Endokrin Tümörlerde Protein Bazlı Biyobelirteçlerin Moleküler Analizi ve İn Siliko Yönetim Yaklaşımları

Deulkar P, Singam A, Jain A. A Comprehensive Review of the Role of Biomarkers in the Early Detection of Endocrine Disorders in Critical Illnesses. Cureus. 2024;31;16(5): e61409. doi: 10.7759/cureus.61409. PMID: 38947617; PMCID: PMC11214685.

Kędzierska M, Bańkosz M. Role of proteins in oncology: Advances in cancer diagnosis, prognosis, and targeted therapy—A narrative review. Journal of Clinical Medicine. MDPI. 2024;13(23):7131. doi:10.3390/jcm13237131

Kori M, Gov E, Arga KY, Sinha R. Biomarkers From Discovery to Clinical Application: In Silico Pre-Clinical Validation Approach in the Face of Lung Cancer. Biomarker Insights. SAGE Publications. 2024;3;19:11772719241287400. doi:10.1177/11772719241287400

Martins RS, Jesus TT, Cardoso L, Soares P, Vinagre J. Personalized medicine in medullary thyroid carcinoma: A broad review of emerging treatments. Journal of Personalized Medicine. 2023;13(7):1132. doi:10.3390/jpm13071132

Ramamoorthy B, Nilubol N. Multiple endocrine neoplasia type 1 syndrome pancreatic neuroendocrine tumor genotype/phenotype: Is there any advance on predicting or preventing? Surgical Oncology Clinics of North America. 2023;32(2):315–325. doi:10.1016/j.soc.2022.10.008

Colapietra F, Della Monica P, Di Napoli R, França Vieira e Silva F, Settembre G, Marino MM, Ballini A, Cantore S, Di Domenico M. Epigenetic modifications as novel biomarkers for diagnosis, prognosis, and therapeutic targeting in thyroid, pancreas, and lung neuroendocrine tumors. Journal of Clinical Medicine. 2025;14(8):2622. doi:10.3390/jcm14082622

Franchina M, Cavalcoli F, Falco O, La Milia M, Elvevi A, Massironi S. Biochemical markers for neuroendocrine tumors: Traditional circulating markers and recent development—A comprehensive review. Diagnostics. 2024;14(12):1289. doi:10.3390/diagnostics14121289

Raynor WY Kempf JS. Somatostatin Receptor PET Imaging of Physiologic and Benign Processes: Implications for Image Interpretation, Avoiding Pitfalls, and Clinical Applications. Supplement to Applied Radiology. 2024;(1):36-43.

Koffas A, Giakoustidis A, Papaefthymiou A, Bangeas P, Giakoustidis D, Papadopoulos VN, Toumpanakis C. Diagnostic work-up and advancement in the diagnosis of gastroenteropancreatic neuroendocrine neoplasms. Frontiers in Surgery. 2023;10:1064145. doi:10.3389/fsurg.2023.1064145

Uhlig R, Dum D, Gorbokon N, Menz A, Büscheck F, Luebke AM, Hube-Magg C, Hinsch A, Höflmayer D, Fraune C, Möller K, Bernreuther C, Lebok P, Weidemann S, Lennartz M, Jacobsen F, Clauditz TS, Sauter G, Wilczak W, Steurer S, Burandt E, Krech R, Krech T, Marx AH, Simon R, Minner S. Synaptophysin and chromogranin A expression analysis in human tumors. Molecular and Cellular Endocrinology. 2022;555:111726. doi:10.1016/j.mce.2022.111726

Tomita T. Significance of chromogranin A and synaptophysin in pancreatic neuroendocrine tumors. Biomolecules and Biomedicine. 2020;20(3):336–346. doi:10.17305/bjbms.2020.4632

Zhang N, Liu Q, Wang D, et al. Multifaceted roles of Galectins: from carbohydrate binding to targeted cancer therapy. Biomarker Research. 2025;13:49. doi:10.1186/s40364-025-00759-1

Tao Z, Xue R, Wei Z, Qin L, Bai R, Liu N, Wang J, Wang C. The assessment of Ki-67 for prognosis of gastroenteropancreatic neuroendocrine neoplasm patients: a systematic review and meta-analysis. Translational Cancer Research. 2023;12(8):1980–1991. doi:10.21037/tcr-23-248

Gattenlöhner S, Stühmer T, Leich E, Reinhard M, Etschmann B, Völker HU, Rosenwald A, Serfling E, Bargou RC, Ertl G, Einsele H, Müller-Hermelink HK. Specific detection of CD56 (NCAM) isoforms for the identification of aggressive malignant neoplasms with progressive development. The American Journal of Pathology. 2009;174(4):1160–1171. doi:10.2353/ajpath.2009.080647

Bahrami A, Gown A, Baird G, et al. Aberrant expression of epithelial and neuroendocrine markers in alveolar rhabdomyosarcoma: a potentially serious diagnostic pitfall. Modern Pathology. Nature Publishing Group. 2008;21(7):795–806. doi:10.1038/modpathol.2008.86

Arcolia V, Journe F, Renaud F, Leteurtre E, Gabius HJ, Remmelink M, Saussez S. Combination of galectin-3, CK19 and HBME-1 immunostaining improves the diagnosis of thyroid cancer. Oncology Letters. 2017 Oct;14(4):4183–4189. doi:10.3892/ol.2017.6719.

Peștean C, Pavel A, Piciu D. Clinical and paraclinical considerations regarding Ki-67's role in the management of differentiated thyroid carcinoma: a literature review. Medicina. 2024;60(5):769. doi:10.3390/medicina60050769.

Hellgren LS, Stenman A, Paulsson JO, Höög A, Larsson C, Zedenius J, Juhlin CC. Prognostic utility of the Ki-67 labeling index in follicular thyroid tumors: a 20-year experience from a tertiary thyroid center. Endocrine Pathology. 2022;33(2):231–242. doi:10.1007/s12022-022-09714-4.

Masui T, Yane K, Ota I, Kakudo K, Wakasa T, Koike S, Kinugawa H, Yasumatsu R, Kitahara T. Low Ki-67 labeling index is a clinically useful predictive factor for recurrence-free survival in patients with papillary thyroid carcinoma. Journal of Pathology and Translational Medicine. 2025;59(2):115–124. doi:10.4132/jptm.2024.11.08.

Prinzi A, Frasca F, Russo M, Pellegriti G, Piticchio T, Tumino D, Belfiore A, Malandrino P. Pre-operative calcitonin and CEA values may predict the extent of metastases to the lateral neck lymph nodes in patients with medullary thyroid cancer. Cancers. 2024;16(17):2979. doi:10.3390/cancers16172979.

Yoo JH, Leem DE, Kim BR, Kim TH, Kim SW, Chung JH. Medullary thyroid carcinoma detected by routine health screening had better clinical outcome and survival. Endocrinology and Metabolism. 2025;40(3):414–420.

Sipos JA, Aloi J, Gianoukakis A, Lee SL, Klopper JP, Kung JT, Lupo MA, Morgenstern D, Prat-Knoll C, Schuetzenmeister A, Goldner WS. Thyroglobulin cutoff values for detecting excellent response to therapy in patients with differentiated thyroid cancer. Journal of the Endocrine Society. 2023;7(9):bvad102. doi:10.1210/jendso/bvad102.

Sule R, Rivera G, Gomes AV. Western blotting (immunoblotting): history, theory, uses, protocol and problems. BioTechniques. 2023;75(3):99–114. doi:10.2144/btn-2022-0034

Aydin S, Emre E, Ugur K, et al. An overview of ELISA: a review and update on best laboratory practices for quantifying peptides and proteins in biological fluids. Journal of International Medical Research. SAGE Publications Ltd. 2025;53(2): doi:10.1177/03000605251315913

Abouelfadl DM, Shabana ME, Soliman ASA, Yassen NN. Evaluation of the immunohistochemical expression of Nrf2, galectin-3, and CK19 in papillary thyroid carcinoma and its mimics. Egyptian Journal of Pathology. Medknow Publications. 2024;44(2):150–158. doi:10.4103/egjp.egjp_34_24

Wenk D, Zuo C, Kislinger T, et al. Recent developments in mass-spectrometry-based targeted proteomics of clinical cancer biomarkers. Clinical Proteomics. BioMed Central. 2024;21:6. doi:10.1186/s12014-024-09452-1

Bessaad M, Habel A, Hadj Ahmed M, Xu W, Stayoussef M, Bouaziz H, Hachiche M, Mezlini A, Larbi A, Yaacoubi-Loueslati B. Assessing serum cytokine profiles in inflammatory breast cancer patients using Luminex® technology. Cytokine. Elsevier. 2023;172:156409. doi:10.1016/j.cyto.2023.156409.

Coll-de la Rubia E, Martinez-Garcia E, Dittmar G, Nazarov PV, Bebia V, Cabrera S, Gil-Moreno A, Colás E. In silico approach for validating and unveiling new applications for prognostic biomarkers of endometrial cancer. Cancers (Basel). MDPI. 2021;13(20):5052. doi:10.3390/cancers13205052

Koehler Leman L, Szczerbiak P, Renfrew PD, et al. Sequence-structure-function relationships in the microbial protein universe. Nature Communications. Springer Nature. 2023;14(1):2351. doi:10.1038/s41467-023-37896-w

Azinas S, Carroni M. Cryo-EM uniqueness in structure determination of macromolecular complexes: A selected structural anthology. Current Opinion in Structural Biology. Elsevier. 2023;81:102621. doi:10.1016/j.sbi.2023.102621

Lv W, Jia X, Tang B, Ma C, Fan X, Jin X, Niu Z, Han X. In silico modeling of targeted protein degradation. European Journal of Medicinal Chemistry. Elsevier. 2025;289:117432. doi:10.1016/j.ejmech.2025.117432

Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L, Lepore R, Schwede T. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Research. 2018 Jul;46(W1):W296–W303. doi:10.1093/nar/gky427.

Varadi M, Anyango S, Deshpande M, Nair S, Natassia C, Yordanova G, Yuan D, Stroe O, Wood G, Laydon A, Žídek A, Green T, Tunyasuvunakool K, Petersen S, Jumper J, Clancy E, Green R, Vora A, Lutfi M, Figurnov M, Cowie A, Hobbs N, Kohli P, Kleywegt G, Birney E, Hassabis D, Velankar S. AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Research. 2022;50(D1):D439–D444. doi:10.1093/nar/gkab1061.

Jumper J, Evans R, Pritzel A, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596:583–589. doi:10.1038/s41586-021-03819-2.

Senior AW, Evans R, Jumper J, et al. Improved protein structure prediction using potentials from deep learning. Nature. 2020;577:706–710. doi:10.1038/s41586-019-1923-7.

Baek M, DiMaio F, Anishchenko I, et al. Accurate prediction of protein structures and interactions using a three-track neural network. Science. 2021;373(6557):871–876. doi:10.1126/science.abj8754.

Prabhash K, et al. RET Alterations Differentiate Molecular Profile of Medullary Thyroid Cancer. Journal of Clinical Oncology: Precision Oncology. 2024;8:e2300622. doi:10.1200/PO.23.00622.

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Luck K, Kim DK, Lambourne L, et al. A reference map of the human binary protein interactome. Nature. 2020;580(7803):402–408. https://doi.org/10.1038/s41586-020-2188-x

Oughtred R, Rust J, Chang C, Breitkreutz BJ, Stark C, Willems A, Boucher L, Leung G, Kolas N, Zhang F, Dolma S, Coulombe-Huntington J, Chatr-aryamontri A, Dolinski K, Tyers M. The BioGRID database: A comprehensive biomedical resource of curated protein, genetic, and chemical interactions. Protein Science. 2021;30(1):187–200.

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Hutter C, Zenklusen JC. The Cancer Genome Atlas: Creating lasting value beyond its data. Cell. Elsevier. 2018;173(2):283–285. doi:10.1016/j.cell.2018.03.042

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Sahin K, Orhan MD, Avsar T, Durdagi S. Hybrid in silico and TR-FRET-guided discovery of novel BCL-2 inhibitors. ACS Pharmacology & Translational Science. American Chemical Society. 2021;4(3):1111–1123. doi:10.1021/acsptsci.0c00210

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Comert Onder F, Durdagi S, Sahin K, Ozpolat B, Ay M. Design, Synthesis, and Molecular Modeling Studies of Novel Coumarin Carboxamide Derivatives as eEF-2K Inhibitors. Journal of Chemical Information and Modeling. American Chemical Society. 2020;60(3):1766–1778. doi:10.1021/acs.jcim.9b01083

Tamizhini L, Doss GP. Computational molecular insights into ibrutinib as a potent inhibitor of HER2-L755S mutant in breast cancer: gene expression studies, virtual screening, docking, and molecular dynamics analysis. Frontiers in Molecular Biosciences. Frontiers Media S.A. 2025;12: article 1510896. doi:10.3389/fmolb.2025.1510896

Tayubi IA, Madar IH. Identification of potential inhibitor targeting KRAS mutation in Papillary Thyroid Carcinoma through molecular docking and dynamic simulation analysis. Computers in Biology and Medicine. Elsevier. 2023;152:106377. doi:10.1016/j.compbiomed.2022.106377

Kandhare P, Kurlekar M, Deshpande T, Pawar A. Artificial intelligence in pharmaceutical sciences: A comprehensive review. Medicine in Novel Technology and Devices. Elsevier. 2025;27:100375. doi:10.1016/j.medntd.2025.100375

Deulkar P, Singam A, Jain A. A Comprehensive Review of the Role of Biomarkers in the Early Detection of Endocrine Disorders in Critical Illnesses. Cureus. 2024;31;16(5): e61409. doi: 10.7759/cureus.61409. PMID: 38947617; PMCID: PMC11214685.

Kędzierska M, Bańkosz M. Role of proteins in oncology: Advances in cancer diagnosis, prognosis, and targeted therapy—A narrative review. Journal of Clinical Medicine. MDPI. 2024;13(23):7131. doi:10.3390/jcm13237131

Kori M, Gov E, Arga KY, Sinha R. Biomarkers From Discovery to Clinical Application: In Silico Pre-Clinical Validation Approach in the Face of Lung Cancer. Biomarker Insights. SAGE Publications. 2024;3;19:11772719241287400. doi:10.1177/11772719241287400

Martins RS, Jesus TT, Cardoso L, Soares P, Vinagre J. Personalized medicine in medullary thyroid carcinoma: A broad review of emerging treatments. Journal of Personalized Medicine. 2023;13(7):1132. doi:10.3390/jpm13071132

Ramamoorthy B, Nilubol N. Multiple endocrine neoplasia type 1 syndrome pancreatic neuroendocrine tumor genotype/phenotype: Is there any advance on predicting or preventing? Surgical Oncology Clinics of North America. 2023;32(2):315–325. doi:10.1016/j.soc.2022.10.008

Colapietra F, Della Monica P, Di Napoli R, França Vieira e Silva F, Settembre G, Marino MM, Ballini A, Cantore S, Di Domenico M. Epigenetic modifications as novel biomarkers for diagnosis, prognosis, and therapeutic targeting in thyroid, pancreas, and lung neuroendocrine tumors. Journal of Clinical Medicine. 2025;14(8):2622. doi:10.3390/jcm14082622

Franchina M, Cavalcoli F, Falco O, La Milia M, Elvevi A, Massironi S. Biochemical markers for neuroendocrine tumors: Traditional circulating markers and recent development—A comprehensive review. Diagnostics. 2024;14(12):1289. doi:10.3390/diagnostics14121289

Raynor WY Kempf JS. Somatostatin Receptor PET Imaging of Physiologic and Benign Processes: Implications for Image Interpretation, Avoiding Pitfalls, and Clinical Applications. Supplement to Applied Radiology. 2024;(1):36-43.

Koffas A, Giakoustidis A, Papaefthymiou A, Bangeas P, Giakoustidis D, Papadopoulos VN, Toumpanakis C. Diagnostic work-up and advancement in the diagnosis of gastroenteropancreatic neuroendocrine neoplasms. Frontiers in Surgery. 2023;10:1064145. doi:10.3389/fsurg.2023.1064145

Uhlig R, Dum D, Gorbokon N, Menz A, Büscheck F, Luebke AM, Hube-Magg C, Hinsch A, Höflmayer D, Fraune C, Möller K, Bernreuther C, Lebok P, Weidemann S, Lennartz M, Jacobsen F, Clauditz TS, Sauter G, Wilczak W, Steurer S, Burandt E, Krech R, Krech T, Marx AH, Simon R, Minner S. Synaptophysin and chromogranin A expression analysis in human tumors. Molecular and Cellular Endocrinology. 2022;555:111726. doi:10.1016/j.mce.2022.111726

Tomita T. Significance of chromogranin A and synaptophysin in pancreatic neuroendocrine tumors. Biomolecules and Biomedicine. 2020;20(3):336–346. doi:10.17305/bjbms.2020.4632

Zhang N, Liu Q, Wang D, et al. Multifaceted roles of Galectins: from carbohydrate binding to targeted cancer therapy. Biomarker Research. 2025;13:49. doi:10.1186/s40364-025-00759-1

Tao Z, Xue R, Wei Z, Qin L, Bai R, Liu N, Wang J, Wang C. The assessment of Ki-67 for prognosis of gastroenteropancreatic neuroendocrine neoplasm patients: a systematic review and meta-analysis. Translational Cancer Research. 2023;12(8):1980–1991. doi:10.21037/tcr-23-248

Gattenlöhner S, Stühmer T, Leich E, Reinhard M, Etschmann B, Völker HU, Rosenwald A, Serfling E, Bargou RC, Ertl G, Einsele H, Müller-Hermelink HK. Specific detection of CD56 (NCAM) isoforms for the identification of aggressive malignant neoplasms with progressive development. The American Journal of Pathology. 2009;174(4):1160–1171. doi:10.2353/ajpath.2009.080647

Bahrami A, Gown A, Baird G, et al. Aberrant expression of epithelial and neuroendocrine markers in alveolar rhabdomyosarcoma: a potentially serious diagnostic pitfall. Modern Pathology. Nature Publishing Group. 2008;21(7):795–806. doi:10.1038/modpathol.2008.86

Arcolia V, Journe F, Renaud F, Leteurtre E, Gabius HJ, Remmelink M, Saussez S. Combination of galectin-3, CK19 and HBME-1 immunostaining improves the diagnosis of thyroid cancer. Oncology Letters. 2017 Oct;14(4):4183–4189. doi:10.3892/ol.2017.6719.

Peștean C, Pavel A, Piciu D. Clinical and paraclinical considerations regarding Ki-67's role in the management of differentiated thyroid carcinoma: a literature review. Medicina. 2024;60(5):769. doi:10.3390/medicina60050769.

Hellgren LS, Stenman A, Paulsson JO, Höög A, Larsson C, Zedenius J, Juhlin CC. Prognostic utility of the Ki-67 labeling index in follicular thyroid tumors: a 20-year experience from a tertiary thyroid center. Endocrine Pathology. 2022;33(2):231–242. doi:10.1007/s12022-022-09714-4.

Masui T, Yane K, Ota I, Kakudo K, Wakasa T, Koike S, Kinugawa H, Yasumatsu R, Kitahara T. Low Ki-67 labeling index is a clinically useful predictive factor for recurrence-free survival in patients with papillary thyroid carcinoma. Journal of Pathology and Translational Medicine. 2025;59(2):115–124. doi:10.4132/jptm.2024.11.08.

Prinzi A, Frasca F, Russo M, Pellegriti G, Piticchio T, Tumino D, Belfiore A, Malandrino P. Pre-operative calcitonin and CEA values may predict the extent of metastases to the lateral neck lymph nodes in patients with medullary thyroid cancer. Cancers. 2024;16(17):2979. doi:10.3390/cancers16172979.

Yoo JH, Leem DE, Kim BR, Kim TH, Kim SW, Chung JH. Medullary thyroid carcinoma detected by routine health screening had better clinical outcome and survival. Endocrinology and Metabolism. 2025;40(3):414–420.

Sipos JA, Aloi J, Gianoukakis A, Lee SL, Klopper JP, Kung JT, Lupo MA, Morgenstern D, Prat-Knoll C, Schuetzenmeister A, Goldner WS. Thyroglobulin cutoff values for detecting excellent response to therapy in patients with differentiated thyroid cancer. Journal of the Endocrine Society. 2023;7(9):bvad102. doi:10.1210/jendso/bvad102.

Sule R, Rivera G, Gomes AV. Western blotting (immunoblotting): history, theory, uses, protocol and problems. BioTechniques. 2023;75(3):99–114. doi:10.2144/btn-2022-0034

Aydin S, Emre E, Ugur K, et al. An overview of ELISA: a review and update on best laboratory practices for quantifying peptides and proteins in biological fluids. Journal of International Medical Research. SAGE Publications Ltd. 2025;53(2): doi:10.1177/03000605251315913

Abouelfadl DM, Shabana ME, Soliman ASA, Yassen NN. Evaluation of the immunohistochemical expression of Nrf2, galectin-3, and CK19 in papillary thyroid carcinoma and its mimics. Egyptian Journal of Pathology. Medknow Publications. 2024;44(2):150–158. doi:10.4103/egjp.egjp_34_24

Wenk D, Zuo C, Kislinger T, et al. Recent developments in mass-spectrometry-based targeted proteomics of clinical cancer biomarkers. Clinical Proteomics. BioMed Central. 2024;21:6. doi:10.1186/s12014-024-09452-1

Bessaad M, Habel A, Hadj Ahmed M, Xu W, Stayoussef M, Bouaziz H, Hachiche M, Mezlini A, Larbi A, Yaacoubi-Loueslati B. Assessing serum cytokine profiles in inflammatory breast cancer patients using Luminex® technology. Cytokine. Elsevier. 2023;172:156409. doi:10.1016/j.cyto.2023.156409.

Coll-de la Rubia E, Martinez-Garcia E, Dittmar G, Nazarov PV, Bebia V, Cabrera S, Gil-Moreno A, Colás E. In silico approach for validating and unveiling new applications for prognostic biomarkers of endometrial cancer. Cancers (Basel). MDPI. 2021;13(20):5052. doi:10.3390/cancers13205052

Koehler Leman L, Szczerbiak P, Renfrew PD, et al. Sequence-structure-function relationships in the microbial protein universe. Nature Communications. Springer Nature. 2023;14(1):2351. doi:10.1038/s41467-023-37896-w

Azinas S, Carroni M. Cryo-EM uniqueness in structure determination of macromolecular complexes: A selected structural anthology. Current Opinion in Structural Biology. Elsevier. 2023;81:102621. doi:10.1016/j.sbi.2023.102621

Lv W, Jia X, Tang B, Ma C, Fan X, Jin X, Niu Z, Han X. In silico modeling of targeted protein degradation. European Journal of Medicinal Chemistry. Elsevier. 2025;289:117432. doi:10.1016/j.ejmech.2025.117432

Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L, Lepore R, Schwede T. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Research. 2018 Jul;46(W1):W296–W303. doi:10.1093/nar/gky427.

Varadi M, Anyango S, Deshpande M, Nair S, Natassia C, Yordanova G, Yuan D, Stroe O, Wood G, Laydon A, Žídek A, Green T, Tunyasuvunakool K, Petersen S, Jumper J, Clancy E, Green R, Vora A, Lutfi M, Figurnov M, Cowie A, Hobbs N, Kohli P, Kleywegt G, Birney E, Hassabis D, Velankar S. AlphaFold Protein Structure Database: massively expanding the structural coverage of protein-sequence space with high-accuracy models. Nucleic Acids Research. 2022;50(D1):D439–D444. doi:10.1093/nar/gkab1061.

Jumper J, Evans R, Pritzel A, et al. Highly accurate protein structure prediction with AlphaFold. Nature. 2021;596:583–589. doi:10.1038/s41586-021-03819-2.

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