Startseite Uncovering the clinical impact of kallikrein-related peptidase 5 (KLK5) mRNA expression in the colorectal adenoma-carcinoma sequence
Artikel
Lizenziert
Nicht lizenziert Erfordert eine Authentifizierung

Uncovering the clinical impact of kallikrein-related peptidase 5 (KLK5) mRNA expression in the colorectal adenoma-carcinoma sequence

  • Georgia Papachristopoulou , Apostolos Malachias , Marina Devetzi , Evdoxia Kamouza ORCID logo , Andreas Scorilas ORCID logo , Dimitris Xynopoulos und Maroulio Talieri EMAIL logo
Veröffentlicht/Copyright: 13. Februar 2019
Veröffentlichen auch Sie bei De Gruyter Brill
Manuskript einreichen Informationen für Autor*innen
Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 57 Heft 8

Abstract

Background

Kallikrein-related peptidases (KLKs) are a subgroup of serine proteases located on chromosome 19q13.3. Most KLKs have been extensively studied as potential biomarkers for several carcinomas and other diseases. KLK5 was originally identified from a keratinocyte library, and its enzyme was purified from the stratum corneum of human skin. KLK5 was shown to be differentially expressed in a variety of endocrine tumors, although it is not as yet examined widely in colorectal cancer (CRC).

Methods

In this study, we quantitatively assessed the mRNA expression status of KLK5 in 197 colorectal tissues from 133 patients (70 cancerous and their paired normal colonic mucosa for 64 of them, as well as 63 colorectal adenomas) by quantitative real-time PCR (qPCR) using TaqMan probes. Statistical analysis evaluated the results.

Results

It was shown that KLK5 expression is reduced following the histologically non-cancerous-adenoma sequence (p<0.001), whereas it is increased during the sequence adenoma-carcinoma (p<0.001). Furthermore, KLK5 positive expression is associated with positive nodal status (p=0.022), advanced tumor stage (p=0.038) and high histological grade (p=0.033). Cox univariate analysis revealed that KLK5 positive expression is associated with disease-free survival (DFS) (p=0.028) and overall survival (OS) of patients (p=0.048). Kaplan-Meyer survival models showed that patients with positive KLK5 expression have lower DFS (p=0.009) and OS (p=0.019). Receiver operating characteristic (ROC) analysis demonstrated for first time that KLK5 expression had significant discriminatory values between cancer and adenoma tissues (area under the curve [AUC] 0.77; 95% confidence interval [CI]=0.69–0.85, p=0.03).

Conclusions

KLK5 mRNA expression may be useful for the differentiation of CRC from colorectal adenoma and represents a potential unfavorable prognostic biomarker for CRC.

Keywords: colon cancer; gastrointestinal cancer; molecular tumor markers; prognosis; prognostic biomarkers; quantitative real-time PCR (qPCR)
Corresponding author: Dr. Maroulio Talieri, Department of Cellular Physiology, G. Papanicolaou Research Center of Oncology, “Saint Savvas” Cancer Hospital of Athens, 171 Alexandras Avenue, 11522 Athens, Greece, Phone: +30 2106424163, Fax: +30 2106424163, E-mail:
aDeceased

Acknowledgments

This study is dedicated to the memory of Apostolos Malachias, second author of this manuscript, who has recently passed away at a very young age.

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: None declared.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin 2015;65:87–108.10.3322/caac.21262Suche in Google Scholar PubMed

2. Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, et al. Genetic alterations during colorectal-tumor development. N Engl J Med 1988;319:525–32.10.1056/NEJM198809013190901Suche in Google Scholar PubMed

3. Pietras K, Ostman A. Hallmarks of cancer: interactions with the tumor stroma. Experimental Cell Res 2010;316:1324–31.10.1016/j.yexcr.2010.02.045Suche in Google Scholar PubMed

4. Lopez-Otin C, Matrisian LM. Emerging roles of proteases in tumour suppression. Nat Rev Cancer 2007;7:800–8.10.1038/nrc2228Suche in Google Scholar PubMed

5. Yousef GM, Chang A, Scorilas A, Diamandis EP. Genomic organization of the human kallikrein gene family on chromosome 19q13.3-q13.4. Biochem Biophys Res Commun 2000;276:125–33.10.1006/bbrc.2000.3448Suche in Google Scholar PubMed

6. Borgono CA, Diamandis EP. The emerging roles of human tissue kallikreins in cancer. Nat Rev Cancer 2004;4:876–90.10.1038/nrc1474Suche in Google Scholar PubMed

7. Adamopoulos PG, Tsiakanikas P, Scorilas A. Kallikrein-related peptidases and associated microRNAs as promising prognostic biomarkers in gastrointestinal malignancies. Biol Chem 2018;399:821–36.10.1515/hsz-2017-0342Suche in Google Scholar PubMed

8. Kontos CK, Scorilas A. Kallikrein-related peptidases (KLKs): a gene family of novel cancer biomarkers. Clin Chem Lab Med 2012;50:1877–91.10.1515/cclm-2012-0247Suche in Google Scholar PubMed

9. Kontos CK, Chantzis D, Papadopoulos IN, Scorilas A. Kallikrein-related peptidase 4 (KLK4) mRNA predicts short-term relapse in colorectal adenocarcinoma patients. Cancer Lett 2013;330:106–12.10.1016/j.canlet.2012.11.036Suche in Google Scholar PubMed

10. Devetzi M, Trangas T, Scorilas A, Xynopoulos D, Talieri M. Parallel overexpression and clinical significance of kallikrein-related peptidases 7 and 14 (KLK7KLK14) in colon cancer. Thromb Haemost 2013;109:716–25.10.1160/TH12-07-0518Suche in Google Scholar PubMed

11. Alexopoulou DK, Kontos CK, Christodoulou S, Papadopoulos IN, Scorilas A. KLK11 mRNA expression predicts poor disease-free and overall survival in colorectal adenocarcinoma patients. Biomark Med 2014;8:671–85.10.2217/bmm.13.151Suche in Google Scholar PubMed

12. Christodoulou S, Alexopoulou DK, Kontos CK, Scorilas A, Papadopoulos IN. Kallikrein-related peptidase-6 (KLK6) mRNA expression is an independent prognostic tissue biomarker of poor disease-free and overall survival in colorectal adenocarcinoma. Tumour Biol 2014;35:4673–85.10.1007/s13277-014-1612-ySuche in Google Scholar PubMed

13. Kontos CK, Mavridis K, Talieri M, Scorilas A. Kallikrein-related peptidases (KLKs) in gastrointestinal cancer: mechanistic and clinical aspects. Thromb Haemost 2013;110:450–7.10.1160/TH12-11-0791Suche in Google Scholar PubMed

14. Vakrakou A, Devetzi M, Papachristopoulou G, Malachias A, Scorilas A, Xynopoulos D, et al. Kallikrein-related peptidase 6 (KLK6) expression in the progression of colon adenoma to carcinoma. Biol Chem 2014;395:1105–17.10.1515/hsz-2014-0166Suche in Google Scholar PubMed

15. Bayani J, Diamandis EP. The physiology and pathobiology of human kallikrein-related peptidase 6 (KLK6). Clin Chem Lab Med 2011;50:211–33.10.1515/cclm.2011.750Suche in Google Scholar PubMed

16. Michael IP, Sotiropoulou G, Pampalakis G, Magklara A, Ghosh M, Wasney G, et al. Biochemical and enzymatic characterization of human kallikrein 5 (hK5), a novel serine protease potentially involved in cancer progression. J Biol Chem 2005;280:14628–35.10.1074/jbc.M408132200Suche in Google Scholar PubMed

17. Brattsand M, Stefansson K, Lundh C, Haasum Y, Egelrud T. A proteolytic cascade of kallikreins in the stratum corneum. J Invest Dermatol 2005;124:198–203.10.1111/j.0022-202X.2004.23547.xSuche in Google Scholar PubMed

18. Watson AJ, Duckworth CA, Guan Y, Montrose MH. Mechanisms of epithelial cell shedding in the Mammalian intestine and maintenance of barrier function. Ann N Y Acad Sci 2009;1165:135–42.10.1111/j.1749-6632.2009.04027.xSuche in Google Scholar PubMed

19. Loktionov A. Cell exfoliation in the human colon: myth, reality and implications for colorectal cancer screening. Int J Cancer 2007;120:2281–9.10.1002/ijc.22647Suche in Google Scholar PubMed

20. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-delta delta C(T)) method. Methods 2001;25:402–8.10.1006/meth.2001.1262Suche in Google Scholar PubMed

21. Kheirelseid EA, Chang KH, Newell J, Kerin MJ, Miller N. Identification of endogenous control genes for normalisation of real-time quantitative PCR data in colorectal cancer. BMC Mol Biol 2010;11:12.10.1186/1471-2199-11-12Suche in Google Scholar PubMed PubMed Central

22. Altman DG, Lausen B, Sauerbrei W, Schumacher M. Dangers of using “optimal” cutpoints in the evaluation of prognostic factors. J Natl Cancer Inst 1994;86:829–35.10.1093/jnci/86.11.829Suche in Google Scholar PubMed

23. Shaw JL, Diamandis EP. Distribution of 15 human kallikreins in tissues and biological fluids. Clin Chem 2007;53:1423–32.10.1373/clinchem.2007.088104Suche in Google Scholar PubMed

24. Adamopoulos PG, Kontos CK, Scorilas A. Molecular cloning of novel transcripts of human kallikrein-related peptidases 5, 6, 7, 8 and 9 (KLK5 – KLK9), using Next-generation sequencing. Sci Rep 2017;7:17299.10.1038/s41598-017-16269-6Suche in Google Scholar PubMed PubMed Central

25. Kurlender L, Borgono C, Michael IP, Obiezu C, Elliott MB, Yousef GM, et al. A survey of alternative transcripts of human tissue kallikrein genes. Biochim Biophys Acta 2005;1755:1–14.10.1016/j.bbcan.2005.02.001Suche in Google Scholar PubMed

26. Adamopoulos PG, Kontos CK, Scorilas A. Identification and molecular cloning of novel transcripts of the human kallikrein-related peptidase 10 (KLK10) gene using next-generation sequencing. Biochem Biophys Res Commun 2017;487:776–81.10.1016/j.bbrc.2017.04.078Suche in Google Scholar PubMed

27. Adamopoulos PG, Kontos CK, Scorilas A. Discovery of novel transcripts of the human tissue kallikrein (KLK1) and kallikrein-related peptidase 2 (KLK2) in human cancer cells, exploiting Next-Generation Sequencing technology. Genomics 2018. pii: S0888-7543(18)30206-4. doi: 10.1016/j.ygeno.2018.03.022. [Epub ahead of print]10.1016/j.ygeno.2018.03.022Suche in Google Scholar PubMed

28. Adamopoulos PG, Kontos CK, Scorilas A. Novel splice variants of the human kallikrein-related peptidases 11 (KLK11) and 12 (KLK12), unraveled by next-generation sequencing technology. Biol Chem 2018;399:1065–71.10.1515/hsz-2017-0294Suche in Google Scholar PubMed

29. Adamopoulos PG, Kontos CK, Tsiakanikas P, Scorilas A. Identification of novel alternative splice variants of the BCL2L12 gene in human cancer cells using next-generation sequencing methodology. Cancer Lett 2016;373:119–29.10.1016/j.canlet.2016.01.019Suche in Google Scholar PubMed

30. Kontos CK, Scorilas A. Molecular cloning of novel alternatively spliced variants of BCL2L12, a new member of the BCL2 gene family, and their expression analysis in cancer cells. Gene 2012;505:153–66.10.1016/j.gene.2012.04.084Suche in Google Scholar PubMed

31. Adamopoulos PG, Kontos CK, Diamantopoulos MA, Scorilas A. Molecular cloning of novel transcripts of the adaptor-related protein complex 2 alpha 1 subunit (AP2A1) gene, using Next-Generation Sequencing. Gene 2018;678:55–6410.1016/j.gene.2018.08.008Suche in Google Scholar PubMed

32. Adamopoulos PG, Raptis GD, Kontos CK, Scorilas A. Discovery and expression analysis of novel transcripts of the human SR-related CTD-associated factor 1 (SCAF1) gene in human cancer cells using Next-Generation Sequencing. Gene 2018;670:155–65.10.1016/j.gene.2018.05.044Suche in Google Scholar PubMed

33. de Veer SJ, Furio L, Swedberg JE, Munro CA, Brattsand M, Clements JA, et al. Selective substrates and inhibitors for kallikrein-related peptidase 7 (KLK7) shed light on KLK proteolytic activity in the stratum corneum. J Invest Dermatol 2017;137:430–9.10.1016/j.jid.2016.09.017Suche in Google Scholar PubMed

34. Sidiropoulos KG, White NM, Bui A, Ding Q, Boulos P, Pampalakis G, et al. Kallikrein-related peptidase 5 induces miRNA-mediated anti-oncogenic pathways in breast cancer. Oncoscience 2014;1:709–24.10.18632/oncoscience.91Suche in Google Scholar PubMed PubMed Central

35. Pampalakis G, Obasuyi O, Papadodima O, Chatziioannou A, Zoumpourlis V, Sotiropoulou G. The KLK5 protease suppresses breast cancer by repressing the mevalonate pathway. Oncotarget 2014;5:2390–403.10.18632/oncotarget.1235Suche in Google Scholar PubMed PubMed Central

36. Jiang R, Shi Z, Johnson JJ, Liu Y, Stack MS. Kallikrein-5 promotes cleavage of desmoglein-1 and loss of cell-cell cohesion in oral squamous cell carcinoma. J Biol Chem 2011;286:9127–35.10.32469/10355/9528Suche in Google Scholar

37. Johnson JJ, Miller DL, Jiang R, Liu Y, Shi Z, Tarwater L, et al. Protease-activated receptor-2 (PAR-2)-mediated Nf-kappaB activation suppresses inflammation-associated tumor suppressor microRNAs in oral squamous cell carcinoma. J Biol Chem 2016;291:6936–45.10.1074/jbc.M115.692640Suche in Google Scholar PubMed PubMed Central

38. Chow TF, Crow M, Earle T, El-Said H, Diamandis EP, Yousef GM. Kallikreins as microRNA targets: an in silico and experimental-based analysis. Biol Chem 2008;389:731–8.10.1515/BC.2008.071Suche in Google Scholar PubMed

39. Aggarwal N, Sloane BF. Cathepsin B: multiple roles in cancer. Proteomics Clin Appl 2014;8:427–37.10.1002/prca.201300105Suche in Google Scholar PubMed PubMed Central

40. Talieri M, Li L, Zheng Y, Alexopoulou DK, Soosaipillai A, Scorilas A, et al. The use of kallikrein-related peptidases as adjuvant prognostic markers in colorectal cancer. Br J Cancer 2009;100:1659–65.10.1038/sj.bjc.6605033Suche in Google Scholar PubMed PubMed Central

41. Kerimis D, Kontos CK, Christodoulou S, Papadopoulos IN, Scorilas A. Elevated expression of miR-24-3p is a potentially adverse prognostic factor in colorectal adenocarcinoma. Clin Biochem 2017;50:285–92.10.1016/j.clinbiochem.2016.11.034Suche in Google Scholar PubMed

42. Rapti SM, Kontos CK, Papadopoulos IN, Scorilas A. Enhanced miR-182 transcription is a predictor of poor overall survival in colorectal adenocarcinoma patients. Clin Chem Lab Med 2014;52:1217–27.10.1515/cclm-2013-0950Suche in Google Scholar PubMed

43. Tsiakanikas P, Kontos CK, Kerimis D, Papadopoulos IN, Scorilas A. High microRNA-28-5p expression in colorectal adenocarcinoma predicts short-term relapse of node-negative patients and poor overall survival of patients with non-metastatic disease. Clin Chem Lab Med 2018;56:990–1000.10.1515/cclm-2017-0430Suche in Google Scholar PubMed

44. Rapti SM, Kontos CK, Papadopoulos IN, Scorilas A. High miR-96 levels in colorectal adenocarcinoma predict poor prognosis, particularly in patients without distant metastasis at the time of initial diagnosis. Tumour Biol 2016;37:11815–24.10.1007/s13277-016-5023-0Suche in Google Scholar PubMed

45. Kontos CK, Tsiakanikas P, Avgeris M, Papadopoulos IN, Scorilas A. miR-15a-5p, A novel prognostic biomarker, predicting recurrent colorectal adenocarcinoma. Mol Diagn Ther 2017;21:453–64.10.1007/s40291-017-0270-3Suche in Google Scholar PubMed

46. Rapti SM, Kontos CK, Christodoulou S, Papadopoulos IN, Scorilas A. miR-34a overexpression predicts poor prognostic outcome in colorectal adenocarcinoma, independently of clinicopathological factors with established prognostic value. Clin Biochem 2017;50:918–24.10.1016/j.clinbiochem.2017.06.004Suche in Google Scholar PubMed

47. Adamopoulos PG, Kontos CK, Rapti SM, Papadopoulos IN, Scorilas A. miR-224 overexpression is a strong and independent prognosticator of short-term relapse and poor overall survival in colorectal adenocarcinoma. Int J Oncol 2015;46:849–59.10.3892/ijo.2014.2775Suche in Google Scholar PubMed

48. Diamantopoulos MA, Kontos CK, Kerimis D, Papadopoulos IN, Scorilas A. Upregulated miR-16 expression is an independent indicator of relapse and poor overall survival of colorectal adenocarcinoma patients. Clin Chem Lab Med 2017;55: 737–47.10.1515/cclm-2016-0756Suche in Google Scholar PubMed

49. Sterlacci W, Sioulas AD, Veits L, Gonullu P, Schachschal G, GrothS, et al. 22-gauge core vs 22-gauge aspiration needle for endoscopic ultrasound-guided sampling of abdominal masses. World J Gastroenterol 2016;22:8820–30.10.3748/wjg.v22.i39.8820Suche in Google Scholar PubMed PubMed Central

50. Ferraro A, Kontos CK, Boni T, Bantounas I, Siakouli D, Kosmidou V, et al. Epigenetic regulation of miR-21 in colorectal cancer: ITGB4 as a novel miR-21 target and a three-gene network (miR-21-ITGBeta4-PDCD4) as predictor of metastatic tumor potential. Epigenetics 2014;9:129–41.10.4161/epi.26842Suche in Google Scholar PubMed PubMed Central

Received: 2018-09-13
Accepted: 2019-01-08
Published Online: 2019-02-13
Published in Print: 2019-07-26

©2019 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorials
  3. CCLM Award for the Most Cited Paper
  4. Folate and vitamin B12 assays after recalibration to the WHO International Standard 03/178: making the interpretation as simple as possible, but not simpler
  5. Reviews
  6. Blood contamination in salivary diagnostics: current methods and their limitations
  7. Central adrenal insufficiency: open issues regarding diagnosis and glucocorticoid treatment
  8. Genetics and Molecular Diagnostics
  9. Measuring the chronology of the translational process of molecular genetic discoveries
  10. Development and interlaboratory evaluation of a NIST Reference Material RM 8366 for EGFR and MET gene copy number measurements
  11. General Clinical Chemistry and Laboratory Medicine
  12. Post-translational modification-derived products are associated with frailty status in elderly subjects
  13. Urine chloride self-measurement to monitor sodium chloride intake in patients with chronic kidney disease
  14. Estimated urinary osmolality based on combined urinalysis parameters: a critical evaluation
  15. Measurement of S100B protein: evaluation of a new prototype on a bioMérieux Vidas® 3 analyzer
  16. Measuring thyroglobulin in patients with thyroglobulin autoantibodies: evaluation of the clinical impact of BRAHMS Kryptor® Tg-minirecovery test in a large series of patients with differentiated thyroid carcinoma
  17. Human chorionic gonadotropin suspected heterophile interference investigations in immunoassays: a recommended approach
  18. Certified reference material against PR3 ANCA IgG autoantibodies. From development to certification
  19. Diagnostic accuracy of a fully automated multiplex celiac disease antibody panel for serum and plasma
  20. Fasting serum bile acids concentration is associated with insulin resistance independently of diabetes status
  21. Hematology and Coagulation
  22. The association between activated protein C ratio and Factor V Leiden are gender-dependent
  23. Reference Values and Biological Variations
  24. Determination of sigma score based on biological variation for haemostasis assays: fit-for-purpose for daily practice?
  25. Calcitonin measurement in pediatrics: reference ranges are gender-dependent, validation in medullary thyroid cancer and thyroid diseases
  26. Cancer Diagnostics
  27. Uncovering the clinical impact of kallikrein-related peptidase 5 (KLK5) mRNA expression in the colorectal adenoma-carcinoma sequence
  28. Cardiovascular Diseases
  29. Performance of a novel high sensitivity cardiac troponin I assay in asymptomatic hemodialysis patients – evidence for sex-specific differences
  30. Infectious Diseases
  31. Rapid susceptibility testing of multi-drug resistant Escherichia coli and Klebsiella by glucose metabolization monitoring
  32. Letters to the Editor
  33. Vitamin B12 and folate levels in a healthy population: establishing reference intervals
  34. Reference values of a new serum folate assay traceable to the WHO International Standard
  35. Serum protein electrophoresis and complement deficiencies: a veteran but very versatile test in clinical laboratories
  36. Introduction of a novel ELISA assay for serum AMH determination
  37. Bone alkaline phosphatase on the IDS-iSYS automated analyser; cross-reactivity with intestinal ALP
  38. Evaluation of the MULTISURE HIV Rapid Test in a Korean population with low human immunodeficiency virus prevalence
  39. Vancomycin immunoassay: does the Advia Centaur XPT underestimate the exposure of patients? A method comparison study
  40. Hb Hunan and Hb Hengyang: Two unexpected discoveries during HbA1c measurements
  41. Analytical performance of a CE-marked immunoassay to quantify phosphorylated neurofilament heavy chains
  42. Implementation of an automated method for direct quantification of urinary ammonium
  43. Congress Abstracts
  44. Proceedings of ACBI 2018 41ST Annual Conference Association of Clinical Biochemists in Ireland
https://doi.org/10.1515/cclm-2018-1010
Schlagwörter für diesen Artikel
colon cancer; gastrointestinal cancer; molecular tumor markers; prognosis; prognostic biomarkers; quantitative real-time PCR (qPCR)

Artikel in diesem Heft

  1. Frontmatter
  2. Editorials
  3. CCLM Award for the Most Cited Paper
  4. Folate and vitamin B12 assays after recalibration to the WHO International Standard 03/178: making the interpretation as simple as possible, but not simpler
  5. Reviews
  6. Blood contamination in salivary diagnostics: current methods and their limitations
  7. Central adrenal insufficiency: open issues regarding diagnosis and glucocorticoid treatment
  8. Genetics and Molecular Diagnostics
  9. Measuring the chronology of the translational process of molecular genetic discoveries
  10. Development and interlaboratory evaluation of a NIST Reference Material RM 8366 for EGFR and MET gene copy number measurements
  11. General Clinical Chemistry and Laboratory Medicine
  12. Post-translational modification-derived products are associated with frailty status in elderly subjects
  13. Urine chloride self-measurement to monitor sodium chloride intake in patients with chronic kidney disease
  14. Estimated urinary osmolality based on combined urinalysis parameters: a critical evaluation
  15. Measurement of S100B protein: evaluation of a new prototype on a bioMérieux Vidas® 3 analyzer
  16. Measuring thyroglobulin in patients with thyroglobulin autoantibodies: evaluation of the clinical impact of BRAHMS Kryptor® Tg-minirecovery test in a large series of patients with differentiated thyroid carcinoma
  17. Human chorionic gonadotropin suspected heterophile interference investigations in immunoassays: a recommended approach
  18. Certified reference material against PR3 ANCA IgG autoantibodies. From development to certification
  19. Diagnostic accuracy of a fully automated multiplex celiac disease antibody panel for serum and plasma
  20. Fasting serum bile acids concentration is associated with insulin resistance independently of diabetes status
  21. Hematology and Coagulation
  22. The association between activated protein C ratio and Factor V Leiden are gender-dependent
  23. Reference Values and Biological Variations
  24. Determination of sigma score based on biological variation for haemostasis assays: fit-for-purpose for daily practice?
  25. Calcitonin measurement in pediatrics: reference ranges are gender-dependent, validation in medullary thyroid cancer and thyroid diseases
  26. Cancer Diagnostics
  27. Uncovering the clinical impact of kallikrein-related peptidase 5 (KLK5) mRNA expression in the colorectal adenoma-carcinoma sequence
  28. Cardiovascular Diseases
  29. Performance of a novel high sensitivity cardiac troponin I assay in asymptomatic hemodialysis patients – evidence for sex-specific differences
  30. Infectious Diseases
  31. Rapid susceptibility testing of multi-drug resistant Escherichia coli and Klebsiella by glucose metabolization monitoring
  32. Letters to the Editor
  33. Vitamin B12 and folate levels in a healthy population: establishing reference intervals
  34. Reference values of a new serum folate assay traceable to the WHO International Standard
  35. Serum protein electrophoresis and complement deficiencies: a veteran but very versatile test in clinical laboratories
  36. Introduction of a novel ELISA assay for serum AMH determination
  37. Bone alkaline phosphatase on the IDS-iSYS automated analyser; cross-reactivity with intestinal ALP
  38. Evaluation of the MULTISURE HIV Rapid Test in a Korean population with low human immunodeficiency virus prevalence
  39. Vancomycin immunoassay: does the Advia Centaur XPT underestimate the exposure of patients? A method comparison study
  40. Hb Hunan and Hb Hengyang: Two unexpected discoveries during HbA1c measurements
  41. Analytical performance of a CE-marked immunoassay to quantify phosphorylated neurofilament heavy chains
  42. Implementation of an automated method for direct quantification of urinary ammonium
  43. Congress Abstracts
  44. Proceedings of ACBI 2018 41ST Annual Conference Association of Clinical Biochemists in Ireland
Jetzt anmelden und 20% sparen
Institutioneller Zugang
Wie funktioniert Authentifizierung?
Haben Sie eine Idee, wie wir unsere Website verbessern können?
Bitte schreiben Sie uns.
© 2025 De Gruyter Brill
Heruntergeladen am 27.10.2025 von https://www.degruyterbrill.com/document/doi/10.1515/cclm-2018-1010/html
Button zum nach oben scrollen