Aim: Lung cancer is the leading cause of mortality from cancer across the world. In this study, the use of serum nucleolin (NCL) and nucleophosmin (NPM1) levels as a marker in the diagnosis, prognosis and treatment response evaluation in lung cancer was investigated. Materials and Method: NCL and NPM1 levels of serum samples taken before chemotherapy and after 3-4 courses of chemotherapy from the control group and the patients diagnosed with lung cancer were studied using ELISA method. Results: Serum NCL and NPM1 levels of the patients were higher than of the controls (p = 0.085 for NCL, p = 0.000 for NPM1). NCL and NPM1 levels by histopathologic type were significantly higher in adenocarcinoma than in squamous cell carcinoma (p < 0.05 for each). In view of the treatment responses to chemotherapeutic agents, there was a statistically insignificant difference between the values before and after chemotherapy (p > 0.05 for each). Conclusion: High serum NCL and NPM1 levels were found to correlate with poor prognosis, poor treatment response and low survival rate. It can be concluded that serum NCL and NPM1 levels in lung cancer can be used as diagnostic and prognostic markers for the disease.
References
1.
Eröz R, Unluhizarci K, N C. Value of argyrophilic nucleolar organizing region protein determinations in nondiagnostic fine needle aspiration samples (due to insufficient cell groups) of thyroid nodules. Anal Quant Cytopathol Histpathol. 2013;35(4):226–31.
2.
Çolakoğlu S, Saritas A, Eroz R, Oktay M, Yaykasli K, Akoz A, et al. Is one-time carbon monoxide intoxication harmless? Evaluation by argyrophilic nucleolar-organizing regions staining method. Human & Experimental Toxicology. 2015;34(1):24–31.
3.
Damar İH, Eroz R. Argyrophilic Nucleolar Organizer Regions as New Biomarkers in ST-Elevation Myocardial Infarction. Journal of Cardiovascular Development and Disease. 9(2):58.
4.
Turan Sönmez F, Eröz R. The role of argyrophilic nucleolar organizing region-associated proteins in clinical exacerbation of chronic obstructive pulmonary disease. Journal of International Medical Research. 2018;46(12):4995–5003.
5.
NİSARİ M, ERÖZ R. Does capsaicin have therapeutic benefits in human colon adenocarcinoma? Selection of the most reliable dose via AgNOR. TURKISH JOURNAL OF MEDICAL SCIENCES. 50(4):1076–81.
6.
Nisari M, Yilmaz S, Eroz R, Ertekin T, Bircan D, Ulger H. The detection of curcumins’ antitumoral effects via argyrophilic nucleolar organizing region-associated protein synthesis in mice with ehrlich’s ascitic carcinoma. Bratislava Medical Journal. 2017;118(01):61–5.
7.
Ertekin T, Bozkurt O, Eroz R, Nisari M, Bircan D, Nisari M, et al. May argyrophilic nucleolar organizing region-associated protein synthesis be used for selecting the most reliable dose of drugs such as rhamnetin in cancer treatments? Bratislava Medical Journal. 2017;117(11):653–8.
8.
Argyrophilic nucleolar organizing regions associated proteins in oncocytology.
9.
Eroz R, Cucer N, Karaca Z, Unluhizarci K, Ozturk F. The Evaluation of Argyrophilic Nucleolar Organizing Region Proteins in Fine-Needle Aspiration Samples of Thyroid. Endocrine Pathology. 2011;22(2):74–8.
10.
Oktay M, Eroz R, Oktay N, Erdem H, Başar F, Akyol L, et al. Argyrophilic nucleolar organizing region associated protein synthesis for cytologic discrimination of follicular thyroid lesions. Biotechnic & Histochemistry. 2015;90(3):179–83.
11.
Eroz R, Cucer N, Unluhizarci K, Ozturk F. Detection and comparison of cut‐off values for total AgNOR area/nuclear area and AgNOR number/nucleus in benign thyroid nodules and normal thyroid tissue. Cell Biology International. 2013;37(3):257–61.
12.
Saritas A, Gunes H, Colakoglu S, Eroz R, Akoz A, Oktay M, et al. Are there any effects of chronic carbon monoxide exposure on argyrophilic nucleolar-organizing region–associated protein synthesis in rat myocardium? Human & Experimental Toxicology. 2016;35(9):921–8.
13.
Tasdemir S, Eroz R, Cucer N, Oktay M, Türkeli M. Comparison of fine needle aspiration biopsy and paraffin embedded tissue sections for measuring AgNOR proteins. Biotechnic & Histochemistry. 2015;90(5):395–9.
14.
Nisari M, Eroz R, Nisari M, Ertekin T, Oktay M, Kavutcu M. Investigation of argyrophilic nucleolar organizing region. Bratislava Medical Journal. 2016;117(06):345–50.
15.
Eroz R, Yilmaz S, Cucer N. Argyrophilic nucleolar organizing region associated protein synthesis in hair root cells of humans at different developmental stages and sex. Biotechnic & Histochemistry. 2013;88(5):267–71.
16.
Eroz R, Tasdemir S, Dogan H. Is there any relationship between decreased AgNOR protein synthesis and human hair loss? Biotechnic & Histochemistry. 2012;87(8):494–8.
17.
Tasdemir S, Eroz R, Dogan H, Erdem HB, Sahin I, Kara M, et al. Association Between Human Hair Loss and the Expression Levels of Nucleolin, Nucleophosmin, andUBTFGenes. Genetic Testing and Molecular Biomarkers. 2016;20(4):197–202.
18.
Selvi B, Demirtas H, Eroz R, Imamoglu N. Reduction of the argyrophilic nucleolar organizing region associated protein synthesis with age in buccal epithelial cells of healthy individuals. Aging Clinical and Experimental Research. 2015;27(2):201–8.
19.
Eroz R, Okur M, A O. Does higher NORs expression affect the developmental stages of Down syndrome infants? Genet Couns. 2012;23(2):249–53.
20.
Imamoglu N, Eroz R, Canatan H, Demirtas H, Saatci Ç. Nuclear AgNOR protein enhancement in nucleoplasms of peripheral blood lymphocytes of babies/children with down syndrome. Microscopy Research and Technique. 2016;79(3):133–9.
21.
Kaya M, Eroz R, Kabakliogli M. Expression of nucleolin, nucleophosmin, upstream binding transcription factor genes and propolis in wound models. Journal of Wound Care. 2022;31(Sup10):S28–40.
22.
Huang F, Wu Y, Tan H, Guo T, Zhang K, Li D, et al. Phosphorylation of nucleolin is indispensable to its involvement in the proliferation and migration of non-small cell lung cancer cells. Oncology Reports.
23.
Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians. 2018;68(6):394–424.
24.
Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Curran WJ, Wu YL, et al. Lung cancer: current therapies and new targeted treatments. The Lancet. 2017;389(10066):299–311.
25.
Lee JH, Lee YS, Jeong SA, Khadka P, Roth J, Chung IK. Catalytically active telomerase holoenzyme is assembled in the dense fibrillar component of the nucleolus during S phase. Histochemistry and Cell Biology. 2014;141(2):137–52.
26.
Li N, Yuan K, Yan F, Huo Y, Zhu T, Liu X, et al. PinX1 is recruited to the mitotic chromosome periphery by Nucleolin and facilitates chromosome congression. Biochemical and Biophysical Research Communications. 2009;384(1):76–81.
27.
Grisendi S, Mecucci C, Falini B, Pandolfi PP. Nucleophosmin and cancer. Nature Reviews Cancer. 2006;6(7):493–505.
28.
Chen S, He H, Wang Y, Liu L, Liu Y, You H, et al. Poor prognosis of nucleophosmin overexpression in solid tumors: a meta-analysis. BMC Cancer. 2018;18(1).
29.
Goldstraw P, Chansky K, Crowley J, Rami-Porta R, Asamura H, Eberhardt WEE, et al. The IASLC Lung Cancer Staging Project: Proposals for Revision of the TNM Stage Groupings in the Forthcoming (Eighth) Edition of the TNM Classification for Lung Cancer. Journal of Thoracic Oncology. 2016;11(1):39–51.
30.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). European Journal of Cancer. 2009;45(2):228–47.
31.
Hsu TI, Lin SC, Lu PS, Chang WC, Hung CY, Yeh YM, et al. Erratum: MMP7-mediated cleavage of nucleolin at Asp255 induces MMP9 expression to promote tumor malignancy. Oncogene. 2017;36(6):875–6.
32.
Zhao H, Huang Y, Xue C, Chen Y, Hou X, Guo Y, et al. Prognostic Significance of the Combined Score of Endothelial Expression of Nucleolin and CD31 in Surgically Resected Non-Small Cell Lung Cancer. PLoS ONE. 8(1):e54674.
33.
Ferlay J, Colombet M, I S. Cancer statistics for the year 2020: An overview. Int J Cancer. 2021;
34.
Xu J yu, Lu S, Xu X ying, Hu S liu, Li B, Li W xin, et al. Prognostic significance of nuclear or cytoplasmic nucleolin expression in human non-small cell lung cancer and its relationship with DNA-PKcs. Tumor Biology. 2016;37(8):10349–56.
35.
Zhou Y, Shen J, Xia L, Wang Y. Estrogen mediated expression of nucleophosmin 1 in human endometrial carcinoma clinical stages through estrogen receptor-α signaling. Cancer Cell International. 2014;14(1).
36.
Sekhar KR, Benamar M, Venkateswaran A, Sasi S, Penthala NR, Crooks PA, et al. Targeting Nucleophosmin 1 Represents a Rational Strategy for Radiation Sensitization. International Journal of Radiation Oncology*Biology*Physics. 2014;89(5):1106–14.
37.
He J, Xiang Z, J X. The poor chemotherapeutic efficacy in lung adenocarcinoma overexpressing c-Src and nucleophosmin/B23(NPM1. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2016;32(10):1378–81.
38.
Zhou LM, Yuan LL, Gao Y, Liu XS, Dai Q, Yang JW, et al. Nucleophosmin 1 overexpression correlates with 18F-FDG PET/CT metabolic parameters and improves diagnostic accuracy in patients with lung adenocarcinoma. European Journal of Nuclear Medicine and Molecular Imaging. 2021;48(3):904–12.
39.
Karagun E, Eroz R. Argyrophilic nucleolar organizing regions in patients with Xeroderma Pigmentosum Group E. Experimental Dermatology. 2021;30(3):416–7.
40.
Kabaklıoğlu M, Eroz R, Kaya M. May Argyrophilic Nucleolar Organizer Regions Be Used as a Biomarker for the Detection of the Degree of Ischemic Damage Instead of Tunel in Testicular Torsion? Medicina. 57(11):1177.
41.
Yesildag K, Kokulu K, Mutlu H, Eroz R, Taha-Sert E, Saritas A. Argyrophilic nucleolar organizer regions as a promising biomarker for the detection of brain hypoxia levels caused by different doses of carbon monoxide poisoning. Gaceta Médica de México. 2023;157(6).
42.
Kandiş H, Afacan M, Eröz R, Colakoglu S, Bayramoglu A, Oktay M, et al. Can argyrophilic nucleolar organizing region-associated protein amount be used for the detection of cardiac damage? Human & Experimental Toxicology. 2016;35(3):323–31.
The statements, opinions and data contained in the journal are solely those of the individual authors and contributors and not of the publisher and the editor(s). We stay neutral with regard to jurisdictional claims in published maps and institutional affiliations.
