Author(s):
Haya Salameh, Firas Hussein
Email(s):
ph.hayasalameh@gmail.com
DOI:
10.5958/0974-360X.2020.00240.1 
Address:
Haya Salameh1, Firas Hussein2
1Postgraduate student, Department of Biochemistry and Microbiology, Faculty of Pharmacy, Tishreen University, Lattakia, Syria.
2Assistant Professor, Department of Internal Medicine and Heamatology, Faculty of Medicine, Tishreen University, Lattakia, Syria.
*Corresponding Author
Published In:
Volume - 13,
Issue - 3,
Year - 2020
ABSTRACT:
Purpose: Cancer is defined as a group of diseases, It involve abnormal cell growth with the potential of invade and spread, it also involve with metabolic changes such as a metabolic switch from oxidative phosphorylation to increased glycolysis, even under normal oxygene conditions, this phenomenon is termed the Warburg effect[6]. Lactate dehydrogenase (LDH) is a metabolic enzyme widely expressed in almost all tissues and is detectable in serum, which catalyzes the interconversion of pyruvate and lactate during glycolysis and gluconeogenesis, and is considered to be a key checkpoint of anaerobic glycolysis. LDH levels is elevated in many types of cancer in compare to normal tissues, and it has been linked to tumor growth, maintenance, and invasion; This enzyme is receiving a great deal of attention as a potential diagnostic marker or a predictive biomarker for many types of cancer and as a therapeutic target for new therapies.[5] Lactate dehydrogenase (LDH) is regulated by the phosphatidylinositol 3-kinase/Akt/mammalian target of rapamycin (mTOR)–containing complex 1 (PI3K/Akt/TORC1) pathway as well as tumor hypoxia induced factor (HIF1). This study aimed to investigate whether lactate dehydrogenase (LDH) level in diagnostic is a marker of hypoxia, had clinical value in determining the kind of cancer or the stage of the disease in pretreatment cancer patients.[7, 9] Patients and Methods: We evaluated pretreatment serum lactate dehydrogenase (LDH) in 285 newly diagnosed cancer patients. the study samples included both men and women, It also included all kind of cancer. statistical analysis: The Shapiro- Wilk test was used to determine the distribution of continuous variables. Student’s t-test, Mann-Whitney U test, chi square, and Ficher exact test were used too.[2] Results: Baseline LDH levels 210 IU/L was an independent prognosticator for recurrence-free survival The predictive value of baseline LDH value remained significant in the subgroup analysis. LDH level <227 IU/L was identified as an independent predictor of complete remission after treatment. It helps distinguish patients with different prognosis and select patients who are more likely to benefit from normal treatment regimens. A highly significant difference was found between the survival patterns of patients with LDH levels of 233 U or less and those with LDH levels greater than 233 U. (recurrence free survival rates were 63% and 74%, respectively. Discussion: The association of LDH level with the stage of the disease in Lung cancer, Brest cancer, Germcell cancer (prostate and testicular cancer, ovarian and uterus cancer), lymphoma and leukemia was evident even after adjustment for other factors that might affect the diagnosis. Pretreatment serum LDH determinations may provide a useful means of staging in cancer types mentioned previously.[30]
Cite this article:
Haya Salameh, Firas Hussein. Diagnostic value of serum LDH in pre - Treatment Cancer Patients. Research J. Pharm. and Tech 2020; 13(3):1303-1308. doi: 10.5958/0974-360X.2020.00240.1
Cite(Electronic):
Haya Salameh, Firas Hussein. Diagnostic value of serum LDH in pre - Treatment Cancer Patients. Research J. Pharm. and Tech 2020; 13(3):1303-1308. doi: 10.5958/0974-360X.2020.00240.1 Available on: https://www.rjptonline.org/AbstractView.aspx?PID=2020-13-3-45
5. REFERENCES:
1. Lien EC, Dibble CC, Toker A. PI3K signaling in cancer: beyond AKT. Current opinion in cell biology. 2017;45:62-71.
2. Armitage P, Berry G, Matthews JN. Statistical methods in medical research. John Wiley & Sons; 2008 Apr 15.
3. King D, Yeomanson D, Bryant HE. PI3King the lock: targeting the PI3K/Akt/mTOR pathway as a novel therapeutic strategy in neuroblastoma. Journal of pediatric hematology/oncology. 2015 May 1;37(4):245-51.
4. Bagley CM, Devita VT, Berard CW, Canellos GP. Advanced lymphosarcoma: Intensive cyclical combination chemotherapy with cyclophosphamide, vincristine, and prednisone. Annals of internal medicine. 1972 Feb 1;76(2):227-34.
5. Fantin VR, St-Pierre J, Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer cell. 2006 Jun 13;9(6):425-34.
6. Yang W, Zheng Y, Xia Y, Ji H, Chen X, Guo F, Lyssiotis CA, Aldape K, Cantley LC, Lu Z. ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect. Nature cell biology. 2012 Dec;14(12):1295.
7. Semenza GL. Hypoxia‐inducible factor 1 and cancer pathogenesis. IUBMB life. 2008 Sep;60(9):591-7.
8. Koukourakis MI, Giatromanolaki A, Sivridis E, Gatter KC, Harris AL. Lactate dehydrogenase 5 expression in operable colorectal cancer: strong association with survival and activated vascular endothelial growth factor pathway—a report of the Tumour Angiogenesis Research Group. Journal of clinical oncology. 2006 Sep 10;24(26):4301-8.
9. Semenza GL, Roth PH, Fang HM, Wang GL. Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1. Journal of biological chemistry. 1994 Sep 23;269(38):23757-63.
10. Dang CV. c-Myc target genes involved in cell growth, apoptosis, and metabolism. Molecular and cellular biology. 1999 Jan 1;19(1):1-1.
11. Dang CV. The interplay between MYC and HIF in the Warburg effect. InOncogenes Meet Metabolism 2008 (pp. 35-53). Springer, Berlin, Heidelberg.
12. Zhao Y, Liu H, Riker AI, Fodstad O, Ledoux SP, Wilson GL, Tan M. Emerging metabolic targets in cancer therapy. Frontiers in bioscience: a journal and virtual library. 2011 Jan 1;16:1844.
13. Dang CV. The interplay between MYC and HIF in the Warburg effect. InOncogenes Meet Metabolism 2008 (pp. 35-53). Springer, Berlin, Heidelberg.
14. Dang CV, Le A, Gao P. MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clinical cancer research. 2009 Nov 1;15(21):6479-83.
15. Diaz LK, Sneige N. Estrogen receptor analysis for breast cancer: current issues and keys to increasing testing accuracy. Advances in anatomic pathology. 2005 Jan 1;12(1):10-9.
16. Damle NK, Frost P. Antibody-targeted chemotherapy with immunoconjugates of calicheamicin. Current opinion in pharmacology. 2003 Aug 1;3(4):386-90.
17. Dang CV. c-Myc target genes involved in cell growth, apoptosis, and metabolism. Molecular and cellular biology. 1999 Jan 1;19(1):1-1.
18. Dang CV. The interplay between MYC and HIF in the Warburg effect. InOncogenes Meet Metabolism 2008 (pp. 35-53). Springer, Berlin, Heidelberg.
19. Dang CV, Le A, Gao P. MYC-induced cancer cell energy metabolism and therapeutic opportunities. Clinical cancer research. 2009 Nov 1;15(21):6479-83.
20. DiLuna ML, King Jr JT, Knisely JP, Chiang VL. Prognostic factors for survival after stereotactic radiosurgery vary with the number of cerebral metastases. Cancer. 2007 Jan 1;109(1):135-45.
21. El Mjiyad N, Caro-Maldonado A, Ramirez-Peinado S, Munoz-Pinedo C. Sugar-free approaches to cancer cell killing. Oncogene. 2011 Jan;30(3):253.
22. Fentiman IS, Allen DS. γ-Glutamyl transferase and breast cancer risk. British journal of cancer. 2010 Jun;103(1):90.
23. Fantin VR, St-Pierre J, Leder P. Attenuation of LDH-A expression uncovers a link between glycolysis, mitochondrial physiology, and tumor maintenance. Cancer cell. 2006 Jun 13;9(6):425-34.
24. Halabi S, Small EJ, Kantoff PW, Kattan MW, Kaplan EB, Dawson NA, Levine EG, Blumenstein BA, Vogelzang NJ. Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer. Journal of Clinical Oncology. 2003 Apr 1;21(7):1232-7.
25. Gordan JD, Simon MC. Hypoxia-inducible factors: central regulators of the tumor phenotype. Current opinion in genetics & development. 2007 Feb 1;17(1):71-7.
26. Javadpour N, McIntire KR, Waldmann TA. Human chorionic gonadotropin (HCG) and alpha‐fetoprotein (AFP) in sera and tumor cells of patients with testicular seminoma. A prospective study. Cancer. 1978 Dec;42(6):2768-72.
27. Koukourakis MI, Giatromanolaki A, Simopoulos C, Polychronidis A, Sivridis E. Lactate dehydrogenase 5 (LDH5) relates to up-regulated hypoxia inducible factor pathway and metastasis in colorectal cancer. Clinical & experimental metastasis. 2005 Mar 1;22(1):25-30.
28. Kushner BH, LaQuaglia MP, Modak S, Cheung NK. Tumor lysis syndrome, neuroblastoma, and correlation between serum lactate dehydrogenase levels and MYCN‐amplification. Medical and pediatric oncology. 2003 Jul;41(1):80-2.
29. Leung SF, Chan KC, Ma BB, Hui EP, Mo F, Chow KC, Leung L, Chu KW, Zee B, Lo YM, Chan AT. Plasma Epstein–Barr viral DNA load at midpoint of radiotherapy course predicts outcome in advanced-stage nasopharyngeal carcinoma. Annals of Oncology. 2014 Mar 17;25(6):1204-8.
30. Sevinc A, Sari R, Fadillioglu E. The utility of lactate dehydrogenase isoenzyme pattern in the diagnostic evaluation of malignant and nonmalignant ascites. Journal of the National Medical Association. 2005 Jan;97(1):79.