Skip to main content

Advertisement

SpringerLink
Log in

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

  • Research Article
  • Published:
Tumor Biology

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2012. CA Cancer J Clin. 2012;62:10–29.

    Article  PubMed  Google Scholar 

  2. Jemal A, Bray F, Center MM, et al. Global cancer statistics. CA Cancer J Clin. 2011;61:69–90.

    Article  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  7. Dores RM, Baron AJ. Evolution of POMC: origin, phylogeny, posttranslational processing, and the melanocortins. Ann N Y Acad Sci. 2011;1220:34–48.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  Google Scholar 

  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.

    Article  PubMed  Google Scholar 

  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.

    CAS  PubMed  PubMed Central  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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.

    Article  CAS  PubMed  Google Scholar 

  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. 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.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

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

Author information

Authors and Affiliations

  1. Department of Lung Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Huanhu West Road, Tianjin, 300060, China

    Ligang Hao, Xiaoliang Zhao, Bin Zhang, Chenguang Li & Changli Wang

  2. Key Laboratory of Cancer Prevention and Therapy, Tianjin, China

    Ligang Hao, Xiaoliang Zhao, Bin Zhang, Chenguang Li & Changli Wang

  3. Tianjin Lung Cancer Center, Tianjin, China

    Ligang Hao, Xiaoliang Zhao, Bin Zhang, Chenguang Li & Changli Wang

Authors
  1. Ligang Hao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaoliang Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bin Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Chenguang Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Changli Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Changli Wang.

Additional information

Ligang Hao and Xiaoliang Zhao contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hao, L., Zhao, X., Zhang, B. et al. Positive expression of pro-opiomelanocortin (POMC) is a novel independent poor prognostic marker in surgically resected non-small cell lung cancer. Tumor Biol. 36, 1811–1817 (2015). https://doi.org/10.1007/s13277-014-2784-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2784-1

Keywords

Search

Navigation