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http://dx.doi.org/10.7314/APJCP.2013.14.6.3613

Expression and Significance of Hypoxia Inducible Factor-1α and Lysyl Oxidase in Non-small Cell Lung Cancer  

Ping, Wei (Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology)
Jiang, Wen-Yang (Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology)
Chen, Wen-Shu (Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology)
Sun, Wei (Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology)
Fu, Xiang-Ning (Department of Thoracic Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology)
Publication Information
Asian Pacific Journal of Cancer Prevention / v.14, no.6, 2013 , pp. 3613-3618 More about this Journal
Abstract
Object: To detect expression of hypoxia inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$) and lysyl oxidase (LOX) in non-small cell lung cancer (NSCLC) and explore their roles in prognosis. Methods: The mRNA levels of HIF-$1{\alpha}$ and LOX were investigated by real-time reverse-transcriptase polymerase chain reaction in 40 cases of tumour and paired normal tissues. In addition, protein expression of HIF-$1{\alpha}$ and LOX was examined by immunohistochemistry in 82 cases of tumour and 45 paired normal tissues. The relationship between HIF-$1{\alpha}$ or LOX and clinicopathologic characteristics, as well as the correlation between HIF-$1{\alpha}$ and LOX, were also examined. Kaplan-Meier survival curves and the log-rank test were used to analyze progression-free survival. Results: HIF-$1{\alpha}$ or LOX mRNA levels in tumor tissues was significantly higher than those in paired normal tissues (p<0.01). Positive HIF-$1{\alpha}$ or LOX protein expression in tumor tissues was noted in 46/82 (56.1%) and 49/82 (59.8%) of the cases, respectively, being significantly higher than those in paired normal tissues (p<0.05). There was significant correlation between the expression of HIF-$1{\alpha}$ or LOX and tumor size, lymph node metastasis and pathological stage (p<0.05). The expression of HIF-$1{\alpha}$ and LOX had a significant inverse impact on survival of patients with NSCLC. Conclusion: HIF-$1{\alpha}$ and LOX may play a pivotal role in the development of NSCLC, and may act in synergy to promote the progression of NSCLC.
Keywords
HIF-$1{\alpha}$; LOX; NSCLC; prognosis;
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1 al-Kattan K, Sepsas E, Fountain SW, et al (1997). Disease recurrence after resection for stage I lung cancer. Eur J Cardiothorac Surg, 12, 380-4.   DOI   ScienceOn
2 Albinger-Hegyi A, Stoeckli SJ, Schmid S, et al (2010). Lysyl oxidase expression is an independent marker of prognosis and a predictor of lymph node metastasis in oral and oropharyngeal squamous cell carcinoma (OSCC). Int J Cancer, 126, 2653-62.
3 Bachtiary B, Schindl M, Potter R, et al (2003). Overexpression of hypoxia-inducible factor 1alpha indicates diminished response to radiotherapy and unfavorable prognosis in patients receiving radical radiotherapy for cervical cancer. Clin Cancer Res, 9, 2234-40.
4 Baker AM, Bird D, Lang G, et al (2013). Lysyl oxidase enzymatic function increases stiffness to drive colorectal cancer progression through FAK. Oncogene, 32, 1863-8.   DOI   ScienceOn
5 Birner P, Schindl M, Obermair A, et al (2000). Overexpression of hypoxia-inducible factor 1alpha is a marker for an unfavorable prognosis in early-stage invasive cervical cancer. Cancer Res, 60, 4693-6.
6 Cheng JC, Klausen C, Leung PC (2013). Hypoxia-inducible factor 1 alpha mediates epidermal growth factor-induced down-regulation of E-cadherin expression and cell invasion in human ovarian cancer cells. Cancer Lett, 329, 197-206.   DOI   ScienceOn
7 Erler JT, Bennewith KL, Nicolau M, et al (2006). Lysyl oxidase is essential for hypoxia-induced metastasis. Nature, 440, 1222-6.   DOI   ScienceOn
8 Gao Y, Xiao Q, Ma H, et al (2010). LKB1 inhibits lung cancer progression through lysyl oxidase and extracellular matrix remodeling. Proc Natl Acad Sci USA, 107, 18892-7.   DOI   ScienceOn
9 Giatromanolaki A, Koukourakis MI, Sivridis E, et al (2001). Relation of hypoxia inducible factor 1 alpha and 2 alpha in operable non-small cell lung cancer to angiogenic/molecular profile of tumours and survival. Br J Cancer, 85, 881-90.   DOI   ScienceOn
10 Gu CD, Osaki T, Oyama T, et al (2002). Detection of micrometastatic tumor cells in pN0 lymph nodes of patients with completely resected nonsmall cell lung cancer: impact on recurrence and Survival. Ann Surg, 235, 133-9.   DOI   ScienceOn
11 Hiraki M, Kitajima Y, Kai K, et al (2012). Knockdown of hypoxia-inducible factor-1alpha accelerates peritoneal dissemination via the upregulation of MMP-1 expression in gastric cancer cell lines. Exp Ther Med, 4, 355-62.
12 Hirami Y, Aoe M, Tsukuda K, et al (2004). Relation of epidermal growth factor receptor, phosphorylated-Akt, and hypoxiainducible factor-1alpha in non-small cell lung cancers. Cancer Lett, 214, 157-64.   DOI   ScienceOn
13 Hung JJ, Yang MH, Hsu HS, et al (2009). Prognostic significance of hypoxia-inducible factor-1alpha, TWIST1 and Snail expression in resectable non-small cell lung cancer. Thorax, 64, 1082-9.   DOI   ScienceOn
14 Lapointe J, Li C, Higgins JP, et al (2004). Gene expression profiling identifies clinically relevant subtypes of prostate cancer. Proc Natl Acad Sci USA, 101, 811-6.   DOI   ScienceOn
15 Lee CH, Lee MK, Kang CD, et al (2003). Differential expression of hypoxia inducible factor-1 alpha and tumor cell proliferation between squamous cell carcinomas and adenocarcinomas among operable non-small cell lung carcinomas. J Korean Med Sci, 18, 196-203.   과학기술학회마을   DOI   ScienceOn
16 Le QT, Kong C, Lavori PW, et al (2007). Expression and prognostic significance of a panel of tissue hypoxia markers in head-and-neck squamous cell carcinomas. Int J Radiat Oncol Biol Phys, 69, 167-75.   DOI   ScienceOn
17 Sahlgren C, Gustafsson MV, Jin S, et al (2008). Notch signaling mediates hypoxia-induced tumor cell migration and invasion. Proc Natl Acad Sci USA, 105, 6392-7.   DOI   ScienceOn
18 Park S, Ha SY, Cho HY, et al (2011). Prognostic implications of hypoxia-inducible factor-1alpha in epidermal growth factor receptor-negative non-small cell lung cancer. Lung Cancer, 72, 100-7.   DOI   ScienceOn
19 Payne SL, Hendrix MJ, Kirschmann DA (2007). Paradoxical roles for lysyl oxidases in cancer--a prospect. J Cell Biochem, 101, 1338-54.   DOI   ScienceOn
20 Pez F, Dayan F, Durivault J, et al (2011). The HIF-1-inducible lysyl oxidase activates HIF-1 via the Akt pathway in a positive regulation loop and synergizes with HIF-1 in promoting tumor cell growth. Cancer Res, 71, 1647-57.   DOI
21 Schietke R, Warnecke C, Wacker I, et al (2010). The lysyl oxidases LOX and LOXL2 are necessary and sufficient to repress E-cadherin in hypoxia: insights into cellular transformation processes mediated by HIF-1. J Biol Chem, 285, 6658-69.   DOI   ScienceOn
22 Schito L, Rey S, Tafani M, et al (2012). Hypoxia-inducible factor 1-dependent expression of platelet-derived growth factor B promotes lymphatic metastasis of hypoxic breast cancer cells. Proc Natl Acad Sci USA, 109, E2707-16.   DOI
23 Siegel R, DeSantis C, Virgo K, et al (2012). Cancer treatment and survivorship statistics, 2012. CA Cancer J Clin, 62, 220-41.   DOI
24 Siegel R, Ward E, Brawley O, et al (2011). Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA Cancer J Clin, 61, 212-36.   DOI
25 Stassar MJ, Devitt G, Brosius M, et al (2001). Identification of human renal cell carcinoma associated genes by suppression subtractive hybridization. Br J Cancer, 85, 1372-82.   DOI   ScienceOn
26 Volm M, Koomagi R (2000). Hypoxia-inducible factor (HIF-1) and its relationship to apoptosis and proliferation in lung cancer. Anticancer Res, 20, 1527-33.
27 Stewart GD, Nanda J, Brown DJ, et al (2009). NO-sulindac inhibits the hypoxia response of PC-3 prostate cancer cells via the Akt signalling pathway. Int J Cancer, 124, 223-32.   DOI   ScienceOn
28 Swinson DE, Jones JL, Cox G, et al (2004). Hypoxia-inducible factor-1 alpha in non small cell lung cancer: relation to growth factor, protease and apoptosis pathways. Int J Cancer, 111, 43-50.   DOI   ScienceOn
29 Tammali R, Saxena A, Srivastava SK, et al (2011). Aldose reductase inhibition prevents hypoxia-induced increase in hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) by regulating 26 S proteasome-mediated protein degradation in human colon cancer cells. J Biol Chem, 286, 24089-100.   DOI   ScienceOn
30 Wei L, Song XR, Sun JJ, et al (2012). Lysyl oxidase may play a critical role in hypoxia-induced NSCLC cells invasion and migration. Cancer Biother Radiopharm, 27, 672-7.   DOI   ScienceOn
31 Wilgus ML, Borczuk AC, Stoopler M, et al (2011). Lysyl oxidase: a lung adenocarcinoma biomarker of invasion and survival. Cancer, 117, 2186-91.   DOI   ScienceOn
32 Wong CC, Gilkes DM, Zhang H, et al (2011). Hypoxia-inducible factor 1 is a master regulator of breast cancer metastatic niche formation. Proc Natl Acad Sci USA, 108, 16369-74.   DOI   ScienceOn
33 Wong CC, Zhang H, Gilkes DM, et al (2012). Inhibitors of hypoxia-inducible factor 1 block breast cancer metastatic niche formation and lung metastasis. J Mol Med (Berl), 90, 803-15.   DOI
34 Woznick AR, Braddock AL, Dulai M, et al (2005). Lysyl oxidase expression in bronchogenic carcinoma. Am J Surg, 189, 297-301.   DOI   ScienceOn
35 Zhong H, De Marzo AM, Laughner E, et al (1999). Overexpression of hypoxia-inducible factor 1alpha in common human cancers and their metastases. Cancer Res, 59, 5830-5.
36 Zhang JJ, Wu HS, Wang L, et al (2010). Expression and significance of TLR4 and HIF-1alpha in pancreatic ductal adenocarcinoma. World J Gastroenterol, 16, 2881-8.   DOI   ScienceOn
37 Zhao T, Gao S, Wang X, et al (2012). Hypoxia-inducible factor-1alpha regulates chemotactic migration of pancreatic ductal adenocarcinoma cells through directly transactivating the CX3CR1 gene. PLoS One, 7, e43399.   DOI