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Loss of Imprinting of Insulin-Like Growth Factor 2 is Associated with Increased Risk of Primary Lung Cancer in the Central China Region

  • Zhang, Ming (Department of Pathology, Yantai Yantaishan Hospital) ;
  • Wu, Cui-Huan (Department of Pathology, Tongji Medical College and Institute of Pathology, Tongji Hospital) ;
  • Zhu, Xiao-Ling (Institute of Environmental Medicine and MOE Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology) ;
  • Wang, You-Jie (Institute of Environmental Medicine and MOE Key Lab for Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology)
  • Published : 2014.10.11

Abstract

Background: To determine the imprinting status of the IGF2 in Chinese patients with primary lung cancer and to analyze the clinical significance of the loss of imprinting (LOI) of IGF2. Materials and Methods: PCRRFLP and RT-PCR-RFLP were carried out to select heterozygous cases for the ApaI polymorphism within exon 9 of the IGF2 gene and further analyze IGF2 LOI in 64 lung cancer patients, respectively. Results: Of 64 lung cancer patients, 31 were heterozygous for IGF2. The positive rates of IGF2 LOI of lung cancer foci, matched paracancer tissues, and normal lung tissues were 77.4% (24/31), 61.3% (19/31), and 29.0% (9/31), respectively. The LOI differences for IGF2 among the three groups were statistically significant (${\chi}^2=15.267$, p=0.000), and the LOI frequency of IGF2 in normal lung tissue was significantly lower than that in lung cancer foci and paracancer tissues (${\chi}^2=14.577$, p=0.000; ${\chi}^2=6.513$, p=0.011). No statistical difference was observed between the lung tumor group and the matched paracancer group (${\chi}^2=1.897$, p=0.168). The prevalence of advanced clinical stages (${\chi}^2=2.379$; p=0.017) and lymph node metastasis (${\chi}^2=5.552$; p=0.018) was significantly higher for LOI-positive paracancer tissues than for LOI-negative paracancer tissues. Conclusions: IGF2 LOI is highly frequent in Chinese primary lung cancer patients, especially those with increased risk of lymph node metastasis and advanced clinical stages. IGF2 LOI may be an early epigenetic event in human lung carcinogenesis.

Keywords

References

  1. Brouwer-Visser J, Lee J, McCullagh K, et al (2014). Insulin-like growth factor 2 silencing restores taxol sensitivity in drug resistant ovarian cancer. PLoS One, 9, 100165. https://doi.org/10.1371/journal.pone.0100165
  2. Cui H, Horon IL, Ohlsson R, et al (1998). Loss of imprinting in normal tissue of colorectal cancer patients with microsatellite instability. Nat Med, 4, 1276-80. https://doi.org/10.1038/3260
  3. Cruz-Correa M, Cui H, Giardiello FM, et al (2004). Loss of imprinting of insulin growth factor II gene: a potential heritable biomarker for colon neoplasia predisposition. Gastroenterology, 126, 964-70. https://doi.org/10.1053/j.gastro.2003.12.051
  4. Feinberg AP, Tycko B (2004). The history of cancer epigenetics. Nat Rev Cancer, 4, 143-53. https://doi.org/10.1038/nrc1279
  5. Gao T, He B, Pan Y, et al (2014). H19 DMR methylation correlates to the progression of esophageal squamous cell carcinoma through IGF2 imprinting pathway. Clin Transl Oncol, 16, 410-7. https://doi.org/10.1007/s12094-013-1098-x
  6. Kaneda A, Wang CJ, Cheong R, et al (2007). Enhanced sensitivity to IGF-II signaling links loss of imprinting of IGF2 to increased cell proliferation and tumor risk. Proc Natl Acad Sci USA, 104, 20926-31. https://doi.org/10.1073/pnas.0710359105
  7. Kohda M, Hoshiya H, Katoh M, et al (2001). Frequent loss of imprinting of IGF2 and MEST in lung adenocarcinoma. Mol Carcinog, 31, 184-91. https://doi.org/10.1002/mc.1053
  8. Kondo M, Takahashi T (1996). Altered genomic imprinting in the IGF2 and H19 genes in human lung cancer. Nihon Rinsho, 54, 492-6.
  9. Linnerth NM, Baldwin M, Campbell C, et al (2005). IGF-II induces CREB phosphorylation and cell survival in human lung cancer cells. Oncogene, 24, 7310-9. https://doi.org/10.1038/sj.onc.1208882
  10. Livingstone C (2013). IGF2 and cancer. Endocr Relat Cancer, 20, 321-39. https://doi.org/10.1530/ERC-12-0240
  11. Nie ZL, Pan YQ, He BS, et al (2012). Gene therapy for colorectal cancer by an oncolytic adenovirus that targets loss of the insulin-like growth factor 2 imprinting system. Mol Cancer, 11, 86. https://doi.org/10.1186/1476-4598-11-86
  12. Nosho K, Yamamoto H, Taniguchi H, et al (2004). Interplay of insulin-like growth factor-II, insulin-like growth factor-I, insulin-like growth factor-I receptor, COX-2, and matrix metalloproteinase-7, play key roles in the early stage of colorectal carcinogenesis. Clin Cancer Res, 10, 7950-7. https://doi.org/10.1158/1078-0432.CCR-04-0875
  13. Pan Y, He B, Li T, et al (2010). Targeted tumor gene therapy based on loss of IGF2 imprinting. Cancer Biol Ther, 10, 290-8. https://doi.org/10.4161/cbt.10.3.12442
  14. Sakauchi F, Nojima M, Mori M, et al (2009). Serum insulin-like growth factors I and II, insulin-like growth factor binding protein-3 and risk of breast cancer in the Japan Collaborative Cohort study. Asian Pac J Cancer Prev, 10, 51-5.
  15. Sakatani T, Wei M, Katoh M, et al (2001). Epigenetic heterogeneity at imprinted loci in normal populations. Biochem Biophys Res Commun, 283, 1124-30. https://doi.org/10.1006/bbrc.2001.4916
  16. Tian F, Tang Z, Song G, et al (2012). Loss of imprinting of IGF2 correlates with hypomethylation of the H19 differentially methylated region in the tumor tissue of colorectal cancer patients. Mol Med Rep, 5, 1536-40.
  17. Vu TH, Nguyen AH, Hoffman AR (2010). Loss of IGF2 imprinting is associated with abrogation of long-range intrachromosomal interactions in human cancer cells. Hum Mol Genet, 19, 901-19. https://doi.org/10.1093/hmg/ddp558
  18. Woodson K, Flood A, Green L, et al (2004). Loss of insulin-like growth factor-II imprinting and the presence of screendetected colorectal adenomas in women. J Natl Cancer Inst, 96, 407-10. https://doi.org/10.1093/jnci/djh042
  19. Wu HK, Squire JA, Song Q, et al (1997). Promoter-dependent tissue-specific expressive nature of imprinting gene, insulinlike growth factor II, in human tissues. Biochem Biophys Res Commun, 233, 221-6. https://doi.org/10.1006/bbrc.1997.6431
  20. Woodson K, Flood A, Green L, et al (2004). Loss of Insulin-Like Growth Factor-II Imprinting and the Presence of Screen-Detected Colorectal Adenomas in Women. J Natl Cancer Inst, 96, 407-10. https://doi.org/10.1093/jnci/djh042
  21. Yang B, Wagner J, Damaschke N, et al (2014). A novel pathway links oxidative stress to loss of insulin growth factor-2 (IGF2) imprinting through NF-$\kappa$B activation. PLoS One, 18, 88052.
  22. Zhang M, Wu CH, Wang YJ, et al (2009). The relationship between HPV infection and the expression of protein insulin-like growth factor II in lung cancer and their clinical significance. Tumor, 29, 749-53.

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