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Nucleophosmin 1 overexpression correlates with 18F-FDG PET/CT metabolic parameters and improves diagnostic accuracy in patients with lung adenocarcinoma

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Abstract

Purpose

This study investigated the correlation of nucleophosmin 1 (NPM1) expression with 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computerised tomography scan (PET/CT)-related parameters and compared the diagnostic value of NPM1 with that of the positive biomarker TTF1 in lung adenocarcinoma patients.

Methods

Forty-six lung adenocarcinoma patients who underwent 18F-FDG PET/CT before pulmonary surgery were retrospectively analysed. Metabolic parameters including SUVmax, SUVmean, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) were calculated from 18F-FDG PET imaging data. The expression levels of NPM1 and TTF1 were assessed using The Cancer Genome Atlas (TCGA) database and immunohistochemistry of tumour tissues and adjacent normal lung tissues. We examined the association between the frequency of NPM1 and TTF1 expression and the metabolic parameters.

Results

Lung adenocarcinoma samples expressed higher levels of NPM1 than adjacent normal lung epithelial tissues. NPM1 showed higher specificity and sensitivity for lung adenocarcinoma compared with TTF1 (p < 0.001). SUVmax, SUVmean and TLG correlated with NPM1 expression (p < 0.001). MTV was inversely correlated with TTF1 (p < 0.01). SUVmax was the primary predictor of NPM1 expression by lung adenocarcinoma (p < 0.01). A cutoff value for the SUVmax of 3.93 allowed 90.9% sensitivity and 84.6% specificity for predicting NPM1 overexpression in lung adenocarcinoma.

Conclusion

NPM1 overexpression correlated with 18F-FDG PET/CT metabolic parameters and improved diagnostic accuracy in lung adenocarcinoma. SUVmax on 18F-FDG PET/CT may estimate NPM1 expression for targeted therapy of lung adenocarcinoma.

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References

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin. 2019;69:7–34.

    Article  PubMed  Google Scholar 

  2. 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 Cancer J Clin. 2018;68:394–424.

    Article  PubMed  Google Scholar 

  3. Kadara H, Kabbout M, Wistuba II. Pulmonary adenocarcinoma: a renewed entity in 2011. Respirology. 2012;17:50–65.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Hirsch FR, Scagliotti GV, Mulshine JL, Kwon R, Jr WJC, Wu Y, et al. Lung cancer: current therapies and new targeted treatments. The Lancet 2017;389:299–311.

  5. Zarogoulidis K, Zarogoulidis P, Darwiche K, Boutsikou E, Machairiotis N, Tsakiridis K, et al. Treatment of non-small cell lung cancer (NSCLC). J THORAC DIS. 2013;Suppl 4:S389–96.

  6. Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, et al. Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 2019;69:363–85.

  7. Jadvar H, Alavi A, Gambhir SS. 18F-FDG uptake in lung, breast, and Colon cancers: molecular biology correlates and disease characterization. J Nucl Med. 2009;50:1820–7.

    Article  PubMed  Google Scholar 

  8. Lopci E, Toschi L, Grizzi F, Rahal D, Olivari L, Castino GF, et al. Correlation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery. Eur J Nucl Med Mol I. 2016;43:1954–61.

  9. Chung HW, Lee KY, Kim HJ, Kim WS, So Y. FDG PET/CT metabolic tumor volume and total lesion glycolysis predict prognosis in patients with advanced lung adenocarcinoma. J Cancer Res Clin. 2014;140:89–98.

    Article  CAS  Google Scholar 

  10. Pei Z, Zeng J, Song Y, Gao Y, Wu R, Chen Y, et al. In vivo imaging to monitor differentiation and therapeutic effects of transplanted mesenchymal stem cells in myocardial infarction. Sci Rep. 2017;7:6296.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Kawada K, Nakamoto Y, Kawada M, Hida K, Matsumoto T, Murakami T, et al. Relationship between 18F-fluorodeoxyglucose accumulation and KRAS/BRAF mutations in colorectal cancer. Clin Cancer Res. 2012;18:1696–703.

    Article  CAS  PubMed  Google Scholar 

  12. Lee P, Weerasuriya DK, Lavori PW, Quon A, Hara W, Maxim PG, et al. Metabolic tumor burden predicts for disease progression and death in lung cancer. International Journal of Radiation Oncology Biology Physics. 2007;69:328–33.

    Article  PubMed  Google Scholar 

  13. Liao S, Penney BC, Wroblewski K, Zhang H, Simon CA, Kampalath R, et al. Prognostic value of metabolic tumor burden on 18F-FDG PET in nonsurgical patients with non-small cell lung cancer. Eur J Nucl Med Mol I. 2012;39:27–38.

  14. Na KJ, Choi H. Tumor metabolic features identified by 18F-FDG PET correlate with gene networks of immune cell microenvironment in head and neck cancer. J Nucl Med. 2018;59:31–7.

    Article  CAS  PubMed  Google Scholar 

  15. Nair VS, Gevaert O, Davidzon G, Napel S, Graves EE, Hoang CD, et al. Prognostic PET 18F-FDG uptake imaging features are associated with major oncogenomic alterations in patients with resected non-small cell lung cancer. Cancer Res. 2012;72:3725–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Vesselle H, Salskov A, Turcotte E, Wiens L, Schmidt R, Jordan CD, et al. Relationship between non-small cell lung cancer FDG uptake at PET, tumor histology, and Ki-67 proliferation index. J Thorac Oncol. 2008;3:971–8.

    Article  PubMed  Google Scholar 

  17. Song J, Lee YN, Kim YS, Kim SG, Jin SJ, Park JM, et al. Predictability of preoperative 18F-FDG PET for histopathological differentiation and early recurrence of primary malignant intrahepatic tumors. Nucl Med Commun. 2015;36:319–27.

    Article  CAS  PubMed  Google Scholar 

  18. Kaira K, Serizawa M, Koh Y, Takahashi T, Yamaguchi A, Hanaoka H, et al. Biological significance of 18F-FDG uptake on PET in patients with non-small-cell lung cancer. Lung Cancer. 2014;83:197–204.

    Article  PubMed  Google Scholar 

  19. Zegers CML, van Elmpt W, Reymen B, Even AJG, Troost EGC, Ollers MC, et al. In vivo quantification of hypoxic and metabolic status of NSCLC tumors using [18F]HX4 and [18F]FDG-PET/CT imaging. Clin Cancer Res. 2014;20:6389–97.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Ichikawa T, Aokage K, Miyoshi T, Tane K, Suzuki K, Makinoshima H, et al. Correlation between maximum standardized uptake values on FDG-PET and microenvironmental factors in patients with clinical stage IA radiologic pure-solid lung adenocarcinoma. Lung Cancer. 2019;136:57–64.

    Article  PubMed  Google Scholar 

  21. Huellner MW, de Galiza BF, Husmann L, Pietsch CM, Made CE, Burger IA, et al. TNM staging of NSCLC: comparison of PET/MR and PET/CT. J Nucl Med. 2016;57:21–6.

    Article  CAS  PubMed  Google Scholar 

  22. Berghmans T, Paesmans M, Mascaux C, Martin B, Meert A, Haller A, et al. Thyroid transcription factor 1-a new prognostic factor in lung cancer: a meta-analysis. Ann Oncol. 2006;17:1673–6.

    Article  CAS  PubMed  Google Scholar 

  23. Elsamany SA, Al-Fayea TM, Alzahrani AS, Abozeed WN, Darwish W, Farooq MU, et al. Thyroid transcription factor-1 expression in advanced non- small cell lung cancer impact on survival outcome. Asian Pac J Cancer Prev. 2015;16:2987–91.

  24. Ooi H, Chen C, Hsiao Y, Huang W, Hsieh B. Influence of thyroid transcription factor-1 on fluorodeoxyglucose uptake and prognosis of non-small cell lung cancer. Anticancer Res. 2014;34:2467–75.

  25. Wang S, Qin J, Ye H, Wang K, Shi J, Ma Y, et al. Using a panel of multiple tumor-associated antigens to enhance autoantibody detection for immunodiagnosis of gastric cancer. Oncoimmunology. 2018;7:e1452582.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Tang J, Chen H, Wong C, Liu D, Li T, Wang X, et al. DEAD-box helicase 27 promotes colorectal cancer growth and metastasis and predicts poor survival in CRC patients. Oncogene. 2018;37:3006–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Senapati P, Dey S, Sudarshan D, Das S, Kumar M, Kaypee S, et al. Oncogene c-fos and mutant R175H p53 regulate expression of Nucleophosmin implicating cancer manifestation. FEBS J. 2018;285:3503–24.

    Article  CAS  PubMed  Google Scholar 

  28. He J, Xiang Z, Xiao J, Xiao H, Liu L. The poor chemotherapeutic efficacy in lung adenocarcinoma overexpressing c-Src and nucleophosmin/B23(NPM1). Chinese Journal of Cellular and Molecular Immunology. 2016;32:1378–81.

    PubMed  Google Scholar 

  29. Chandrashekar DS, Bashel B, Balasubramanya SAH, Creighton CJ, Ponce-Rodriguez I, Chakravarthi BVSK, et al. UALCAN: a portal for facilitating tumor subgroup gene expression and survival analyses. Neoplasia. 2017;19:649–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Győrffy B, Surowiak P, Budczies J, Lánczky A. Correction: online survival analysis software to assess the prognostic value of biomarkers using transcriptomic data in non-small-cell lung Cancer. PLoS One. 2014;9:e111842.

  31. Wang Y, Zhao N, Wu Z, Pan N, Shen X, Liu T, et al. New insight on the correlation of metabolic status on 18F-FDG PET/CT with immune marker expression in patients with non-small cell lung cancer. Eur J Nucl Med Mol I. 2020;47:1127–36.

  32. Nakajima R, Abe K, Kondo T, Tanabe K, Sakai S. Clinical role of early dynamic FDG-PET/CT for the evaluation of renal cell carcinoma. Eur Radiol. 2016;26:1852–62.

  33. Lemarignier C, Martineau A, Teixeira L, Vercellino L, Espié M, Merlet P, et al. Correlation between tumour characteristics, SUV measurements, metabolic tumour volume, TLG and textural features assessed with 18F-FDG PET in a large cohort of oestrogen receptor-positive breast cancer patients. Eur J Nucl Med Mol I. 2017;44:1145–54.

  34. Yildirim BA, Torun N, Guler OC, Onal C. Prognostic value of metabolic tumor volume and total lesion glycolysis in esophageal carcinoma patients treated with definitive chemoradiotherapy. Nucl Med Commun. 2018;39:553–63.

    Article  PubMed  Google Scholar 

  35. Liu F, Chao A, Lai C, Chou H, Yen T. Metabolic tumor volume by 18F-FDG PET/CT is prognostic for stage IVB endometrial carcinoma. Gynecol Oncol. 2012;125:566–71.

    Article  PubMed  Google Scholar 

  36. Toledano MN, Desbordes P, Banjar A, Gardin I, Vera P, Ruminy P, et al. Combination of baseline FDG PET/CT total metabolic tumour volume and gene expression profile have a robust predictive value in patients with diffuse large B-cell lymphoma. Eur J Nucl Med Mol I. 2018;45:680–8.

  37. Wang X, Xu Z, Ren X, Chen X, Wei J, Lin W, et al. Function of low ADARB1 expression in lung adenocarcinoma. PLoS One. 2019.

  38. Di Fiore PP. Playing both sides: nucleophosmin between tumor suppression and oncogenesis. J Cell Biol. 2008;182:7–09.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Kaowinn S, Kim J, Lee J, Shin DH, Kang C, Kim D, et al. Cancer upregulated gene 2 induces epithelial-mesenchymal transition of human lung cancer cells via TGF-β signaling. Oncotarget. 2017;8:5092–110.

    Article  PubMed  Google Scholar 

  40. Yoshimura K, Inoue Y, Mori K, Iwashita Y, Kahyo T, Kawase A, et al. Distinct prognostic roles and heterogeneity of TTF1 copy number and TTF1 protein expression in non-small cell lung cancer. Genes Chromosom Cancer. 2017;56:570–81.

    Article  CAS  PubMed  Google Scholar 

  41. Huang T, Lin KF, Lee C, Chang H, Lee S, Shieh Y. The role of thyroid transcription factor-1 and tumor differentiation in resected lung adenocarcinoma. Sci Rep. 2017;7:14222.

  42. Liu Y, Zhang F, Zhang X, Qi L, Yang L, Guo H, et al. Expression of nucleophosmin/NPM1 correlates with migration and invasiveness of colon cancer cells. J Biomed Sci. 2012;19:53.

    Article  PubMed  PubMed Central  Google Scholar 

  43. 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;18:838.

  44. Grisendi S, Mecucci C, Falini B, Pandolfi PP. Nucleophosmin and cancer. Nat Rev Cancer 2006;6:493–505.

  45. Bond GL, Hu W, Bond EE, Robins H, Lutzker SG, Arva NC, et al. A single nucleotide polymorphism in the MDM2 promoter attenuates the p53 tumor suppressor pathway and accelerates tumor formation in humans. CELL. 2004;5:591–602.

  46. Smith TAD, Sharma RI, Thompson AM, Paulin FEM. Tumor 18F-FDG incorporation is enhanced by attenuation of P53 function in breast cancer cells in vitro. The Journal of Nuclear Medicine. 2006;47:1525.

    CAS  PubMed  Google Scholar 

  47. Taylor MD, Smith PW, Brix WK, Wick MR, Theodosakis N, Swenson BR, et al. Fluorodeoxyglucose positron emission tomography and tumor marker expression in non–small cell lung cancer. J Thorac Cardiovasc Surg. 2009;137:43–8.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Libby Cone, MD, MA, from Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac) for editing a draft of this manuscript.

Funding

This study was funded by the Natural Science Foundation of Hubei Province (grant no.2018CFB433), Science and Technology Development Foundation of Shiyan City (grant no. 18Y20,19Y33), Innovative Research Program for Graduates of Hubei University of Medicine (grant no. YC2019032, YC2019039, YC2020012), Free-exploring Foundation of Hubei University of Medicine (grant no. FDFR201903) and the Key Discipline Project of Hubei University of Medicine.

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Author notes

  1. Lu-Meng Zhou and Ling-Ling Yuan contributed equally to this work.

Authors and Affiliations

  1. Department of Nuclear Medicine and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, 442000, Hubei, China

    Lu-Meng Zhou, Yan Gao, Xu-Sheng Liu & Zhi-Jun Pei

  2. Postgraduate Training Basement of Jinzhou Medical University, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China

    Lu-Meng Zhou, Jian-Wei Yang & Zhi-Jun Pei

  3. Department of Pathology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China

    Ling-Ling Yuan

  4. Department of Eye center, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, China

    Qin Dai

  5. Hubei Key Laboratory of WudangLocal Chinese Medicine Research, Shiyan, Hubei, China

    Zhi-Jun Pei

  6. Hubei Key Laboratory of Embryonic Stem Cell Research, Shiyan, Hubei, China

    Zhi-Jun Pei

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  1. Lu-Meng Zhou
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Zhou, LM., Yuan, LL., Gao, Y. et al. Nucleophosmin 1 overexpression correlates with 18F-FDG PET/CT metabolic parameters and improves diagnostic accuracy in patients with lung adenocarcinoma. Eur J Nucl Med Mol Imaging 48, 904–912 (2021). https://doi.org/10.1007/s00259-020-05005-4

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