대장암에서 LDH-5의 발현: 예후 및 종양 신생혈관 형성과의 관계 = Expression of LDH-5 in Colorectal Carcinomas: Correlation with Prognosis and Tumor Angiogenesis

다국어 초록 (Multilingual Abstract)

Purpose: Lactate dehydrogenase-5 (LDH-5) is one of five isoenzymes and is the most important for anaerobic glycolysis.
LDH-5 is transcriptionally regulated by hypoxia-inducible factor (HIF). HIF plays a role in the response to hypoxia by activating genes involved in vascular remodeling, cell proliferation, and erythropoiesis. In this study, we investigated the clinicopathologic significance and angiogenesis of LDH-5 expression in colorectal cancer.
Methods: We retrospectively reviewed the medical records of 83 patients with colorectal cancer who underwent a surgical resection at Soonchunhyang Cheonan Hospital from January 2001 to December 2003. LDH-5 and HIF-1a protein expressions were evaluated in 83 human colorectal cancer specimens. These factors were related to TNM stage, lymph node metastasis,vascular, neural, and lymphatic invasion, and prognosis.
Results: LDH-5 was positive in 66% (55 patients) of the tumors, and HIF-1a was positive in 66% (55 patients) of the tumors.
LDH-5 expression was significantly associated with HIF-1a protein expression (P<0.001). Also, LDH-5 expression was significantly associated with TNM stage and lymph node metastasis (P<0.001) while HIF-1a expression was significantly associated with TNM stage (P<0.001), lymph node metastasis (P<0.001), vascular invasion (P=0.011), and lymphatic invasion (P=0.005).
The survival of the patients with high LDH-5 expression was worse than that of patients with low LDH-5 expression (P=0.032).
Conclusion: Our study shows a high expression of LDH-5 in colorectal cancer. The up-regulation of LDH-5 parallels an increase in HIF-1a expression. The immunohistochemical assessment of tissue LDH-5 and HIF-1a provides important prognostic information for colorectal carcinomas.

참고문헌 (Reference)

1 최윤영, "대장암에서의 Hypoxia Inducible Factor-1α (HIF-1α) 및 Vascular Endothelial Growth Factor (VEGF): 예후 및 종양표지자로서의 가능성" 대한대장항문학회 24 (24): 337-344, 2008

2 Koukourakis MI, "Tumour Angiogenesis Research Group. 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" 24 : 4301-4308, 2006

3 Hockel M, "Tumor hypoxia: definitions and current clinical, biologic, and molecular aspects" 93 : 266-276, 2001

4 Semenza GL, "Transcriptional regulation of genes encoding glycolytic enzymes by hypoxia-inducible factor 1" 269 : 23757-23763, 1994

5 Seagroves TN, "Transcription factor HIF-1 is a necessary mediator of the pasteur effect in mammalian cells" 21 : 3436-3444, 2001

6 Semenza G, "Signal transduction to hypoxia-inducible factor 1" 64 : 993-998, 2002

7 Semenza GL, "Regulation of mammalian O2 homeostasis by hypoxiainducible factor 1" 15 : 551-578, 1999

8 Tas F, "Prognostic factors in pancreatic carcinoma: serum LDH levels predict survival in metastatic disease" 24 : 547-550, 2001

9 Zhong H, "Overexpression of hypoxia-inducible factor 1a in common human cancers and their metastases" 59 : 5830-5835, 1999

10 Warburg O, "On the origin of cancer cells" 123 : 309-314, 1956

11 "National Cancer Information Center"

12 Holbrook JJ, "Lactate dehydrogenase. In: Boyer PD, editor. The Enzymes. 3rd ed" Academic Press 191-292, 1975

13 Kolev Y, "Lactate dehydrogenase-5 (LDH-5) expression in human gastric cancer: association with hypoxiainducible factor (HIF-1alpha) pathway, angiogenic factors production and poor prognosis" 15 : 2336-2344, 2008

14 Kolev Y, "Lactate dehydrogenase-5 (LDH-5) expression in human gastric cancer: association with hypoxiainducible factor (HIF-1a) pathway, angiogenic factors production and poor prognosis" 15 : 2336-2344, 2008

15 Koukourakis MI, "Lactate dehydrogenase isoenzymes 1 and 5: differential expression by neoplastic and stromal cells in non-small cell lung cancer and other epithelial malignant tumors" 24 : 199-202, 2003

16 Semenza GL, "Hypoxiainducible nuclear factors bind to an enhancer element located 3′to the human erythropoietin gene" 88 : 5680-5684, 1991

17 Griffiths EA, "Hypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastrooesophageal adenocarcinomas" 96 : 95-103, 2007

18 Griffiths EA, "Hypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastrooesophageal adenocarcinomas" 96 : 95-103, 2007

19 Lu H, "Hypoxia-inducible factor 1 activation by aerobic glycolysis implicates the Warburg effect in carcinogenesis" 277 : 23111-23115, 2002

20 Semenza GL, "HIF-1: mediator of physiological and pathophysiological responses to hypoxia" 88 : 1474-1480, 2000

21 Brizel DM, "Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer" 51 : 349-353, 2001

22 Wang V, "Differential gene up-regulation by hypoxia-inducible factor-1alpha and hypoxia-inducible factor-2alpha in HEK293T cells" 65 : 3299-3306, 2005

23 Yuce K, "Diagnostic and prognostic value of serum and peritoneal fluid lactate dehydrogenase in epithelial ovarian cancer" 22 : 228-232, 2001

24 Stubbs M, "Causes and consequences of tumour acidity and implications for treatment" 6 : 15-19, 2000