Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

Expression Characteristics of Proteins of the Insulin-like Growth Factor Axis in Non-small Cell Lung Cancer Patients with Preexisting Type 2 Diabetes Mellitus

  • Ding, Jing (Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University) ;
  • Tang, Jie (Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University) ;
  • Chen, Xin (Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University) ;
  • Men, Hai-Tao (Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University) ;
  • Luo, Wu-Xia (Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University) ;
  • Du, Yang (Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University) ;
  • Ge, Jun (Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University) ;
  • Li, Cong (Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University) ;
  • Chen, Ye (Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University) ;
  • Cheng, Ke (Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University) ;
  • Qiu, Meng (Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University) ;
  • Liu, Ji-Yan (Department of Medical Oncology, Cancer Center, the State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University)
  • Published : 2013.10.30
Download PDF
⟨ Previous Next ⟩

Abstract

Background: Preexisting type 2 diabetes mellitus (T2DM) affects the prognosis and mortality of patients with some cancers. Insulin like growth factor (IGF) and insulin receptor (IR) signaling axes play important roles in both cancer and diabetes development. We aimed to explore the expression characteristics of proteins in IGF/IR axis in non-small cell lung cancer (NSCLC) cases with preexisting T2DM. Methods: Fifty-five NSCLC patients with preexisting T2DM were retrospectively included and matched by 55 NSCLC without diabetes at a 1:1 ratio. The expression of proteins in IGF/IR axis was detected by immunohistochemical staining. Clinicopathological data were collected to analyze their relationship with the protein expression. Results: Both IGF 1 receptor (IGF-1R) and insulin receptor substrate 2 (IRS-2) showed higher expression in the NSCLC with T2DM group, compared with those without T2DM. The high expression of IGF-1R and IRS-2 were found to be negatively associated with lymph node metastases and T staging in the T2DM group, respectively, and IRS-2 expression was also found more in the subgroup whose T2DM duration was more than 4 years. No difference was detected in the expression of IRS-1, IGF-1, IGF-2, IGFBP3, IR and mTOR between groups with or without T2DM. Conclusion: Our study found higher expression of IGF-1R and IRS-2 proteins in NSCLC patients with preexisting T2DM, and that there was an association with early stage NSCLC, which suggested that IGF signaling may play an important early event in development of NSCLC associated with diabetes.

Keywords

References

  1. Arif JM, Al-Saif AM, Al-Karrawi MA, Al-Sagair OA (2011). Causative relationship between diabetes mellitus and breast cancer in various regions of Saudi Arabia: an overview. Asian Pac J Cancer Prev, 12, 589-92.
  2. Atchison EA, Gridley G, Carreon JD, Leitzmann MF, McGlynn KA (2011). Risk of cancer in a large cohort of U.S. veterans with diabetes. Int J Cancer, 128, 635-43. https://doi.org/10.1002/ijc.25362
  3. Arcaro A (2013). Targeting the insulin-like growth factor-1 receptor in human cancer. Front Pharmacol, 4, 30.
  4. Barone BB, Yeh HC, Snyder CF, et al (2008). Long-term all-cause mortality in cancer patients with preexisting diabetes mellitus: a systematic review and meta-analysis. JAMA, 300, 2754-64. https://doi.org/10.1001/jama.2008.824
  5. Chott A, Sun Z, Morganstern D, et al (1999). Tyrosine kinases expressed in vivo by human prostate cancer bone marrow metastases and loss of the type 1 insulin-like growth factor receptor. Am J Pathol, 155, 1271-9. https://doi.org/10.1016/S0002-9440(10)65229-7
  6. Currie CJ, Poole CD, Jenkins-Jones S, et al (2012). Mortality after incident cancer in people with and without type 2 diabetes: impact of metformin on survival. Diabetes Care, 35, 299-304. https://doi.org/10.2337/dc11-1313
  7. Elena JW, Steplowski E, Yu K, et al (2013). Diabetes and risk of pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium. Cancer Causes Control, 24, 13-25. https://doi.org/10.1007/s10552-012-0078-8
  8. Fidler MJ, Shersher DD, Borgia JA, Bonomi P (2012). Targeting the insulin-like growth factor receptor pathway in lung cancer: problems and pitfalls. Ther Adv Med Oncol, 4, 51-60. https://doi.org/10.1177/1758834011427576
  9. Ferguson R, Gallagher EJ, Cohen D, et al (2013). Hyperinsulinemia promotes metastasis to the lung in a mouse model of Her2/Neu-mediated breast cancer. Endocr Relat Cancer, 20, 391-401. https://doi.org/10.1530/ERC-12-0333
  10. Gibson SL, Ma Z, Shaw LM, et al (2007). Divergent roles for IRS-1 and IRS-2 in breast cancer metastasis. Cell Cycle, 6, 631-7. https://doi.org/10.4161/cc.6.6.3987
  11. Herberger B, Puhalla H, Lehnert M (2007). Activated mammalian target of rapamycin is an adverse prognostic factor in patients with biliary tract adenocarcinoma. Clin Cancer Res, 13, 4795-9. https://doi.org/10.1158/1078-0432.CCR-07-0738
  12. Hanbali A, Al-Khasawneh K, Cole-Johnson C, Divine G, Haytham Ali (2007). Protective effect of diabetes against metastasis in patients with non-small cell lung cancer. Arch Intern Med, 167, 513.
  13. He J, Stram DO, Kolonel LN, et al (2010). The association of diabetes with colorectal cancer risk: the Multiethnic Cohort. Br J Cancer, 103, 120-6. https://doi.org/10.1038/sj.bjc.6605721
  14. Hardefeldt PJ, Edirimanne S, Eslick GD (2012). Diabetes increases the risk of breast cancer: a meta-analysis. Endocr Relat Cancer, 19, 793-803. https://doi.org/10.1530/ERC-12-0242
  15. Hwang A, Narayan V, Yang YX (2013). Type 2 diabetes mellitus and survival in pancreatic adenocarcinoma: a retrospective cohort study. Cancer, 119, 404-10. https://doi.org/10.1002/cncr.27731
  16. Jackson JG, Zhang X, Yoneda T, Yee D (2001). Regulation of breast cancer cell motility by insulin receptor substrate-2 (IRS-2) in metastatic variants of human breast cancer cell lines. Oncogene, 20, 7318-25. https://doi.org/10.1038/sj.onc.1204920
  17. Kornmann M, Maruyama H, Bergmann U, et al (1998). Enhanced expression of the insulin receptor substrate-2 docking protein in human pancreatic cancer. Cancer Res, 58, 4250-4.
  18. Kurishima K, Satoh H (2012). Prolonged survival in lung cancer patients with diabetes mellitus. J Thorac Oncol, 7, e17-8. https://doi.org/10.1097/JTO.0b013e3182614877
  19. LeRoith D, Roberts CT (2003). The insulin-like growth factor system and cancer. Cancer Letters, 195, 127-37. https://doi.org/10.1016/S0304-3835(03)00159-9
  20. Lee JY, Jeon I, Lee JM, Yoon JM, Park SM (2013). Diabetes mellitus as an independent risk factor for lung cancer: A meta-analysis of observational studies. Eur J Cancer, 49, 2411-23. https://doi.org/10.1016/j.ejca.2013.02.025
  21. Pavelic J, Krizanac S, Kapitanovic S, et al (2005). The consequences of insulin-like growth factors/receptors dysfunction in lung cancer. Am J Respir Cell Mol Biol, 32, 65-71. https://doi.org/10.1165/rcmb.2004-0232OC
  22. Rajpathak SN, Gunter MJ, Wylie-Rosett J,et al (2009). The role of insulin-like growth factor-I and its binding proteins in glucose homeostasis and type 2 diabetes. Diabetes Metab Res Rev, 25, 3-12. https://doi.org/10.1002/dmrr.919
  23. Satyamoorthy K., Li G, Vaidya B, Patel D, Herlyn M (2001). Insulin-like growth factor-1 induces survival and growth of biologically early melanoma cells through both the mitogenactivated protein kinase and beta-catenin pathways. Cancer Res, 61, 7318-24.
  24. Shaw LM (2011). The insulin receptor substrate (IRS) proteins: At the intersection of metabolism and cancer. Cell Cycle, 10, 1750-6. https://doi.org/10.4161/cc.10.11.15824
  25. Siegel R, Naishadham D, Jemal A, et al (2013). Cancer statistics, 2013. CA Cancer J Clin, 63, 11-30. https://doi.org/10.3322/caac.21166
  26. Tan BX, Yao WX, Ge J, et al (2011). Prognostic influence of metformin as first-line chemotherapy for advanced non-small cell lung cancer in patients with type 2 diabetes. Cancer, 117, 5103-11. https://doi.org/10.1002/cncr.26151
  27. Varlotto J, Medford-Davis LN, Recht A, et al (2012). Confirmation of the role of diabetes in the local recurrence of surgically resected non-small cell lung cancer. Lung Cancer, 75, 381-90. https://doi.org/10.1016/j.lungcan.2011.07.019
  28. Wu J, Tseng YD, Xu CF, et al (2008). Structural and biochemical characterization of the KRLB region in insulin receptor substrate-2. Nat Struct Mol Biol, 15, 251-8. https://doi.org/10.1038/nsmb.1388
  29. Wang C, Wang X, Gong G, et al (2012). Increased risk of hepatocellular carcinoma in patients with diabetes mellitus: a systematic review and meta-analysis of cohort studies. Int J Cancer, 130, 1639-48. https://doi.org/10.1002/ijc.26165
  30. Wang T, Ning G, Bloomgarden Z (2013). Diabetes and Cancer Relationships. J Diabetes, doi: 10.1111/1753-0407.12057
  31. Walker JJ, Brewster DH, Colhoun HM, et al (2013). Cause-specific mortality in Scottish patients with colorectal cancer with and without type 2 diabetes (2000-2007). Diabetologia, 56, 1531-41. https://doi.org/10.1007/s00125-013-2917-x
  32. Zhang ZH, Su PY, Hao JH, Sun YH (2013). The role of preexisting diabetes mellitus on incidence and mortality of endometrial cancer: a meta-analysis of prospective cohort studies. Int J Gynecol Cancer, 23, 294-303. https://doi.org/10.1097/IGC.0b013e31827b8430

Cited by

  1. RNA-Seq and Network Analysis Revealed Interacting Pathways in TGF-β-Treated Lung Cancer Cell Lines vol.13s5, pp.1176-9351, 2014, https://doi.org/10.4137/CIN.S14073
  2. Lack of any Prognostic Role of Insulin-Like Growth Factor-1 Receptor in Non-Small Cell Lung Cancer vol.15, pp.14, 2014, https://doi.org/10.7314/APJCP.2014.15.14.5753
  3. Anti-Diabetic Medications Do Not Influence Risk of Lung Cancer in Patients with Diabetes Mellitus: a Systematic Review and Meta-analysis vol.15, pp.16, 2014, https://doi.org/10.7314/APJCP.2014.15.16.6863
  4. Role of Hyperinsulinemia in Increased Risk of Prostate Cancer: A Case Control Study from Kathmandu Valley vol.15, pp.2, 2014, https://doi.org/10.7314/APJCP.2014.15.2.1031
  5. Higher Expression of Proteins in IGF/IR Axes in Colorectal Cancer is Associated with Type 2 Diabetes Mellitus vol.22, pp.4, 2016, https://doi.org/10.1007/s12253-016-0065-6
  6. Correlation of the expressions of IGF1R-RACK1-STAT3 and Bcl-xl in nasopharyngeal carcinoma with the clinicopathological features and prognosis of nasopharyngeal carcinoma pp.07302312, 2017, https://doi.org/10.1002/jcb.26354
  7. The Peroxisome Proliferator-Activated Receptor (PPAR) α Agonist Fenofibrate Suppresses Chemically Induced Lung Alveolar Proliferative Lesions in Male Obese Hyperlipidemic Mice vol.15, pp.5, 2014, https://doi.org/10.3390/ijms15059160
  8. Insulin-like growth factor 1 receptor expression in advanced non-small-cell lung cancer and its impact on overall survival vol.51, pp.2, 2017, https://doi.org/10.1515/raon-2017-0020
  9. in High Glucose-Induced SHSY-5Y Cells pp.1557-7430, 2018, https://doi.org/10.1089/dna.2018.4336