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GOLPH3, a Good Prognostic Indicator in Early-stage NSCLC Related to Tumor Angiogenesis

  • Lu, Ming (Department of Thoracic Surgery, Qilu Hospital, Shandong University) ;
  • Tian, Yu (Department of Thoracic Surgery, Qilu Hospital, Shandong University) ;
  • Yue, Wei-Ming (Department of Thoracic Surgery, Qilu Hospital, Shandong University) ;
  • Li, Lin (Department of Thoracic Surgery, Qilu Hospital, Shandong University) ;
  • Li, Shu-Hai (Department of Thoracic Surgery, Qilu Hospital, Shandong University) ;
  • Qi, Lei (Department of Thoracic Surgery, Qilu Hospital, Shandong University) ;
  • Hu, Wen-Si (Department of Thoracic Surgery, Qilu Hospital, Shandong University) ;
  • Gao, Cun (Department of Thoracic Surgery, Qilu Hospital, Shandong University) ;
  • Si, Li-Bo (Department of Thoracic Surgery, Qilu Hospital, Shandong University) ;
  • Tian, Hui (Department of Thoracic Surgery, Qilu Hospital, Shandong University)
  • Published : 2014.07.30

Abstract

Background: Golgi phosphoprotein-3 (GOLPH3) is implicated in cancer development and progression. The aim of this study was to evaluate the prognostic significance of GOLPH3 protein and its association with tumor angiogenesis in patients with early-stage NSCLC. Materials and Methods: Immunohistochemistry was performed to determine GOLPH3 protein expression and allow assessment of intratumoral microvessel density (MVD) by counting CD-34 positive immunostained endothelial cells. Correlations of expression with MVD, clinicopathologic features and clinical prognosis were analyzed. Results: A notably higher level of GOLPH3 expression was found in early-stage NSCC tissues at the protein level. However, we do not find any correlation between GOLPH3 expression and clinicopathologic features (p>0.05), although higher MVD was positively associated with GOLPH3 overexpression (p<0.001). Expression of GOLPH3 was found to be an independent prognostic factor in early-stage NSCLC patients, those expressing high levels of GOLPH3 exhibiting a substantially lower 5-year overall survival than GOLPH3-negative patients (adjusted HR =1.899, 95% CI: 1.021-3.532, p=0.043). Conclusions: High expression of the GOLPH3 protein is common in early-stage NSCC, and is closely associated with tumor progression, increased tumor angiogenesis, and poor survival. We conclude a possibility of its use as a diagnostic and prognostic marker in early-stage NSCC patients.

Keywords

References

  1. Arriagada R, Bergman B, Dunant A, et al (2004). Cisplatin-based adjuvant chemotherapy in patients with completely resected non- small-cell lung cancer. N Engl J Med, 350, 351-60. https://doi.org/10.1056/NEJMoa031644
  2. Brognard J, Clark AS, Ni Y et al (2001). Akt/protein kinase B is constitutively active in non-small cell lung cancer cells and promotes cellular survival and resistance to chemotherapy and radiation. Cancer Res, 61, 3986-97.
  3. Bohm M, Wieland I, Schmidt C, et al (2001). Loss of heterozygosity on chromosome 5p13-12 predicts adverse prognosis in advanced bladder cancer independent of tumor stage and grade. J Urol , 168, 2655-58.
  4. Butler JM, Kobayashi H, Rafii S (2010). Instructive role of the vascular niche in promoting tumour growth and tissue repair by angiocrine factors. Nat Rev Cancer, 10, 138-46. https://doi.org/10.1038/nrc2791
  5. Crino' L, Weder W, van Meerbeeck J, et al (2001). Early stage and locally advanced (non-metastatic) non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol, 21, 103-15.
  6. Dominik Wolf, Anna M.Wolf, Holger Rumpold, et al (2005). The expression of the regulatory T cell-specific forkhead box transcription factor Foxp3 is associated with poor prognosis in ovarian cancer. Clin Cancer Res, 11, 8326-31. https://doi.org/10.1158/1078-0432.CCR-05-1244
  7. Fry WA, Philips JL and Menck HR (1999). Ten-year survey of lung cancer treatment and survival in hospitals in the United States: a national cancer data base report. Cancer, 86, 1867-76. https://doi.org/10.1002/(SICI)1097-0142(19991101)86:9<1867::AID-CNCR31>3.0.CO;2-9
  8. Gao W, Liu L, Lu X, et al (2011). Circulating microRNAs: possible prediction biomarkers for personalized therapy of non-small-cell lung carcinoma. Clin Lung Cancer, 12, 14-7. https://doi.org/10.3816/CLC.2011.n.001
  9. Gorringe KL, Boussioutas A, Bowtell DD (2005). Novel regions of chromosomal amplification at 6p21, 5p13, and 12q14 in gastric cancer identified by array comparative genomic hybridization. Genes Chromosomes Cancer, 42, 247-59. https://doi.org/10.1002/gcc.20136
  10. Guertin D A, Sabatini D M (2007). Defining the role of mTOR in cancer. Cancer cell, 12, 9-22. https://doi.org/10.1016/j.ccr.2007.05.008
  11. Hanahan D, Weinberg RA (2011). Hallmarks of cancer: the next generation. Cell, 144, 646-74. https://doi.org/10.1016/j.cell.2011.02.013
  12. Hua X, Yu L, Pan W, et al (2012). Increased expression of Golgi phosphoprotein-3 is associated with tumor aggressiveness and poor prognosis of prostate cancer. Diagn Pathol , 7, 127. https://doi.org/10.1186/1746-1596-7-127
  13. Hu BS, Hu H, Zhu CY, et al (2013). Overexpression of GOLPH3 is associated with poor clinical outcome in gastric cancer. Tumour Biol, 34, 515-20. https://doi.org/10.1007/s13277-012-0576-z
  14. Li H, Guo L, Chen SW, et al (2012). GOLPH3 overexpression correlates with tumor progression and poor prognosis in patients with clinically N0 oral tongue cancer. J Transl Med, 10, 168. https://doi.org/10.1186/1479-5876-10-168
  15. Mineo T C, Ambrogi V, Baldi A, et al (2004). Prognostic impact of VEGF, CD31, CD34, and CD105 expression and tumour vessel invasion after radical surgery for IB-IIA non-small cell lung cancer. J Clin Pathol, 57, 591-97. https://doi.org/10.1136/jcp.2003.013508
  16. Nakashima KN, Asoh S, Ishibashi Y, et al (2005). MIDAS/ GPP34, a nuclear gene product, regulates total mitochondrial mass in response to mitochondrial dysfunction. J Cell Sci, 118, 5357-67. https://doi.org/10.1242/jcs.02645
  17. Pignon JP, Tribodet H, Scagliotti GV, et al, on behalf of the LACE Collaborative Group (2006). Lung Adjuvant Cisplatin Evaluation (LACE): a pooled analysis of five randomized clinical trials including 4, 584 patients. J Clin Oncol, 24, 366s (abstract 7008).
  18. Ren H, Tang X, Lee JJ, et al (2004). Expression of hepatomaderived growth factor is a strong prognostic predictor for patients with early-stage non-small-cell lung cancer. J Clin Oncol, 22, 3230-37. https://doi.org/10.1200/JCO.2004.02.080
  19. Snyder CM, Mardones GA, Ladinsky MS, et al (2006). GMx33 associates with the trans-Golgi matrix in a dynamic manner and sorts within tubules exiting the Golgi. Mol Biol Cell, 17, 511-24.
  20. Smith CB, Kelley AS, Meier DE (2010). Evidence for new standard of care in non-small cell lung cancer patients. Semin Thorac Cardiovasc Surg , 22, 193-4. https://doi.org/10.1053/j.semtcvs.2010.10.002
  21. Scott KL, Kabbarah O, Liang MC, et al (2009). GOLPH3 modulates mTOR signalling and rapamycin sensitivity in cancer. Nature, 459, 1085-90. https://doi.org/10.1038/nature08109
  22. TravisWD (2011). Pathology of lung cancer. Clin Chest Med, 32, 669-92. https://doi.org/10.1016/j.ccm.2011.08.005
  23. Vermeulen PB, Gasparini G, Fox SB, et al (2002). Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer, 38, 1564-79. https://doi.org/10.1016/S0959-8049(02)00094-1
  24. Wu CC, Taylor RS, Lane DR, et al (2000). GMx33: a novel family of trans-Golgi proteins identified by proteomics. Traffic, 1, 963-75.
  25. Winton T, Livingston R, Johnson D, et al (2005). Vinorelbine plus cisplatin vs observation in resected non-small-cell lung cancer. N Engl J Med, 352, 2589-97. https://doi.org/10.1056/NEJMoa043623
  26. Wang JH, Chen XT, Wen ZS, et al (2012). High expression of GOLPH3 in esophageal squamous cell carcinoma correlates with poor prognosis. PLoS One, 7, 45622. https://doi.org/10.1371/journal.pone.0045622
  27. Wang Q, Wang X, Zhang C B (2013). Lentivirus mediated GOLPH3 shRNA inhibits growth and metastasis of esophageal squamous cancer. Asian Pac J Cancer Prev, 14, 5391-96. https://doi.org/10.7314/APJCP.2013.14.9.5391
  28. Yokoi S, Yasui K, Saito-Ohara F, et al (2002). A novel target gene, SKP2, within the 5p13 amplicon that is frequently detected in small cell lung cancers. Am J Pathol, 161, 207-16. https://doi.org/10.1016/S0002-9440(10)64172-7
  29. Yano T, Tanikawa S, Fujie T, et al (2002). Vascular endothelial growth factor expression and neovascularisation in nonsmall cell lung cancer. Eur J Cancer, 36, 601-9.
  30. Zeng Z, Lin H, Zhao X, et al (2012). Overexpression of GOLPH3 promotes proliferation and tumorigenicity in breast cancer via suppression of the FOXO1 transcription factor. Clin Cancer Res, 18, 4059-69. https://doi.org/10.1158/1078-0432.CCR-11-3156
  31. Zhou J, Xu T, Qin R, et al (2012). Overexpression of Golgi phosphoprotein-3 (GOLPH3) in glioblastoma multiforme is associated with worse prognosis. J Neurooncol, 110, 195-203. https://doi.org/10.1007/s11060-012-0970-9

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