Skip to main content

Main menu

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Editorial Policies
    • Advertisers
    • Editorial Board
  • Other Publications
    • Anticancer Research
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
  • About Us
    • General Policy
    • Contact
  • Other Publications
    • In Vivo
    • Anticancer Research
    • Cancer Genomics & Proteomics

User menu

  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
In Vivo
  • Other Publications
    • In Vivo
    • Anticancer Research
    • Cancer Genomics & Proteomics
  • Register
  • Subscribe
  • My alerts
  • Log in
  • My Cart
In Vivo

Advanced Search

  • Home
  • Current Issue
  • Archive
  • Info for
    • Authors
    • Editorial Policies
    • Advertisers
    • Editorial Board
  • Other Publications
    • Anticancer Research
    • Cancer Genomics & Proteomics
    • Cancer Diagnosis & Prognosis
  • More
    • IIAR
    • Conferences
  • About Us
    • General Policy
    • Contact
  • Visit iiar on Facebook
  • Follow us on Linkedin
Research ArticleClinical Studies

Evaluation of Serum Biomarkers (FGF-2, HGF, MIF and PTN) in Patients With Testicular Germ Cell Cancer

STEFAN HAUSER, ANNETTE KAMINSKI, ISABELLA SYRING, STEFAN HOLDENRIEDER, KLAUS-PETER DIECKMANN, STEFAN C. MULLER and JORG ELLINGER
In Vivo November 2019, 33 (6) 1935-1940; DOI: https://doi.org/10.21873/invivo.11688
STEFAN HAUSER
1Universitätsklinikum Bonn, Klinik und Poliklinik für Urologie und Kinderurologie, Bonn, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: stefan.hauser@ukbonn.de
ANNETTE KAMINSKI
1Universitätsklinikum Bonn, Klinik und Poliklinik für Urologie und Kinderurologie, Bonn, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
ISABELLA SYRING
1Universitätsklinikum Bonn, Klinik und Poliklinik für Urologie und Kinderurologie, Bonn, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
STEFAN HOLDENRIEDER
2Universitätsklinikum Bonn, Institut für Klinische Chemie und Klinische Pharmakologie, Bonn, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
KLAUS-PETER DIECKMANN
3Albertinen Krankenhaus, Klinik für Urologie, Hamburg, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
STEFAN C. MULLER
1Universitätsklinikum Bonn, Klinik und Poliklinik für Urologie und Kinderurologie, Bonn, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
JORG ELLINGER
1Universitätsklinikum Bonn, Klinik und Poliklinik für Urologie und Kinderurologie, Bonn, Germany
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Background/Aim: FGF-2, HGF, MIF and PTN have been suggested as biomarkers for testicular germ cell cancer patients in earlier studies. Our study was designed to validate these potential novel tumor markers. Materials and Methods: Serum FGF-2, HGF, MIF and PTN levels were analysed using an ELISA technique in a screening cohort of 20 testicular germ cell cancer patients and 10 healthy men. MIF levels were measured in a validation cohort of 84 patients with testicular cancer, 24 with non-malignant testicular tumors and 64 healthy men. Results: Serum FGF-2, HGF and PTN levels did not differ in cancer patients and healthy males within the screening cohort, whereas MIF was significantly increased among cancer patients. Within the validation cohort, a modest but insignificant increase of serum MIF was observed in TGCT patients compared to healthy men. MIF levels were not correlated with adverse clinical-pathological parameters. Conclusion: FGF-2, HGF, MIF and PTN are not suitable as non-invasive biomarkers for testicular germ cell cancer patients.

  • Testicular cancer
  • biomarker
  • serum
  • MIF
  • FGF
  • HGF
  • PTN
  • ELISA
  • diagnosis

Testicular germ cell cancer (TGCT) is the most common malignancy in young men. The incidence of TGCT is still rising in many western countries, while mortality rates remain low. The successful treatment of patients with even advanced metastatic TGCT is mainly due to the effective multimodal therapy (polychemotherapy, radiotherapy and surgery) (1). The serum tumor markers alpha-fetoprotein (AFP) and human chorionic gonadotropin (hCG) are used for diagnosis, risk stratification, treatment monitoring, and surveillance (2). However, both biomarkers lack high sensitivity, especially in early tumor stages and seminoma TGCT patients. It is estimated that about 50% of TGCT patients have normally ranged tumor markers (3). Thus, novel non-invasive tumor markers with improved sensitivity could help improve the clinical management of TGCT patients.

A variety of potential TGCT biomarkers including circulating nucleic acids [e.g. microRNA (4, 5), DNA methylation (6), DNA concentration (7)] and serum proteins [e.g. Fas ligand (8), TNFRSF8 (9)] have been evaluated, but none of them have yet been applied in daily routine due to the lack of validation studies and the small case numbers (10). Aigner et al. reported in 2003 an increase in serum FGF-2 (fibroblast growth factor-2) and PTN (pleiotrophin) levels in TGCT patients (n=22) compared to healthy individuals (n=21) (11); both proteins are involved in tumor angiogenesis. Serum PTN [e.g. colorectal (12), lung (13), pancreatic (12)] and FGF-2 [e.g. colorectal (14), ovarian (15), lung (16)] levels were also increased in other cancer patients, indicating the possible diagnostic role of these proteins. In a recent study, we investigated the circulating levels of various cytokines in patients with human malignancies including TGCT patients. Among these, MIF (macrophage migration inhibitory factor) and HGF (hepatocyte growth factor) were significantly increased in TGCT patients compared to control subjects. In order to validate the findings of these earlier studies, we investigated serum biomarker levels in an enlarged cohort of patients with malignant and benign testicular disease, as well as in healthy men.

Materials and Methods

Sample collection. First, we investigated the serum concentration of FGF-2, HGF, MIF and PTN in a screening cohort of 20 testicular germ cell cancer patients (10 seminoma and 10 non-seminoma patients) and 10 healthy subjects; see Table I for clinical-pathological parameters. The validation of MIF expression levels was then performed in 108 patients undergoing inguinal exploration suspicious for testicular cancer; among these, 84 patients had malignant testicular germ cell cancer (seminoma n=48, non-seminoma n=35) and 24 had non-malignant diseases (histological diagnosis: intratubular germ cell neoplasia n=1; epidermoid cyst n=6; leydig cell tumor n=6; sertoli cell tumor n=1; mature teratoma n=2; adenomatoid tumor n=2; testicular infarction n=1; infection n=1; stromal spindle cell tumor n=1; scar tissue n=1; fibroma n=1; fibrosis n=1). We also studied an age-matched control cohort that consisted of 64 healthy male individuals. The detailed clinicopathological parameters are provided in Table II.

The collection of serum samples was performed according to local standard operating procedures within the framework of the Biobank initiative at the CIO Köln/Bonn. In brief, venous blood was collected in Serum S-Monovette Gel tubes with clotting activator (Sarstedt, Nümbrecht, Germany) prior to surgery. Serum was centrifuged after clotting for 10 min at 2500 g; the separated serum samples were stored in cryotubes at −80°C until use. Sample collection was performed between 1997 and 2014. Written informed consent was obtained from each individual and the study was approved by the local ethic committee (approval number: 162/14). The study conformed with The Code of Ethics of The World Medical Association (“Declaration of Helsinki”).

ELISA. The serum levels of FGF-2 (Quantikine FGF Immunoassay; R&D Systems, Minneapolis, MN, USA), HGF (Quantikine HGF Immunoassay; R&D Systems), MIF (Quantikine MIF Immunoassay; R&D Systems) and PTN (ELISA Kit for Pleiotrophin; Cloud-Clone, Houston, TX, USA) were quantified using ELISA kits according to the manufacturer's recommendations. We used 50 μl (MIF) or 100 μl (FGF-2, HGF, PTN) of serum for the analysis; each sample was measured in duplicate. A standard curve was constructed using the supplied standard to determine serum protein levels. The optical density of each well was detected at 450 nm on an SLT-reader (Tecan, Crailsheim, Germany).

Statistical analysis. The Mann-Whitney U-test and the Kruskal-Wallis-test were used to determine differences between cancer patients and controls, and to associate MIF expression with clinical-pathological parameters. The Pearson test was used to correlate AFP/HCG with MIF levels. The diagnostic sensitivity and specificity of the biomarkers was determined using receiver operator curve (ROC) analyses. Statistical significance was concluded at p<0.05; statistical analyses were performed using SPSS Statistics v22 (IBM, Chicago, IL, USA).

Results

Screening cohort. The serum levels of FGF-2, HGF, MIF and PTN were determined in a screening cohort of 10 seminoma and 10 non-seminoma patients, as well as 10 healthy male individuals (Figure 1). FGF-2, HGF and MIF were detected in all study patients. PTN was not detected in non-seminoma patients and only in one individual of the control group, whereas it was detectable in all seminoma patients. The serum levels of MIF were significantly increased in TGCT compared to healthy individuals (mean 7.47 ng/ml vs. 3.17 ng/ml; p=0.005), whereas FGF-2 (p=0.965) and HGF (p=0.965) were similar in both cohorts. Mean serum levels of all markers were similar in non-seminoma and seminoma TGCT patients (FGF-2 p=0.307; HGF p=0.880; MIF p=0.762). MIF levels were higher in seminoma (p=0.013) and non-seminoma (p=0.019) patients compared to controls (Figure 1).

Validation cohort. In order to validate the potential of MIF as a novel TGCT biomarker, we investigated its serum concentration in a larger cohort which included 84 patients with testicular cancer (seminoma n=48, non-seminoma n=35), 64 healthy male individuals and 24 patients with non-malignant testicular disease. The mean level of MIF was 5.05 ng/ml in TGCT patients, 4.03 ng/ml in healthy men and 5.83 ng/ml in patients with benign testicular disease. Thus, MIF levels in serum were neither different in cancer patients and healthy male (p=0.071) nor in patients with benign testicular disease (p=0.221). However, MIF was increased in patients with benign testicular disease compared to healthy male (p=0.019). MIF levels were similar in seminoma and non-seminoma TGCT (p=0.414). Thus, serum MIF levels failed as a diagnostic biomarker: the area under curve was 0.541 (95% confidence interval 0.454-0.627) for cancer patients vs. healthy male and benign patients, and 0.587 (0.495-0.679) for cancer patients vs. healthy males, respectively (Figure 2). We also investigated whether MIF levels were correlated with clinical-pathological parameters: advanced pathological stage (pT1 vs. pT3 p=0.045; pT2 vs. pT3 p=0.039) was associated with MIF levels (mean: pT1 5.04 ng/ml, pT2 4.54 ng/ml, pT3 7.62 ng/ml). Clinical tumor stage, IGCCCG stage and serum tumor markers (AFP, HCG) were not correlated with serum MIF concentrations (all p>0.1).

Discussion

Novel non-invasive tumor markers with improved sensitivity compared to the classical markers AFP and hCG could improve the clinical management of TGCT patients. In former studies, several proteins including FGF-2 (fibroblast growth factor-2) (11), PTN (pleiotrophin) (11), MIF (macrophage migration inhibitory factor; Stefan Holdenrieder et al., unpublished data) and HFG (hepatocyte growth factor; Stefan Holdenrieder et al., unpublished data) markers have been investigated in small TGCT cohorts with promising results. However, all candidate markers still require validation in independent cohorts and therefore we determined the serum levels of these markers in an enlarged cohort of patients with TGCT, non-malignant testicular disease and healthy men.

We first determined FGF-2, HGF, MIF and PTN levels in a screening cohort. Surprisingly, PTN was not detected in most patients, and HFG and FGF-2 were not differentially expressed in TGCT patients and healthy men. Thus, our study does not confirm a role of these proteins for diagnostic purposes in patients with TGCT. It should be noted that Aigner et al. used a self-constructed ELISA using a monoclonal antibody to measure PTN levels in serum (11), whereas a commercial ELISA kit from Cloud-Clone was used in this study. Similar to Aigner et al., we used the R&D Quantikine ELISA assay to determine FGF-2 levels, thereby limiting the bias due to different detection techniques. It should also be noted that PTN [colorectal (12), lung (13), pancreatic (12)] and FGF-2 [colorectal (14), ovarian (15), lung (16)] levels were also increased in other tumor entities, thus the biomarker would lack specificity and would be of limited clinical value.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table I.

Clinical-pathological parameters of patients investigated in the screening experiments.

View this table:
  • View inline
  • View popup
  • Download powerpoint
Table II.

Clinical-pathological parameters of patients investigated in the validation experiment.

Figure 1.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 1.

Screening cohort: Analysis of serum levels of FGF-2, HGF, MIF and PTN in patients with seminoma (S, n=10) and non-seminoma (NS, n=10) testicular germ cell cancer and healthy men (CTRL, n=10). The concentration of MIF was significantly increased in cancer patients.

MIF levels were significantly increased in TGCT patients in the screening cohort of 30 study subjects, and were thus further investigated in an independent validation group consisting of 172 subjects. However, we did not observe a difference in MIF levels in TGCT patients, men with non-malignant testicular disease and healthy men. This finding highlights the need for validation of candidate biomarkers in independent and large-scaled cohorts which would also include relevant control subjects (i.e. non-malignant testicular tumors). Notably, we identified several expression profiling studies (17-20) showing increased MIF levels in seminoma TGCT compared to normal testis tissue using the NextBio database (21). A role for MIF as a diagnostic biomarker has been observed in other malignancies: e.g. serum MIF levels were increased in oral carcinoma (22), hepatocellular carcinoma (23), breast cancer (24), and ovarian cancer patients (25). Interestingly, a polymorphism in the MIF promoter region (-173G/C) was associated with an increased cancer risk (26).

Conclusion

Our study failed to confirm any diagnostic value for FGF-2, HGF, MIF and PTN in patients with TGCT.

Figure 2.
  • Download figure
  • Open in new tab
  • Download powerpoint
Figure 2.

Validation cohort: Analysis of MIF serum levels in patients with testicular germ cell cancer (TCGT, seminoma, n=48; non-seminoma, n=35), healthy men (CTRL, n=64) and patients with various benign testicular tumors/diseases (n=24). The concentration of MIF did not differ in cancer patients and control subjects. AUC: Area under curve; 95%CI:95% confidence interval.

Footnotes

  • Authors' Contributions

    All Authors made substantial contributions to the conception, design, and acquisition of data. AK performed the experiments. AK, IS and JE analysed and interpreted the data. JE and SH designed the study. AK and JE drafted the manuscript. Samples were provided by KPD and SCM. IS, SH, KPD and SCM revised the manuscript. All Authors read and approved the final manuscript.

  • This article is freely accessible online.

  • Conflicts of Interest

    The Authors declare that they have no competing interests regarding this study.

  • Received July 11, 2019.
  • Revision received July 28, 2019.
  • Accepted August 1, 2019.
  • Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved

References

  1. ↵
    1. Shanmugalingam T,
    2. Soultati A,
    3. Chowdhury S,
    4. Rudman S,
    5. Van Hemelrijck M
    : Global incidence and outcome of testicular cancer. Clin Epidemiol 5: 417-427, 2013. PMID: 24204171. DOI: 10.2147/CLEP.S34430
    OpenUrl
  2. ↵
    1. Salem M,
    2. Gilligan T
    : Serum tumor markers and their utilization in the management of germ-cell tumors in adult males. Expert Rev Anticancer Ther 11(1): 1-4, 2011. PMID: 21166503. DOI: 10.1586/era.10.219
    OpenUrlCrossRefPubMed
  3. ↵
    1. Albers P,
    2. Albrecht W,
    3. Algaba F,
    4. Bokemeyer C,
    5. Cohn-Cedermark G,
    6. Fizazi K,
    7. Horwich A,
    8. Laguna MP
    : Eau guidelines on testicular cancer: 2011 update. Eur Urol 60(2): 304-319, 2011. PMID: 21632173. DOI: 10.1016/j.eururo.2011.05.038
    OpenUrlCrossRefPubMed
  4. ↵
    1. Syring I,
    2. Bartels J,
    3. Holdenrieder S,
    4. Kristiansen G,
    5. Muller SC,
    6. Ellinger J
    : Circulating serum mirna (mir-367-3p, mir-371a-3p, mir-372-3p and mir-373-3p) as biomarkers in patients with testicular germ cell cancer. J Urol 193(1): 331-337, 2015. PMID: 25046619. DOI: 10.1016/j.juro.2014.07.010
    OpenUrlPubMed
  5. ↵
    1. Dieckmann KP,
    2. Spiekermann M,
    3. Balks T,
    4. Flor I,
    5. Loning T,
    6. Bullerdiek J,
    7. Belge G
    : Micrornas mir-371-3 in serum as diagnostic tools in the management of testicular germ cell tumours. Br J Cancer 107(10): 1754-1760, 2012. PMID: 23059743. DOI: 10.1038/bjc.2012.469
    OpenUrlCrossRefPubMed
  6. ↵
    1. Ellinger J,
    2. Albers P,
    3. Perabo FG,
    4. Muller SC,
    5. von Ruecker A,
    6. Bastian PJ
    : Cpg island hypermethylation of cell-free circulating serum DNA in patients with testicular cancer. J Urol 182(1): 324-329, 2009. PMID: 19447423. DOI: 10.1016/j.juro.2009.02.106
    OpenUrlCrossRefPubMed
  7. ↵
    1. Ellinger J,
    2. Wittkamp V,
    3. Albers P,
    4. Perabo FG,
    5. Mueller SC,
    6. von Ruecker A,
    7. Bastian PJ
    : Cell-free circulating DNA: Diagnostic value in patients with testicular germ cell cancer. J Urol 181(1): 363-371, 2009. PMID: 19010497. DOI: 10.1016/j.juro.2008.08.118
    OpenUrlPubMed
  8. ↵
    1. Hara S,
    2. Miyake H,
    3. Nakamura I,
    4. Arakawa S,
    5. Kamidono S,
    6. Hara I
    : Increased fas ligand expression in the tumor tissue and serum of patients with testicular germ cell tumors with seminomatous elements. Urology 58(3): 471-476, 2001. PMID: 11549508. DOI: 10.1016/s0090-4295(01)01172-4
    OpenUrlCrossRefPubMed
  9. ↵
    1. Latza U,
    2. Foss HD,
    3. Durkop H,
    4. Eitelbach F,
    5. Dieckmann KP,
    6. Loy V,
    7. Unger M,
    8. Pizzolo G,
    9. Stein H
    : Cd30 antigen in embryonal carcinoma and embryogenesis and release of the soluble molecule. Am J Pathol 146(2): 463-471, 1995. PMID: 7856755.
    OpenUrlPubMed
  10. ↵
    1. Syring I,
    2. Mueller SC,
    3. Ellinger J
    : Novel tumor markers in the serum of testicular germ cell cancer patients: A review. Current Biomarker Findings 4: 133-137, 2014. DOI: 10.2147/CBF.S66068
    OpenUrl
  11. ↵
    1. Aigner A,
    2. Brachmann P,
    3. Beyer J,
    4. Jager R,
    5. Raulais D,
    6. Vigny M,
    7. Neubauer A,
    8. Heidenreich A,
    9. Weinknecht S,
    10. Czubayko F,
    11. Zugmaier G
    : Marked increase of the growth factors pleiotrophin and fibroblast growth factor-2 in serum of testicular cancer patients. Ann Oncol 14(10): 1525-1529, 2003. PMID: 14504053. DOI: 10.1093/annonc/mdg416
    OpenUrlCrossRefPubMed
  12. ↵
    1. Souttou B,
    2. Juhl H,
    3. Hackenbruck J,
    4. Rockseisen M,
    5. Klomp HJ,
    6. Raulais D,
    7. Vigny M,
    8. Wellstein A
    : Relationship between serum concentrations of the growth factor pleiotrophin and pleiotrophin-positive tumors. J Natl Cancer Inst 90(19): 1468-1473, 1998. PMID: 9776412. DOI: 10.1093/jnci/90.19.1468
    OpenUrlCrossRefPubMed
  13. ↵
    1. Jager R,
    2. List B,
    3. Knabbe C,
    4. Souttou B,
    5. Raulais D,
    6. Zeiler T,
    7. Wellstein A,
    8. Aigner A,
    9. Neubauer A,
    10. Zugmaier G
    : Serum levels of the angiogenic factor pleiotrophin in relation to disease stage in lung cancer patients. Br J Cancer 86(6): 858-863, 2002. PMID: 11953815. DOI: 10.1038/sj.bjc.6600202
    OpenUrlCrossRefPubMed
  14. ↵
    1. Landriscina M,
    2. Cassano A,
    3. Ratto C,
    4. Longo R,
    5. Ippoliti M,
    6. Palazzotti B,
    7. Crucitti F,
    8. Barone C
    : Quantitative analysis of basic fibroblast growth factor and vascular endothelial growth factor in human colorectal cancer. Br J Cancer 78(6): 765-770, 1998. PMID: 9743297. DOI: 10.1038/bjc.1998.575
    OpenUrlPubMed
  15. ↵
    1. Madsen CV,
    2. Steffensen KD,
    3. Olsen DA,
    4. Waldstrom M,
    5. Sogaard CH,
    6. Brandslund I,
    7. Jakobsen A
    : Serum platelet-derived growth factor and fibroblast growth factor in patients with benign and malignant ovarian tumors. Anticancer Res 32(9): 3817-3825, 2012. PMID: 22993324.
    OpenUrlAbstract/FREE Full Text
  16. ↵
    1. Keeley BR,
    2. Islami F,
    3. Pourshams A,
    4. Poustchi H,
    5. Pak JS,
    6. Brennan P,
    7. Khademi H,
    8. Genden EM,
    9. Abnet CC,
    10. Dawsey SM,
    11. Boffetta P,
    12. Malekzadeh R,
    13. Sikora AG
    : Prediagnostic serum levels of inflammatory biomarkers are correlated with future development of lung and esophageal cancer. Cancer Sci 105(9): 1205-1211, 2014. PMID: 25040886. DOI: 10.1111/cas.12485
    OpenUrl
  17. ↵
    1. Palmer RD,
    2. Murray MJ,
    3. Saini HK,
    4. van Dongen S,
    5. Abreu-Goodger C,
    6. Muralidhar B,
    7. Pett MR,
    8. Thornton CM,
    9. Nicholson JC,
    10. Enright AJ,
    11. Coleman N
    : Malignant germ cell tumors display common microrna profiles resulting in global changes in expression of messenger rna targets. Cancer Res 70(7): 2911-2923, 2010. PMID: 20332240. DOI: 10.1158/0008-5472.CAN-09-3301
    OpenUrlAbstract/FREE Full Text
    1. Gashaw I,
    2. Grummer R,
    3. Klein-Hitpass L,
    4. Dushaj O,
    5. Bergmann M,
    6. Brehm R,
    7. Grobholz R,
    8. Kliesch S,
    9. Neuvians TP,
    10. Schmid KW,
    11. von Ostau C,
    12. Winterhager E
    : Gene signatures of testicular seminoma with emphasis on expression of ets variant gene 4. Cell Mol Life Sci 62(19-20): 2359-2368, 2005. PMID: 16158187. DOI: 10.1007/s00018-005-5250-9
    OpenUrlCrossRefPubMed
    1. Murray MJ,
    2. Halsall DJ,
    3. Hook CE,
    4. Williams DM,
    5. Nicholson JC,
    6. Coleman N
    : Identification of micrornas from the mir-371~373 and mir-302 clusters as potential serum biomarkers of malignant germ cell tumors. Am J Clin Pathol 135(1): 119-125, 2011. PMID: 21173133. DOI: 10.1309/AJCPOE11KEYZCJHT
    OpenUrlCrossRefPubMed
  18. ↵
    1. Korkola JE,
    2. Houldsworth J,
    3. Chadalavada RS,
    4. Olshen AB,
    5. Dobrzynski D,
    6. Reuter VE,
    7. Bosl GJ,
    8. Chaganti RS
    : Down-regulation of stem cell genes, including those in a 200-kb gene cluster at 12p13.31, is associated with in vivo differentiation of human male germ cell tumors. Cancer Res 66(2): 820-827, 2006. PMID: 16424014. DOI: 10.1158/0008-5472.CAN-05-2445
    OpenUrlAbstract/FREE Full Text
  19. ↵
    1. Kupershmidt I,
    2. Su QJ,
    3. Grewal A,
    4. Sundaresh S,
    5. Halperin I,
    6. Flynn J,
    7. Shekar M,
    8. Wang H,
    9. Park J,
    10. Cui W,
    11. Wall GD,
    12. Wisotzkey R,
    13. Alag S,
    14. Akhtari S,
    15. Ronaghi M
    : Ontology-based meta-analysis of global collections of high-throughput public data. PLoS One 5(9), 2010. PMID: 20927376. DOI: 10.1371/journal.pone.0013066
  20. ↵
    1. de Souza MB,
    2. Curioni OA,
    3. Kanda JL,
    4. MB DEC
    : Serum and salivary macrophage migration inhibitory factor in patients with oral squamous cell carcinoma. Oncol Lett 8(5): 2267-2275, 2014. PMID: 25289107. DOI: 10.3892/ol.2014.2513
    OpenUrl
  21. ↵
    1. Kamel MM,
    2. Saad MF,
    3. Mahmoud AA,
    4. Edries AA,
    5. Abdel-Moneim AS
    : Evaluation of serum pivka-ii and mif as diagnostic markers for hcv/hbv induced hepatocellular carcinoma. Microb Pathog 77: 31-35, 2014. PMID: 25448465. DOI: 10.1016/j.micpath.2014.10.009
    OpenUrl
  22. ↵
    1. Fersching DM,
    2. Nagel D,
    3. Siegele B,
    4. Salat C,
    5. Heinemann V,
    6. Holdenrieder S,
    7. Stoetzer OJ
    : Apoptosis-related biomarkers sfas, mif, icam-1 and pai-1 in serum of breast cancer patients undergoing neoadjuvant chemotherapy. Anticancer Res 32(5): 2047-2058, 2012. PMID: 22593487.
    OpenUrlAbstract/FREE Full Text
  23. ↵
    1. Krockenberger M,
    2. Kranke P,
    3. Hausler S,
    4. Engel JB,
    5. Horn E,
    6. Nurnberger K,
    7. Wischhusen J,
    8. Dietl J,
    9. Honig A
    : Macrophage migration-inhibitory factor levels in serum of patients with ovarian cancer correlates with poor prognosis. Anticancer Res 32(12): 5233-5238, 2012. PMID: 23225421.
    OpenUrlAbstract/FREE Full Text
  24. ↵
    1. Zhang X,
    2. Weng W,
    3. Xu W,
    4. Wang Y,
    5. Yu W,
    6. Tang X,
    7. Ma L,
    8. Pan Q,
    9. Wang J,
    10. Sun F
    : The association between the migration inhibitory factor -173g/c polymorphism and cancer risk: A meta-analysis. Onco Targets Ther 8: 601-613, 2015. PMID: 25792844. DOI: 10.2147/OTT.S72795
    OpenUrl
PreviousNext
Back to top

In this issue

In Vivo: 33 (6)
In Vivo
Vol. 33, Issue 6
November-December 2019
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • Ed Board (PDF)
  • Front Matter (PDF)
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on In Vivo.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Evaluation of Serum Biomarkers (FGF-2, HGF, MIF and PTN) in Patients With Testicular Germ Cell Cancer
(Your Name) has sent you a message from In Vivo
(Your Name) thought you would like to see the In Vivo web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
10 + 4 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Citation Tools
Evaluation of Serum Biomarkers (FGF-2, HGF, MIF and PTN) in Patients With Testicular Germ Cell Cancer
STEFAN HAUSER, ANNETTE KAMINSKI, ISABELLA SYRING, STEFAN HOLDENRIEDER, KLAUS-PETER DIECKMANN, STEFAN C. MULLER, JORG ELLINGER
In Vivo Nov 2019, 33 (6) 1935-1940; DOI: 10.21873/invivo.11688

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Reprints and Permissions
Share
Evaluation of Serum Biomarkers (FGF-2, HGF, MIF and PTN) in Patients With Testicular Germ Cell Cancer
STEFAN HAUSER, ANNETTE KAMINSKI, ISABELLA SYRING, STEFAN HOLDENRIEDER, KLAUS-PETER DIECKMANN, STEFAN C. MULLER, JORG ELLINGER
In Vivo Nov 2019, 33 (6) 1935-1940; DOI: 10.21873/invivo.11688
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Conclusion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

  • No related articles found.
  • PubMed
  • Google Scholar

Cited By...

  • No citing articles found.
  • Google Scholar

More in this TOC Section

  • Slowly Progressive Bone Marrow Metastasis of Gastric Cancer Followed-up Without Treatment
  • Evaluation of the Time to Onset and Outcome of Lenalidomide-induced Thrombosis and Embolism Using Spontaneous Reporting Database
  • Efficacy of Ascorbic Acid, Thiamine, and Hydrocortisone Combination Therapy: Meta-analysis of Randomized Controlled Trials
Show more Clinical Studies

Similar Articles

Keywords

  • Testicular cancer
  • biomarker
  • serum
  • MIF
  • FGF
  • HGF
  • PTN
  • ELISA
  • diagnosis
In Vivo

© 2023 In Vivo

Powered by HighWire