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Tumor Biology

, Volume 36, Issue 3, pp 1811–1817 | Cite as

Positive expression of pro-opiomelanocortin (POMC) is a novel independent poor prognostic marker in surgically resected non-small cell lung cancer

  • Ligang Hao
  • Xiaoliang Zhao
  • Bin Zhang
  • Chenguang Li
  • Changli Wang
Research Article

Abstract

This study aims to investigate the expression level of pro-opiomelanocortin (POMC) and its prognostic value in non-small cell lung cancer (NSCLC). Immunohistochemical staining was used to detect the expression level of POMC. Correlations between POMC expression and clinical and pathological characteristics were evaluated with the chi-square test, and the prognostic value was determined with the Kaplan–Meier method and COX proportional hazards model, α < 0.05. Of the samples, 48.0 % had positive POMC expression. POMC expression was significantly related to poorly differentiated tumors, N-stage, p-stage, postoperative failure pattern, expression of vimentin, and expression of E-cadherin (P < 0.05). Multivariate analysis revealed that POMC-positive expression was an independent risk factor for disease-free survival (hazard ratio (HR) 1.988, 95 % confidence interval (CI) 1.094–3.910, P = 0.024) and overall survival (HR 1.892, 95 % CI 1.726–3.709, P = 0.036). The addition of POMC protein expression to the prognostic model using pathological stage markedly improved the prognostic potential, and the area under the ROC increased from 0.691 to 0.775. Further study revealed that patients with POMC-negative expression can benefit more from a regimen of paclitaxel and carboplatin chemotherapy than a regimen of vinorelbine and carboplatin compared to patients with POMC-positive expression. We found that POMC-positive expression is a novel, independent poor prognostic marker in patients with NSCLC. Prospective studies are needed to validate the potential prognostic value of POMC in combination with the current staging system and in consideration of adjuvant chemotherapy.

Keywords

Pro-opiomelanocortin (POMCNon-small cell lung cancer (NSCLC) Prognosis 

Notes

Acknowledgments

This work was supported by the Tianjin Municipal Science and Technology Commission (12ZCDZSY15400, 12JCYBJC17800), National Natural Science Foundation of China (81302001 and 81470137), and China Postdoctoral Science Foundation (2014M550147).

Contributorship statement

LG H and XL Z performed the experiment and wrote the manuscript. B Z and CG L were responsible for the experimental design, collection of the tumor samples, and experiment data analysis. CL W was the guarantor of all the work and responsible for editing the manuscript.

Conflicts of interest

None

References

  1. 1.
    Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.CrossRefPubMedGoogle Scholar
  2. 2.
    Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.CrossRefPubMedGoogle Scholar
  3. 3.
    Groome PA, Bolejack V, Crowley JJ, et al. The IASLC Lung Cancer Staging Project: validation of the proposals for revision of the T, N, and M descriptors and consequent stage groupings in the forthcoming (seventh) edition of the TNM classification of malignant tumours. J Thorac Oncol. 2007;2:694–705.CrossRefPubMedGoogle Scholar
  4. 4.
    Al-Kattan K, Sepsas E, Fountain SW, Townsend ER. Disease recurrence after resection for stage I lung cancer. Eur J Cardiothorac Surg. 1997;12:380–4.CrossRefPubMedGoogle Scholar
  5. 5.
    Zhu CQ, Shih W, Ling CH, Tsao MS. Immunohistochemical markers of prognosis in non-small cell lung cancer: a review and proposal for a multiphase approach to marker evaluation. J Clin Pathol. 2006;59:790–800.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Raffin-Sanson ML, de Keyzer Y, Bertagna X. Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions. Eur J Endocrinol. 2003;149:79–90.CrossRefPubMedGoogle Scholar
  7. 7.
    Dores RM, Baron AJ. Evolution of POMC: origin, phylogeny, posttranslational processing, and the melanocortins. Ann N Y Acad Sci. 2011;1220:34–48.CrossRefPubMedGoogle Scholar
  8. 8.
    Tsai HE, Liu LF, Dusting GJ, et al. Pro-opiomelanocortin gene delivery suppresses the growth of established Lewis lung carcinoma through a melanocortin-1 receptor-independent pathway. J Gene Med. 2012;14:44–53.CrossRefPubMedGoogle Scholar
  9. 9.
    Fassnacht M, Hahner S, Hansen IA, et al. N-terminal proopiomelanocortin acts as a mitogen in adrenocortical tumor cells and decreases adrenal steroidogenesis. J Clin Endocrinol Metab. 2003;88:2171–9.CrossRefPubMedGoogle Scholar
  10. 10.
    Herraiz C, Journe F, Abdel-Malek Z, et al. Signaling from the human melanocortin 1 receptor to ERK1 and ERK2 mitogen-activated protein kinases involves transactivation of cKIT. Mol Endocrinol. 2011;25:138–56.CrossRefPubMedGoogle Scholar
  11. 11.
    Ahn HK, Jung M, Ha SY, et al. Clinical significance of Ki-67 and p53 expression in curatively resected non-small cell lung cancer. Tumour Biol. 2014;35:5735–40.CrossRefPubMedGoogle Scholar
  12. 12.
    Hiroshima K, Iyoda A, Shibuya K, et al. Prognostic significance of neuroendocrine differentiation in adenocarcinoma of the lung. Ann Thorac Surg. 2002;73:1732–5.CrossRefPubMedGoogle Scholar
  13. 13.
    Texier PL, de Keyzer Y, Lacave R, et al. Proopiomelanocortin gene expression in normal and tumoral human lung. J Clin Endocrinol Metab. 1991;73:414–20.CrossRefPubMedGoogle Scholar
  14. 14.
    Krajnik M, Schafer M, Sobanski P, et al. Local pulmonary opioid network in patients with lung cancer: a putative modulator of respiratory function. Pharmacol Rep. 2010;62:139–49.CrossRefPubMedGoogle Scholar
  15. 15.
    Stovold R, Meredith SL, Bryant JL, et al. Neuroendocrine and epithelial phenotypes in small-cell lung cancer: implications for metastasis and survival in patients. Br J Cancer. 2013;108:1704–11.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Pelte MF, Schwaller J, Cerrato C, Meier CA. Pro-opiomelanocortin expression in a metastatic breast carcinoma with ectopic ACTH secretion. Breast J. 2004;10:350–4.CrossRefPubMedGoogle Scholar
  17. 17.
    Noorlander I, Elte JW, Manintveld OC, et al. A case of recurrent non-small-cell lung carcinoma and paraneoplastic Cushing's syndrome. Lung Cancer. 2006;51:251–5.CrossRefPubMedGoogle Scholar
  18. 18.
    Tsai HE, Liu GS, Kung ML, et al. Downregulation of hepatoma-derived growth factor contributes to retarded lung metastasis via inhibition of epithelial-mesenchymal transition by systemic POMC gene delivery in melanoma. Mol Cancer Ther. 2013;12:1016–25.CrossRefPubMedGoogle Scholar
  19. 19.
    Sarkar DK, Zhang C, Murugan S, et al. Transplantation of beta-endorphin neurons into the hypothalamus promotes immune function and restricts the growth and metastasis of mammary carcinoma. Cancer Res. 2011;71:6282–91.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Morano MI, de Antueno RJ, Niedfeld G, Estivariz FE. Neuroendocrine alterations in nude mice with a human lung carcinoma producing pro-opiomelanocortin, corticotrophin-releasing hormone and arginine vasopressin. Clin Endocrinol (Oxf). 1990;32:349–62.CrossRefGoogle Scholar
  21. 21.
    Stovold R, Blackhall F, Meredith S, et al. Biomarkers for small cell lung cancer: neuroendocrine, epithelial and circulating tumour cells. Lung Cancer. 2012;76:263–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Xu ZH, Hang JB, Hu JA, Gao BL. RAF1-MEK1-ERK/AKT axis may confer NSCLC cell lines resistance to erlotinib. Int J Clin Exp Pathol. 2013;6:1493–504.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Wang ZL, Fan ZQ, Jiang HD, Qu JM. Selective Cox-2 inhibitor celecoxib induces epithelial-mesenchymal transition in human lung cancer cells via activating MEK-ERK signaling. Carcinogenesis. 2013;34:638–46.CrossRefPubMedGoogle Scholar
  24. 24.
    Soltermann A, Tischler V, Arbogast S, et al. Prognostic significance of epithelial-mesenchymal and mesenchymal-epithelial transition protein expression in non-small cell lung cancer. Clin Cancer Res. 2008;14:7430–7.CrossRefPubMedGoogle Scholar
  25. 25.
    Yoo SB, Kim YJ, Kim H, et al. Alteration of the E-cadherin/beta-catenin complex predicts poor response to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment. Ann Surg Oncol. 2013. doi: 10.1245/s10434-013-2970-1.Google Scholar
  26. 26.
    Nwogu CE, Yendamuri S, Tan W, et al. Lung cancer lymph node micrometastasis detection using real-time polymerase chain reaction: correlation with vascular endothelial growth factor expression. J Thorac Cardiovasc Surg. 2013;145:702–7. discussion 707-708.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Ligang Hao
    • 1
    • 2
    • 3
  • Xiaoliang Zhao
    • 1
    • 2
    • 3
  • Bin Zhang
    • 1
    • 2
    • 3
  • Chenguang Li
    • 1
    • 2
    • 3
  • Changli Wang
    • 1
    • 2
    • 3
  1. 1.Department of Lung CancerTianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for CancerTianjinChina
  2. 2.Key Laboratory of Cancer Prevention and TherapyTianjinChina
  3. 3.Tianjin Lung Cancer CenterTianjinChina

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