https://doi.org/10.4081/monaldi.2022.2373

Can serum progranulin level be used as a prognostic biomarker in non-small cell lung cancer?

Vol. 93 No. 3 (2023)
Submitted: July 10, 2022
Accepted: November 8, 2022
Published: November 14, 2022
Progranulin, cancer, prognostic factor, biomarker
Abstract Views: 764
PDF: 134
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Authors

Nevin Taci Hoca
nevintacihoca@yahoo.com
https://orcid.org/0000-0002-6803-4181
Department of Pulmonology, Gazi University, Ankara, Turkey.
Ebru Ünsal
https://orcid.org/0000-0002-1879-7922
Department of Pulmonology, Yıldırım Beyazıt University, Ankara, Turkey.
Koza Murat
Department of Biochemistry, Saglik Bilimleri University, Ataturk Sanatoryum Education and Research Hospital, Ankara, Turkey.
Arzu Ertürk
https://orcid.org/0000-0002-8139-6750
Department of Pulmonology, Ahi Evran University, Kırsehir, Turkey.
Nermin Çapan
Department of Pulmonology, Saglik Bilimleri University, Ataturk Sanatoryum Education and Research Hospital, Ankara, Turkey.

Progranulin has been considered to be a poor prognostic biomarker for some types of malignancies. However, the clinical significance of serum progranulin level and the prognostic value are still not explored in advanced stages of lung cancer.  The current study investigates the prognostic significance of progranulin serum levels in advanced-stage non-small cell lung cancer (NSCLC) patients. This study involved 94 subjects (70 advanced-stage NSCLC patients and 24 healthy controls). Serum progranulin level was measured by enzyme-linked immunosorbent assay (ELISA) and was correlated with patient outcome. The association between circulating progranulin level and clinicopathological parameters was detected. Serum progranulin cut-off level predicting six-month survival was determined. Serum progranulin level was found significantly elevated in NSCLC patients than in the control group (p<0.001). We did not determine a significant difference between stage IIIB and stage IV NSCLC patients for serum progranulin levels (p=0.166). When we evaluated the laboratory parameters, only serum LDH level was found significantly correlated with serum progranulin level (p=0.043), also bone and liver metastasis showed a significant correlation with progranulin level (p=0.008 and p = 0.024, respectively). The cut-off level of serum progranulin in predicting six months of survival was determined as 16.03 ng/ml (AUC = 0.973, 95%Cl: 0.903-0.997, p<0.001) with 97.06% sensitivity and 88.89% specificity. Overall survival was determined shorter in patients with progranulin level ≥16 ng/ml than those with <16 ng/ml (p<0.001). Also, in the multivariate analysis using the Cox regression model serum progranulin level was found as an independent prognostic factor for NSCLC (p=0.001). Serum progranulin level may be a useful biomarker for predicting poor survival in advanced-stage NSCLC patients.

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Google Scholar
Europe PMC
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA: Cancer J Clin 2020;70:7-30. DOI: https://doi.org/10.3322/caac.21590
Woodard GA, Jones KD, Jablons DM. Lung cancer staging and prognosis. Cancer Treat Res 2016;170:47-75. DOI: https://doi.org/10.1007/978-3-319-40389-2_3
Travis WD, Brambilla E, Nicholson AG, et al. The 2015 World Health Organization classification of lung tumors: Impact of genetic, clinical and radiologic advances since the 2004 classification. J Thorac Oncol 2015;10:1243-60. DOI: https://doi.org/10.1097/JTO.0000000000000630
Puderecki M, Szumiło J, Marzec-Kotarska B. Novel prognostic molecular markers in lung cancer. Oncol Lett 2020;20:9-18. DOI: https://doi.org/10.3892/ol.2020.11541
Salgia R. Prognostic significance of angiogenesis and angiogenic growth factors in NSCLC. Cancer 2011;117:3889-99. DOI: https://doi.org/10.1002/cncr.25935
Arechavaleta-Velasco F, Perez-Juarez CE, Gerton GL, Diaz-Cueto L. Progranulin and its biological effects in cancer. Med Oncol 2017;34:194. DOI: https://doi.org/10.1007/s12032-017-1054-7
Ong CHP, Bateman A. Progranulin (granulin-epithelin precursor, PC-cell derived growth factor, acrogranin) in proliferation and tumorigenesis. Histol Histopathol 2003;18:1275-88.
Serrero G. Potential of theranostic target mining in the development of novel diagnostic and therapeutic products in oncology: Progranulin/GP88 as a therapeutic and diagnostic target for breast and lung cancers. Rinsho Byori 2016;64:1296-309.
Berger K, Rhost S, Rafnsdóttir S, et al. Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer. BMC Cancer 2021;21:185. DOI: https://doi.org/10.1186/s12885-021-07854-0
Purrahman D, Mahmoudian-Sani MR, Saki N, et al. Involvement of progranulin (PGRN) in the pathogenesis and prognosis of breast cancer. Cytokine 2022;151:155803. DOI: https://doi.org/10.1016/j.cyto.2022.155803
Voshtani R, Song M, Wang H, et al. Progranulin promotes melanoma progression by inhibiting natural killer cell recruitment to the tumor microenvironment. Cancer Lett 2019;465:24-35. DOI: https://doi.org/10.1016/j.canlet.2019.08.018
Tanimoto R, Lu KG, Xu SQ, et al. Mechanisms of progranulin action and regulation in genitourinary cancers. Front Endocrinol (Lausanne) 2016;7:100. DOI: https://doi.org/10.3389/fendo.2016.00100
Abella V, Pino J, Scotece M, et al. Progranulin as a biomarker and potential therapeutic agent. Drug Discov Today 2017;22:1557-64. DOI: https://doi.org/10.1016/j.drudis.2017.06.006
Yamamoto Y, Goto N, Takemura M, et al. Association between increased serum GP88 (progranulin) concentrations and prognosis in patients with malignant lymphomas. Clin Chim Acta 2017;473:139-46. DOI: https://doi.org/10.1016/j.cca.2017.07.024
Edelman MJ, Feliciano J, Yue B, et al. GP88 (progranulin): a novel tissue and circulating biomarker for non-small cell lung carcinoma. Hum Pathol 2014;45:1893-9. DOI: https://doi.org/10.1016/j.humpath.2014.05.011
Greither T, Fischer K, Theil G, et al. Expression of GP88 (progranulin) in serum of prostate cancer patients is associated with Gleason scores and overall survival. Cancer Manag Res 2018;10:4173-80. DOI: https://doi.org/10.2147/CMAR.S172069
Carlson AM, Maurer MJ, Goergen KM, et al. Utility of progranulin and serum leukocyte protease inhibitor as diagnostic and prognostic biomarkers in ovarian cancer. Cancer Epidemiol Biomarkers Prev 2013;22:1730-5. DOI: https://doi.org/10.1158/1055-9965.EPI-12-1368
Cerezo LA, Kuklová M, Hulejová H, et al. Progranulin is associated with disease activity in patients with rheumatoid arthritis. Mediators Inflamm 2015;2015:740357. DOI: https://doi.org/10.1155/2015/740357
Tanaka A, Tsukamoto H, Mitoma H, et al. Serum progranulin levels are elevated in dermatomyositis patients with acute interstitial lung disease, predicting prognosis. Arthritis Res Ther 2015;17:27. DOI: https://doi.org/10.1186/s13075-015-0547-z
Tanaka Y, Takahashi T, Tamori Y. Circulating progranulin level is associated with visceral fat and elevated liver enzymes: significance of serum progranulin as a useful marker for liver dysfunction. Endocr J 2014;61:1191-6. DOI: https://doi.org/10.1507/endocrj.EJ14-0210
Naumnik W, Panek B, Ossolińska M, Naumnik B. B Cell-attracting chemokine-1 and progranulin in bronchoalveolar lavage fluid of patients with advanced non-small-cell lung cancer: new prognostic factors. Adv Exp Med Biol 2019;1150:11-6. DOI: https://doi.org/10.1007/5584_2018_285
Qian L, Lin L, Du Y, et al. MicroRNA-588 suppresses tumor cell migration and invasion by targeting GRN in lung squamous cell carcinoma. Mol Med Rep 2016;14:3021-8. DOI: https://doi.org/10.3892/mmr.2016.5643
Zhou C, Huang Y, Wu J, et al. A narrative review of multiple mechanisms of progranulin in cancer: a potential target for anti-cancer therapy. Transl Cancer Res 2021;10:4207-16. DOI: https://doi.org/10.21037/tcr-20-2972
Kim WG. Association of serum progranulin levels with progression of papillary thyroid cancer. Endocrinol Metab (Seoul) 2020; 35:288-9. DOI: https://doi.org/10.3803/EnM.2020.35.2.288
Neill T, Buraschi S, Goyal A, et al. EphA2 is a functional receptor for the growth factor progranulin. J Cell Biol 2016;215:687-703. DOI: https://doi.org/10.1083/jcb.201603079

How to Cite

Taci Hoca, Nevin, Ebru Ünsal, Koza Murat, Arzu Ertürk, and Nermin Çapan. 2022. “Can Serum Progranulin Level Be Used As a Prognostic Biomarker in Non-Small Cell Lung Cancer?”. Monaldi Archives for Chest Disease 93 (3). https://doi.org/10.4081/monaldi.2022.2373.
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