Skip to main content
Top
Published in:

09-08-2023 | Osteosarcoma | Research

Construction and validation of a predictive nomogram for ferroptosis-related genes in osteosarcoma

Authors: Jinzhi Meng, Huawei Du, Jinfeng Lu, Hongtao Wang

Published in: Journal of Cancer Research and Clinical Oncology | Issue 15/2023

Login to get access

Abstract

Background

Ferroptosis is a new type of cellular regulation of necrosis that has attracted great attention in recent years, which is different from the traditional mode of autophagy, apoptosis, and necrosis. Studies suggest that ferroptosis is key to the occurrence and development of tumors.

Methods

Here, we investigated the prognostic significance of ferroptosis-related genes (FRGs) in osteosarcoma (OS) using RNA transcriptome data from 88 OS samples collected from the UCSC Xena platform. We defined the OS sample from the UCSC platform as the training cohort and the GEO dataset (GSE21257 and GSE16091) as the validation cohorts. We assessed 73 up-regulated and 63 down-regulated FRGs. We divided patients from the UCSC database into groups at high risk and low risk and built a prognostic risk model to assess prognosis using five FRGs: MT1G, G6PD, ARNTL, BNIP3, and SQLE.

Results

High-risk OS patients presented a lower survival rate. These results were confirmed in the validation groups. In the training group, the areas under the ROC curves (AUC) were as follows: 0.880 for 1 year, 0.833 for 3 years, and 0.818 for 5 years. In the GSE21257 validation cohort, the AUC were as follows: 0.770 for 1 year, 0.641 for 3 years, and 0.632 for 5 years survival, and in the GSE16091 were 0.729 for 1 year, 0.663 for 3 years, and 0.735 for 5 years survival.

Conclusions

These findings suggest that FRGs are associated with the prognosis of osteosarcoma. Moreover, our prognostic risk model can predict overall survival in osteosarcoma. This provides new ideas for the clinical diagnosis and personalized treatment of osteosarcoma.
Appendix
Available only for authorised users
Literature
go back to reference Anderson ME (2016) Update on survival in osteosarcoma. Orthop Clin N Am 47(1):283–292 Anderson ME (2016) Update on survival in osteosarcoma. Orthop Clin N Am 47(1):283–292
go back to reference Andrews NC (1999) Disorders of iron. Metabolism 341(26):1986–1995 Andrews NC (1999) Disorders of iron. Metabolism 341(26):1986–1995
go back to reference Ashburner M, Ball CA, Blake JA et al (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25(1):25–29PubMedPubMedCentral Ashburner M, Ball CA, Blake JA et al (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25(1):25–29PubMedPubMedCentral
go back to reference Basuli D, Tesfay L, Deng Z et al (2017) Iron addiction: a novel therapeutic target in ovarian cancer. Oncogene 36(29):4089–4099PubMedPubMedCentral Basuli D, Tesfay L, Deng Z et al (2017) Iron addiction: a novel therapeutic target in ovarian cancer. Oncogene 36(29):4089–4099PubMedPubMedCentral
go back to reference Brady JJ, Chuang CH, Greenside PG et al (2016) An Arntl2-Driven secretome enables lung adenocarcinoma metastatic self-sufficiency. Cancer Cell 29(5):697–710PubMedPubMedCentral Brady JJ, Chuang CH, Greenside PG et al (2016) An Arntl2-Driven secretome enables lung adenocarcinoma metastatic self-sufficiency. Cancer Cell 29(5):697–710PubMedPubMedCentral
go back to reference Brown DN, Caffa I, Cirmena G et al (2016) Squalene epoxidase is a bona fide oncogene by amplification with clinical relevance in breast cancer. Sci Rep 6:19435PubMedPubMedCentral Brown DN, Caffa I, Cirmena G et al (2016) Squalene epoxidase is a bona fide oncogene by amplification with clinical relevance in breast cancer. Sci Rep 6:19435PubMedPubMedCentral
go back to reference Bruick RK (2000) Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc Natl Acad Sci USA 97(16):9082–9087PubMedPubMedCentral Bruick RK (2000) Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc Natl Acad Sci USA 97(16):9082–9087PubMedPubMedCentral
go back to reference Calvisi DF, Ladu S, Gorden A et al (2007) Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma. J Clin Investig 117(9):2713–2722PubMedPubMedCentral Calvisi DF, Ladu S, Gorden A et al (2007) Mechanistic and prognostic significance of aberrant methylation in the molecular pathogenesis of human hepatocellular carcinoma. J Clin Investig 117(9):2713–2722PubMedPubMedCentral
go back to reference Chen Y, Fan Z, Yang Y et al (2019) Iron metabolism and its contribution to cancer (Review). Int J Oncol 54(4):1143–1154PubMed Chen Y, Fan Z, Yang Y et al (2019) Iron metabolism and its contribution to cancer (Review). Int J Oncol 54(4):1143–1154PubMed
go back to reference Chen YC, Oses-Prieto JA, Pope LE et al (2020) Reactivity-based probe of the iron(II)-dependent interactome identifies new cellular modulators of ferroptosis. J Am Chem Soc 142(45):19085–19093PubMedPubMedCentral Chen YC, Oses-Prieto JA, Pope LE et al (2020) Reactivity-based probe of the iron(II)-dependent interactome identifies new cellular modulators of ferroptosis. J Am Chem Soc 142(45):19085–19093PubMedPubMedCentral
go back to reference Chen X, Kang R, Kroemer G et al (2021) Broadening horizons: the role of ferroptosis in cancer. Nat Rev Clin Oncol 18:280–296PubMed Chen X, Kang R, Kroemer G et al (2021) Broadening horizons: the role of ferroptosis in cancer. Nat Rev Clin Oncol 18:280–296PubMed
go back to reference Dolma S, Lessnick SL, Hahn WC et al (2003) Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3(3):285–296PubMed Dolma S, Lessnick SL, Hahn WC et al (2003) Identification of genotype-selective antitumor agents using synthetic lethal chemical screening in engineered human tumor cells. Cancer Cell 3(3):285–296PubMed
go back to reference Eling N, Reuter L, Hazin J et al (2015) Identification of artesunate as a specific activator of ferroptosis in pancreatic cancer cells. Oncoscience 2(5):517–532PubMedPubMedCentral Eling N, Reuter L, Hazin J et al (2015) Identification of artesunate as a specific activator of ferroptosis in pancreatic cancer cells. Oncoscience 2(5):517–532PubMedPubMedCentral
go back to reference Greenshields AL, Shepherd TG, Hoskin DW (2017) Contribution of reactive oxygen species to ovarian cancer cell growth arrest and killing by the anti-malarial drug artesunate. Mol Carcinog 56(1):75–93PubMed Greenshields AL, Shepherd TG, Hoskin DW (2017) Contribution of reactive oxygen species to ovarian cancer cell growth arrest and killing by the anti-malarial drug artesunate. Mol Carcinog 56(1):75–93PubMed
go back to reference Guo K, Searfoss G, Krolikowski D et al (2001) Hypoxia induces the expression of the pro-apoptotic gene BNIP3. Cell Death Differ 8(4):367–376PubMed Guo K, Searfoss G, Krolikowski D et al (2001) Hypoxia induces the expression of the pro-apoptotic gene BNIP3. Cell Death Differ 8(4):367–376PubMed
go back to reference Hassannia B, Vandenabeele P, Vanden BT (2019) Targeting ferroptosis to iron out cancer. Cancer Cell 35(6):830–849PubMed Hassannia B, Vandenabeele P, Vanden BT (2019) Targeting ferroptosis to iron out cancer. Cancer Cell 35(6):830–849PubMed
go back to reference Hong W, Yuan H, Gu Y et al (2020) Immune-related prognosis biomarkers associated with osteosarcoma microenvironment. Cancer Cell Int 20:83PubMedPubMedCentral Hong W, Yuan H, Gu Y et al (2020) Immune-related prognosis biomarkers associated with osteosarcoma microenvironment. Cancer Cell Int 20:83PubMedPubMedCentral
go back to reference Iasonos A, Schrag D, Raj GV et al (2008) How to build and interpret a nomogram for cancer prognosis. J Clin Oncol 26(8):1364–1370PubMed Iasonos A, Schrag D, Raj GV et al (2008) How to build and interpret a nomogram for cancer prognosis. J Clin Oncol 26(8):1364–1370PubMed
go back to reference Jackson TM, Bittman M, Granowetter L (2016) Pediatric malignant bone tumors: a review and update on current challenges, and emerging drug targets. Curr Probl Pediatr Adolesc Health Care 46(7):213–228PubMed Jackson TM, Bittman M, Granowetter L (2016) Pediatric malignant bone tumors: a review and update on current challenges, and emerging drug targets. Curr Probl Pediatr Adolesc Health Care 46(7):213–228PubMed
go back to reference Jawad MU, Cheung MC, Clarke J et al (2011) Osteosarcoma: improvement in survival limited to high-grade patients only. J Cancer Res Clin Oncol 137(4):597–607PubMed Jawad MU, Cheung MC, Clarke J et al (2011) Osteosarcoma: improvement in survival limited to high-grade patients only. J Cancer Res Clin Oncol 137(4):597–607PubMed
go back to reference Ji XF, Fan YC, Gao S et al (2014) MT1M and MT1G promoter methylation as biomarkers for hepatocellular carcinoma. World J Gastroenterol 20(16):4723–4729PubMedPubMedCentral Ji XF, Fan YC, Gao S et al (2014) MT1M and MT1G promoter methylation as biomarkers for hepatocellular carcinoma. World J Gastroenterol 20(16):4723–4729PubMedPubMedCentral
go back to reference Lettieri CK, Appel N, Labban N et al (2016) Progress and opportunities for immune therapeutics in osteosarcoma. Immunotherapy 8(10):1233–1244PubMed Lettieri CK, Appel N, Labban N et al (2016) Progress and opportunities for immune therapeutics in osteosarcoma. Immunotherapy 8(10):1233–1244PubMed
go back to reference Li F, Cao Y, Han L et al (2013) GeneExpressionSignature: an R package for discovering functional connections using gene expression signatures. OMICS 17(2):116–118PubMed Li F, Cao Y, Han L et al (2013) GeneExpressionSignature: an R package for discovering functional connections using gene expression signatures. OMICS 17(2):116–118PubMed
go back to reference Liu D, Wong CC, Fu L et al (2018) Squalene epoxidase drives NAFLD-induced hepatocellular carcinoma and is a pharmaceutical target. Sci Transl Med 10(437):eaap9840PubMed Liu D, Wong CC, Fu L et al (2018) Squalene epoxidase drives NAFLD-induced hepatocellular carcinoma and is a pharmaceutical target. Sci Transl Med 10(437):eaap9840PubMed
go back to reference Meazza C, Scanagatta P (2016) Metastatic osteosarcoma: a challenging multidisciplinary treatment. Expert Rev Anticancer Ther 16(5):543–556PubMed Meazza C, Scanagatta P (2016) Metastatic osteosarcoma: a challenging multidisciplinary treatment. Expert Rev Anticancer Ther 16(5):543–556PubMed
go back to reference Mirabello L, Troisi RJ, Savage SA (2009) International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer 125(1):229–234PubMedPubMedCentral Mirabello L, Troisi RJ, Savage SA (2009) International osteosarcoma incidence patterns in children and adolescents, middle ages and elderly persons. Int J Cancer 125(1):229–234PubMedPubMedCentral
go back to reference Mocellin S, Tropea S, Benna C et al (2018) Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies. BMC Med 16(1):20PubMedPubMedCentral Mocellin S, Tropea S, Benna C et al (2018) Circadian pathway genetic variation and cancer risk: evidence from genome-wide association studies. BMC Med 16(1):20PubMedPubMedCentral
go back to reference Morales-Santana S, Morell S, Leon J et al (2019) An overview of the polymorphisms of circadian genes associated with endocrine cancer. Front Endocrinol 10:104 Morales-Santana S, Morell S, Leon J et al (2019) An overview of the polymorphisms of circadian genes associated with endocrine cancer. Front Endocrinol 10:104
go back to reference Murai M, Toyota M, Suzuki H et al (2005a) Aberrant methylation and silencing of the BNIP3 gene in colorectal and gastric cancer. Clin Cancer Res 11(3):1021–1027PubMed Murai M, Toyota M, Suzuki H et al (2005a) Aberrant methylation and silencing of the BNIP3 gene in colorectal and gastric cancer. Clin Cancer Res 11(3):1021–1027PubMed
go back to reference Murai M, Toyota M, Satoh A et al (2005b) Aberrant DNA methylation associated with silencing BNIP3 gene expression in haematopoietic tumours. Br J Cancer 92(6):1165–1172PubMedPubMedCentral Murai M, Toyota M, Satoh A et al (2005b) Aberrant DNA methylation associated with silencing BNIP3 gene expression in haematopoietic tumours. Br J Cancer 92(6):1165–1172PubMedPubMedCentral
go back to reference Nirala BK, Patel TD, Kurenbekova L et al (2023) MYC regulates CSF1 expression via microRNA 17/20a to modulate tumor-associated macrophages in osteosarcoma. JCI Insight 8(13):e164947PubMedPubMedCentral Nirala BK, Patel TD, Kurenbekova L et al (2023) MYC regulates CSF1 expression via microRNA 17/20a to modulate tumor-associated macrophages in osteosarcoma. JCI Insight 8(13):e164947PubMedPubMedCentral
go back to reference Ooko E, Saeed ME, Kadioglu O et al (2015) Artemisinin derivatives induce iron-dependent cell death (ferroptosis) in tumor cells. Phytomed Int J Phytother Phytopharmacol 22(11):1045–1054 Ooko E, Saeed ME, Kadioglu O et al (2015) Artemisinin derivatives induce iron-dependent cell death (ferroptosis) in tumor cells. Phytomed Int J Phytother Phytopharmacol 22(11):1045–1054
go back to reference Pan Y, Chen D, Hu T et al (2019) Characteristics and prognostic factors of patients with osteosarcoma older than 60 years from the SEER database. Cancer Control J Moffitt Cancer Center 26(1):1073274819888893 Pan Y, Chen D, Hu T et al (2019) Characteristics and prognostic factors of patients with osteosarcoma older than 60 years from the SEER database. Cancer Control J Moffitt Cancer Center 26(1):1073274819888893
go back to reference Qin Y, Hou Y, Liu S et al (2021) A novel long non-coding RNA lnc030 maintains breast cancer stem cell stemness by stabilizing SQLE mRNA and increasing cholesterol synthesis. Adv Sci (weinheim, Baden-Wurttemberg, Germany) 8(2):2002232 Qin Y, Hou Y, Liu S et al (2021) A novel long non-coding RNA lnc030 maintains breast cancer stem cell stemness by stabilizing SQLE mRNA and increasing cholesterol synthesis. Adv Sci (weinheim, Baden-Wurttemberg, Germany) 8(2):2002232
go back to reference Sowter HM, Ratcliffe PJ, Watson P et al (2001) HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Can Res 61(18):6669–6673 Sowter HM, Ratcliffe PJ, Watson P et al (2001) HIF-1-dependent regulation of hypoxic induction of the cell death factors BNIP3 and NIX in human tumors. Can Res 61(18):6669–6673
go back to reference Stopsack KH, Gerke TA, Sinnott JA et al (2016) Cholesterol metabolism and prostate cancer lethality. Can Res 76(16):4785–4790 Stopsack KH, Gerke TA, Sinnott JA et al (2016) Cholesterol metabolism and prostate cancer lethality. Can Res 76(16):4785–4790
go back to reference Sun X, Niu X, Chen R et al (2016) Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis. Hepatology (baltimore, MD) 64(2):488–500PubMed Sun X, Niu X, Chen R et al (2016) Metallothionein-1G facilitates sorafenib resistance through inhibition of ferroptosis. Hepatology (baltimore, MD) 64(2):488–500PubMed
go back to reference Szklarczyk D, Franceschini A, Kuhn M et al (2011) The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 39(Database issue):D561-568PubMed Szklarczyk D, Franceschini A, Kuhn M et al (2011) The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res 39(Database issue):D561-568PubMed
go back to reference Tang B, Zhu J, Li J et al (2020) The ferroptosis and iron-metabolism signature robustly predicts clinical diagnosis, prognosis and immune microenvironment for hepatocellular carcinoma. Cell Commun Signal 18(1):174PubMedPubMedCentral Tang B, Zhu J, Li J et al (2020) The ferroptosis and iron-metabolism signature robustly predicts clinical diagnosis, prognosis and immune microenvironment for hepatocellular carcinoma. Cell Commun Signal 18(1):174PubMedPubMedCentral
go back to reference Wang T, Ji F, Dai Z et al (2015) Increased expression of microRNA-191 as a potential serum biomarker for diagnosis and prognosis in human osteosarcoma. Cancer Biomark Sect A Dis Mark 15(5):543–550 Wang T, Ji F, Dai Z et al (2015) Increased expression of microRNA-191 as a potential serum biomarker for diagnosis and prognosis in human osteosarcoma. Cancer Biomark Sect A Dis Mark 15(5):543–550
go back to reference Wei R, Thanindratarn P, Dean DC et al (2020) Cyclin E1 is a prognostic biomarker and potential therapeutic target in osteosarcoma. J Orthop Res 38(9):1952–1964PubMed Wei R, Thanindratarn P, Dean DC et al (2020) Cyclin E1 is a prognostic biomarker and potential therapeutic target in osteosarcoma. J Orthop Res 38(9):1952–1964PubMed
go back to reference Wu ZL, Deng YJ, Zhang GZ et al (2020) Development of a novel immune-related genes prognostic signature for osteosarcoma. Sci Rep 10(1):18402PubMedPubMedCentral Wu ZL, Deng YJ, Zhang GZ et al (2020) Development of a novel immune-related genes prognostic signature for osteosarcoma. Sci Rep 10(1):18402PubMedPubMedCentral
go back to reference Yamaguchi H, Hsu JL, Chen CT et al (2013) Caspase-independent cell death is involved in the negative effect of EGF receptor inhibitors on cisplatin in non-small cell lung cancer cells. Clin Cancer Res 19(4):845–854PubMedPubMedCentral Yamaguchi H, Hsu JL, Chen CT et al (2013) Caspase-independent cell death is involved in the negative effect of EGF receptor inhibitors on cisplatin in non-small cell lung cancer cells. Clin Cancer Res 19(4):845–854PubMedPubMedCentral
go back to reference Yang WS, SriRamaratnam R, Welsch ME et al (2014) Regulation of ferroptotic cancer cell death by GPX4. Cell 156(1–2):317–331PubMedPubMedCentral Yang WS, SriRamaratnam R, Welsch ME et al (2014) Regulation of ferroptotic cancer cell death by GPX4. Cell 156(1–2):317–331PubMedPubMedCentral
go back to reference Yang Z, Zhang Y, Zhang X et al (2015) Serum microRNA-221 functions as a potential diagnostic and prognostic marker for patients with osteosarcoma. Biomed Pharmacother Biomed Pharmacother 75:153–158PubMed Yang Z, Zhang Y, Zhang X et al (2015) Serum microRNA-221 functions as a potential diagnostic and prognostic marker for patients with osteosarcoma. Biomed Pharmacother Biomed Pharmacother 75:153–158PubMed
go back to reference Ye F, Wang H, Zhang L et al (2015) Baicalein induces human osteosarcoma cell line MG-63 apoptosis via ROS-induced BNIP3 expression. Tumour Biol J Int Soc Oncodev Biol Med 36(6):4731–4740 Ye F, Wang H, Zhang L et al (2015) Baicalein induces human osteosarcoma cell line MG-63 apoptosis via ROS-induced BNIP3 expression. Tumour Biol J Int Soc Oncodev Biol Med 36(6):4731–4740
go back to reference Yu H, Guo P, Xie X et al (2017) Ferroptosis, a new form of cell death, and its relationships with tumourous diseases. J Cell Mol Med 21(4):648–657PubMed Yu H, Guo P, Xie X et al (2017) Ferroptosis, a new form of cell death, and its relationships with tumourous diseases. J Cell Mol Med 21(4):648–657PubMed
go back to reference Zhang J, Ney PA (2009) Role of BNIP3 and NIX in cell death, autophagy, and mitophagy. Cell Death Differ 16(7):939–946PubMed Zhang J, Ney PA (2009) Role of BNIP3 and NIX in cell death, autophagy, and mitophagy. Cell Death Differ 16(7):939–946PubMed
go back to reference Zhang C, Zhang Z, Zhu Y et al (2014) Glucose-6-phosphate dehydrogenase: a biomarker and potential therapeutic target for cancer. Anticancer Agents Med Chem 14(2):280–289PubMed Zhang C, Zhang Z, Zhu Y et al (2014) Glucose-6-phosphate dehydrogenase: a biomarker and potential therapeutic target for cancer. Anticancer Agents Med Chem 14(2):280–289PubMed
go back to reference Zhang J, Wang X, Wu W et al (2016) Expression of the Nrf2 and Keap1 proteins and their clinical significance in osteosarcoma. Biochem Biophys Res Commun 473(1):42–46PubMed Zhang J, Wang X, Wu W et al (2016) Expression of the Nrf2 and Keap1 proteins and their clinical significance in osteosarcoma. Biochem Biophys Res Commun 473(1):42–46PubMed
go back to reference Zhang Z, Yuan L, Liu Y et al (2023) Integrated cascade nanozyme remodels chondrocyte inflammatory microenvironment in temporomandibular joint osteoarthritis via inhibiting ROS-NF-κB and MAPK pathways. Adv Healthc Mater 4:e2203195 Zhang Z, Yuan L, Liu Y et al (2023) Integrated cascade nanozyme remodels chondrocyte inflammatory microenvironment in temporomandibular joint osteoarthritis via inhibiting ROS-NF-κB and MAPK pathways. Adv Healthc Mater 4:e2203195
go back to reference Zhou N, Bao J (2020) FerrDb: a manually curated resource for regulators and markers of ferroptosis and ferroptosis-disease associations. Database J Biol Databases Curation 2020:1–8 Zhou N, Bao J (2020) FerrDb: a manually curated resource for regulators and markers of ferroptosis and ferroptosis-disease associations. Database J Biol Databases Curation 2020:1–8
go back to reference Zhou L, Zhao B, Zhang L et al (2018) Alterations in cellular iron metabolism provide more therapeutic opportunities for cancer. Int J Mol Sci 19(5):1545 Zhou L, Zhao B, Zhang L et al (2018) Alterations in cellular iron metabolism provide more therapeutic opportunities for cancer. Int J Mol Sci 19(5):1545
Metadata
Title
Construction and validation of a predictive nomogram for ferroptosis-related genes in osteosarcoma
Authors
Jinzhi Meng
Huawei Du
Jinfeng Lu
Hongtao Wang
Publication date
09-08-2023
Publisher
Springer Berlin Heidelberg
Published in
Journal of Cancer Research and Clinical Oncology / Issue 15/2023
Print ISSN: 0171-5216
Electronic ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-023-05225-9

Other articles of this Issue 15/2023

Journal of Cancer Research and Clinical Oncology 15/2023 Go to the issue

Keynote webinar | Spotlight on adolescent vaping

  • Live
  • Webinar | 29-01-2025 | 18:00 (CET)

Live: Wednesday 29th January, 18:00-19:30 CET

Growing numbers of young people are using e-cigarettes, despite warnings of respiratory effects and addiction. How can doctors tackle the epidemic, and what health effects should you prepare to manage in your clinics?

Prof. Ann McNeill
Dr. Debbie Robson
Benji Horwell
Developed by: Springer Medicine
Join the webinar

Keynote webinar | Spotlight on modern management of frailty

Frailty has a significant impact on health and wellbeing, especially in older adults. Our experts explain the factors that contribute to the development of frailty and how you can manage the condition and reduce the risk of disability, dependency, and mortality in your patients.

Prof. Alfonso Cruz-Jentoft
Prof. Barbara C. van Munster
Prof. Mirko Petrovic
Developed by: Springer Medicine
Watch now

A quick guide to ECGs

Improve your ECG interpretation skills with this comprehensive, rapid, interactive course. Expert advice provides detailed feedback as you work through 50 ECGs covering the most common cardiac presentations to ensure your practice stays up to date. 

PD Dr. Carsten W. Israel
Developed by: Springer Medizin
Start the cases

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine
Read more