{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T17:09:47Z","timestamp":1771520987186,"version":"3.50.1"},"reference-count":28,"publisher":"Walter de Gruyter GmbH","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_cclm-2025-0867_abs_001\">\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Calcitonin (CT) is the established biomarker for medullary thyroid carcinoma (MTC), but its measurement is hampered by analytical limitations. Procalcitonin (PCT) and pro-gastrin-releasing peptide (ProGRP) have been proposed as alternative or complementary markers, yet the diagnostic value of ProGRP remains uncertain. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of ProGRP for MTC and compare its performance with\u00a0CT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-0867_abs_002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study followed PRISMA-DTA and SEDATE guidelines. PubMed, Embase, Cochrane Library, and Open Grey were searched through June 2025 without language or date restrictions. Eligible studies assessed serum ProGRP for diagnosis or follow-up of MTC and reported or allowed reconstruction of 2\u00a0\u00d7\u00a02 contingency data. Two reviewers independently screened, extracted data, and assessed study quality using QUADAS-2. A Bayesian bivariate random-effects meta-analysis estimated pooled sensitivity, specificity, likelihood ratios, and diagnostic odds ratios. Comparative analyses were performed for ProGRP studies also reporting\u00a0CT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-0867_abs_003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Eight studies (n=4,080) were included; four reported both ProGRP and CT (n=1,064). ProGRP showed pooled sensitivity of 74\u202f% and specificity of 95\u202f% (AUC 0.82), while CT achieved 94\u202f% sensitivity and 91\u202f% specificity (AUC 0.89). Subgroup analyses confirmed consistent ProGRP performance across diagnostic and follow-up settings. No publication bias was observed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_cclm-2025-0867_abs_004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>ProGRP demonstrates high specificity but lower sensitivity than CT for MTC diagnosis and surveillance. Although not a replacement for CT, ProGRP may serve as a valuable complementary biomarker, particularly in inconclusive cases. Harmonization of assays and prospective validation are required to define universal thresholds and integrate ProGRP into multimarker diagnostic algorithms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1515\/cclm-2025-0867","type":"journal-article","created":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T09:20:22Z","timestamp":1762507222000},"page":"732-740","source":"Crossref","is-referenced-by-count":0,"title":["Pro-gastrin releasing peptide as a tumor marker of medullary thyroid carcinoma: a comparative bivariate meta-analysis"],"prefix":"10.1515","volume":"64","author":[{"given":"Petra Petranovi\u0107","family":"Ov\u010dari\u010dek","sequence":"first","affiliation":[{"name":"Department of Oncology and Nuclear Medicine , University Hospital Center Sestre Milosrdnice , Zagreb , Croatia"},{"name":"School of Medicine, University of Zagreb , Zagreb , Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"D\u2019Aurizio","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine , Laboratory for Clinical Pathology, University Hospital of Udine , Udine , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Campenn\u00ec","sequence":"additional","affiliation":[{"name":"Nuclear Medicine Unit, Biomedical and Dental Sciences and Morpho-Functional Imaging , University of Messina , Messina , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frederik Anton","family":"Verburg","sequence":"additional","affiliation":[{"name":"Radiology and Nuclear Medicine , Erasmus Medical Center , Rotterdam , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0230-0974","authenticated-orcid":false,"given":"Luca","family":"Giovanella","sequence":"additional","affiliation":[{"name":"Nuclear Medicine and Thyroid Center, Gruppo Ospedaliero Moncucco , Lugano , Switzerland"},{"name":"Nuclear Medicine and Thyroid Center, University Hospital of Zurich , Zurich , Switzerland"},{"name":"Department of Clinical Chemistry and Endocrinology , Medysin , Luzern , Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"2026021916200366473_j_cclm-2025-0867_ref_001","doi-asserted-by":"crossref","unstructured":"Wells, SAJ, Asa, SL, Dralle, H, Elisei, R, Evans, DB, Gagel, RF, et al.. Revised American Thyroid Association guidelines for the management of medullary thyroid carcinoma. Thyroid 2015;25:567\u2013610. https:\/\/doi.org\/10.1089\/thy.2014.0335.","DOI":"10.1089\/thy.2014.0335"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_002","doi-asserted-by":"crossref","unstructured":"Bae, YJ, Schaab, M, Kratzsch, J. Calcitonin as biomarker for the medullary thyroid carcinoma. Recent Results Cancer Res 2015;204:117\u201337. https:\/\/doi.org\/10.1007\/978-3-319-22542-5_5","DOI":"10.1007\/978-3-319-22542-5_5"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_003","doi-asserted-by":"crossref","unstructured":"La Salvia, A, Fanciulli, G. Progastrin-releasing peptide as a diagnostic biomarker of pulmonary and non-pulmonary neuroendocrine neoplasms. Endocr Res 2025;49:243\u201350. https:\/\/doi.org\/10.1080\/07435800.2024.2365895.","DOI":"10.1080\/07435800.2024.2365895"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_004","doi-asserted-by":"crossref","unstructured":"Giovanella, L, Garo, ML, Ceriani, L, Paone, G, Campenni\u2019, A, D\u2019Aurizio, F. Procalcitonin as an alternative tumor marker of medullary thyroid carcinoma. J\u00a0Clin Endocrinol Metab 2021;106:3634\u201343. https:\/\/doi.org\/10.1210\/clinem\/dgab564.","DOI":"10.1210\/clinem\/dgab564"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_005","doi-asserted-by":"crossref","unstructured":"Clausi, C, Censi, S, Zanin, E, Messina, G, Piva, I, Basso, D, et al.. Combining procalcitonin and calcitonin for the diagnosis of medullary thyroid cancer: a two-step approach. Clin Endocrinol 2025. https:\/\/doi.org\/10.1111\/cen.15287.","DOI":"10.1111\/cen.15287"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_006","doi-asserted-by":"crossref","unstructured":"Parra-Robert, M, Orois, A, Aug\u00e9, JM, Halperin, I, Filella, X, Molina, R. Utility of proGRP as a tumor marker in the medullary thyroid carcinoma. Clin Chem Lab Med 2017;55:441\u20136. https:\/\/doi.org\/10.1515\/cclm-2016-0572.","DOI":"10.1515\/cclm-2016-0572"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_007","doi-asserted-by":"crossref","unstructured":"Fernandez, RM, Fern\u00e1ndez, E, Hurtado, H, Gallegos, Y, Mart\u00ednez, I, Aug\u00e9, JM. Pro-GRP in medullary thyroid cancer. Correlation with calcitonin and utility of them in the follow-up of the disease. Clin Chim Acta 2019;493:T123. https:\/\/doi.org\/10.1016\/j.cca.2019.03.306.","DOI":"10.1016\/j.cca.2019.03.306"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_008","doi-asserted-by":"crossref","unstructured":"Korse, CM, Holdenrieder, S, Zhi, XY, Zhang, X, Qiu, L, Geistanger, A, et al.. Multicenter evaluation of a new progastrin-releasing peptide (ProGRP) immunoassay across Europe and China. Clin Chim Acta 2015;438:388\u201395. https:\/\/doi.org\/10.1016\/j.cca.2014.09.015.","DOI":"10.1016\/j.cca.2014.09.015"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_009","doi-asserted-by":"crossref","unstructured":"Yoshimura, T, Yoshimura, T, Fujita, K, Kinukawa, H, Matsuoka, Y, Patil, RD, et al.. Development and analytical performance evaluation of an automated chemiluminescent immunoassay for pro-gastrin releasing peptide (ProGRP). Clin Chem Lab Med 2009;47:1557\u201363. https:\/\/doi.org\/10.1515\/cclm.2009.333.","DOI":"10.1515\/CCLM.2009.333"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_010","doi-asserted-by":"crossref","unstructured":"Sotiriadis, A, Papatheodorou, SI, Martins, WP. Synthesizing evidence from diagnostic accuracy TEsts: the SEDATE guideline. Ultrasound Obstet Gynecol 2016;47:386\u201395. https:\/\/doi.org\/10.1002\/uog.15762.","DOI":"10.1002\/uog.15762"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_011","doi-asserted-by":"crossref","unstructured":"Moher, D, Liberati, A, Tetzlaff, J, Altman, DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med 2009;6:e1000097. https:\/\/doi.org\/10.1371\/journal.pmed.1000097.","DOI":"10.1371\/journal.pmed.1000097"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_012","doi-asserted-by":"crossref","unstructured":"Kim, KW, Lee, J, Choi, SH, Huh, J, Park, SH. Systematic review and meta-analysis of studies evaluating diagnostic test accuracy: a practical review for clinical researchers-part I. General guidance and tips. Korean J Radiol 2015;16:1175\u201387. https:\/\/doi.org\/10.3348\/kjr.2015.16.6.1175.","DOI":"10.3348\/kjr.2015.16.6.1175"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_013","doi-asserted-by":"crossref","unstructured":"Reitsma, JB, Glas, AS, Rutjes, AWS, Scholten, RJPM, Bossuyt, PM, Zwinderman, AH. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J\u00a0Clin Epidemiol 2005;58:982\u201390. https:\/\/doi.org\/10.1016\/j.jclinepi.2005.02.022.","DOI":"10.1016\/j.jclinepi.2005.02.022"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_014","doi-asserted-by":"crossref","unstructured":"Rutter, CM, Gatsonis, CA. A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations. Stat Med 2001;20:2865\u201384. https:\/\/doi.org\/10.1002\/sim.942.","DOI":"10.1002\/sim.942"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_015","unstructured":"Macaskill, P, Gatsonis, C, Deeks, J, Harbord, R, Takwoingi, Y. Chapter 10: Analysing and presenting results. In: Deeks, JJ, Bossuyt, PM, Leeflang, MM, Takwoingi, Y, editors. Cochrane handbook for systematic reviews of diagnostic test accuracy, 1st ed. Chichester, UK: John Wiley & Sons; 2023. http:\/\/srdta.cochrane.org\/ [Accessed 1 Oct 2015]."},{"key":"2026021916200366473_j_cclm-2025-0867_ref_016","doi-asserted-by":"crossref","unstructured":"Deeks, JJ, Macaskill, P, Irwig, L. The performance of tests of publication bias and other sample size effects in systematic reviews of diagnostic test accuracy was assessed. J\u00a0Clin Epidemiol 2005;58:882\u201393. https:\/\/doi.org\/10.1016\/j.jclinepi.2005.01.016.","DOI":"10.1016\/j.jclinepi.2005.01.016"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_017","unstructured":"Han, XD, Lu, RQ, Hu, HY, Guo, L. Application of serum markers in medullary thyroid carcinoma. Zhonghua Yu Fang Yi Xue Za Zhi (Chin J Prev Med). 2021;55:1468\u201374. https:\/\/doi.org\/10.3760\/cma.j.cn112150-20210308-00229."},{"key":"2026021916200366473_j_cclm-2025-0867_ref_018","doi-asserted-by":"crossref","unstructured":"Miao, Q, Lv, X, Luo, L, Zhang, J, Cai, B. Exploring the application value of pro-gastrin-releasing peptide in the clinical diagnosis and surgical treatment of medullary thyroid carcinoma. Cancer Med 2023;12:19576\u201382. https:\/\/doi.org\/10.1002\/cam4.6572.","DOI":"10.1002\/cam4.6572"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_019","doi-asserted-by":"crossref","unstructured":"Liang, X, Zhu, J, Cai, M, Dai, Z, Fang, L, Chen, H, et al.. ProGRP as a novel biomarker for the differential diagnosis of medullary thyroid carcinoma in patients with thyroid nodules. Endocr Pract 2020;26:514\u201322. https:\/\/doi.org\/10.4158\/ep-2019-0396.","DOI":"10.4158\/EP-2019-0396"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_020","doi-asserted-by":"crossref","unstructured":"Giovanella, L, Fontana, M, Keller, F, Campenni, A, Ceriani, L, Paone, G. Circulating pro-gastrin releasing peptide (ProGRP) in patients with medullary thyroid carcinoma. Clin Chem Lab Med 2021;16:1569\u201373. https:\/\/doi.org\/10.1515\/cclm-2021-0361.","DOI":"10.1515\/cclm-2021-0361"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_021","doi-asserted-by":"crossref","unstructured":"Martins Fernandes, A, Batista, M, Augusto Silva, L, Elvas, R, Couto, J, Martins, RG, et al.. The role of procalcitonin and ProGRP in the follow-up of medullary thyroid carcinoma. Endocr Abstr 2025; 110:EP1429. https:\/\/doi.org\/10.1530\/endoabs.110.ep1429.","DOI":"10.1530\/endoabs.110.EP1429"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_022","doi-asserted-by":"crossref","unstructured":"Schonebaum, L, Visser, WE, van den Berg, S, Peeters, R. Pro-gastrin-releasing peptide as an additional screening marker in the diagnostic work up for medullary thyroid carcinoma. Endocr Abstr 2023;92:PS2-17-04.","DOI":"10.1530\/endoabs.92.PS2-17-04"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_023","doi-asserted-by":"crossref","unstructured":"Schonebaum, LE, van den Berg, SAA, van Balkum, M, Visser, WE, Giovanella, L, Peeters, RP. Progastrin-releasing peptide and procalcitonin as additional markers in the diagnostic workup for medullary thyroid carcinoma. Thyroid 2025;35:1030\u201338. https:\/\/doi.org\/10.1089\/thy.2024.0293.","DOI":"10.1089\/thy.2024.0293"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_024","doi-asserted-by":"crossref","unstructured":"Yoshimura, T, Fujita, K, Kawakami, S, Takeda, K, Chan, S, Beligere, G, et al.. Stability of pro-gastrin-releasing peptide in serum versus plasma. Tumor Biol 2008;29:224\u201330. https:\/\/doi.org\/10.1159\/000152940.","DOI":"10.1159\/000152940"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_025","doi-asserted-by":"crossref","unstructured":"Nisman, B, Nechushtan, H, Biran, H, Peled, N, Gantz-Sorotsky, H, Doviner, V, et al.. New ARCHITECT plasma pro-gastrin-releasing peptide assay for diagnosing and monitoring small-cell lung cancer. Br J Cancer 2016;114:469\u201376. https:\/\/doi.org\/10.1038\/bjc.2016.7.","DOI":"10.1038\/bjc.2016.7"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_026","doi-asserted-by":"crossref","unstructured":"Kim, HR, Oh, I-J, Shin, M-G, Park, J-S, Choi, H-J, Ban, H-J, et al.. Plasma proGRP concentration is sensitive and specific for discriminating small cell lung cancer from nonmalignant conditions or non-small cell lung cancer. J\u00a0Korean Med Sci 2011;26:625\u201330. https:\/\/doi.org\/10.3346\/jkms.2011.26.5.625.","DOI":"10.3346\/jkms.2011.26.5.625"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_027","doi-asserted-by":"crossref","unstructured":"Garo, ML, Campenn\u00ec, A, Petranovic-Ovcaricek, P, D\u2019Aurizio, F, Giovanella, L. Evolution of thyroid cancer biomarkers: from laboratory test to patients\u2019 clinical management. Clin Chem Lab Med 2022;61:935\u201345. https:\/\/doi.org\/10.1515\/cclm-2022-1087.","DOI":"10.1515\/cclm-2022-1087"},{"key":"2026021916200366473_j_cclm-2025-0867_ref_028","doi-asserted-by":"crossref","unstructured":"Giovanella, L, Fontana, M, Keller, F, Verburg, FA, Ceriani, L. Clinical performance of calcitonin and procalcitonin Elecsys\u00ae immunoassays in patients with medullary thyroid carcinoma. Clin Chem Lab Med 2021;59:1847\u201355, https:\/\/doi.org\/10.1515\/cclm-2020-1424.","DOI":"10.1515\/cclm-2020-1424"}],"container-title":["Clinical Chemistry and Laboratory Medicine (CCLM)"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/cclm-2025-0867\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/cclm-2025-0867\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T16:21:48Z","timestamp":1771518108000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.degruyterbrill.com\/document\/doi\/10.1515\/cclm-2025-0867\/html"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,10]]},"references-count":28,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,9,29]]},"published-print":{"date-parts":[[2026,2,24]]}},"alternative-id":["10.1515\/cclm-2025-0867"],"URL":"https:\/\/doi.org\/10.1515\/cclm-2025-0867","relation":{},"ISSN":["1434-6621","1437-4331"],"issn-type":[{"value":"1434-6621","type":"print"},{"value":"1437-4331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,10]]}}}