 10.1002/cam4.1820

Hasawi, N. A., Alkandari, M. F., & Luqmani, Y. A. (2014). Phosphofructokinase: A mediator of glycolytic flux in cancer progression. Critical Reviews in Oncology/Hematology, 92(3), 312-321. doi: https://doi.org/10.1016/j.critrevonc.2014.05.007

Juraschka, K., & Taylor, M. D. (2019). Medulloblastoma in the age of molecular subgroups: a review. J Neurosurg Pediatr, 24(4), 353-363. doi: 10.3171/2019.5.peds18381

Koukourakis, M. I., & Giatromanolaki, A. (2019). Warburg effect, lactate dehydrogenase, and radio/chemo-therapy efficacy. International Journal of Radiation Biology, 95(4), 408-426. doi: 10.1080/09553002.2018.1490041

Mukherjee, S. (16 November 2010). Emperor of All Maladies: A Biography of Cancer.

Panosyan, E. H., Lin, H. J., Koster, J., & Lasky, J. L. (2017). In search of druggable targets for GBM amino acid metabolism. BMC Cancer, 17(1), 162. doi: 10.1186/s12885-017-3148-1

Potter, M., Newport, E., & Morten, K. J. (2016). The Warburg effect: 80 years on. Biochemical Society transactions, 44(5), 1499-1505. doi: 10.1042/BST20160094

Valvona, C. J., Fillmore, H. L., Nunn, P. B., & Pilkington, G. J. (2016). The Regulation and Function of Lactate Dehydrogenase A: Therapeutic Potential in Brain Tumor. Brain pathology (Zurich, Switzerland), 26(1), 3-17. doi: 10.1111/bpa.12299

Warburg, O., Wind, F., & Negelein, E. (1927). THE METABOLISM OF TUMORS IN THE BODY. The Journal of general physiology, 8(6), 519-530. doi: 10.1085/jgp.8.6.519

Wilson, M., Cummins, C. L., MacPherson, L., Sun, Y., Natarajan, K., Grundy, R. G., . . . Peet, A. C. (2013). Magnetic resonance spectroscopy metabolite profiles predict

survival in paediatric brain tumours. European journal of cancer (Oxford, England : 1990), 49(2), 457-464.



How to Cite

Panosyan, W., Panosyan, D., & Panosyan, E. (2021). Warburg Effect and Cancer Survival. Journal of Student Research, 10(4). https://doi.org/10.47611/jsrhs.v10i4.2348



HS Research Articles