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Transcript expression and genetic variability analysis of caspases in breast carcinomas suggests CASP9 as the most interesting target

  • Veronika Brynychova , Viktor Hlavac , Marie Ehrlichova , Radka Vaclavikova , Vlasta Nemcova-Furstova , Vaclav Pecha , Marketa Trnkova , Marcela Mrhalova , Roman Kodet , David Vrana , Jiri Gatek , Marie Bendova , Zdenka Vernerova , Jan Kovar and Pavel Soucek EMAIL logo
Published/Copyright: June 21, 2016
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 55 Issue 1

Abstract

Background:

Apoptosis plays a critical role in cancer cell survival and tumor development. We provide a hypothesis-generating screen for further research by exploring the expression profile and genetic variability of caspases (2, 3, 7, 8, 9, and 10) in breast carcinoma patients. This study addressed isoform-specific caspase transcript expression and genetic variability in regulatory sequences of caspases 2 and 9.

Methods:

Gene expression profiling was performed by quantitative real-time PCR in tumor and paired non-malignant tissues of two independent groups of patients. Genetic variability was determined by high resolution melting, allelic discrimination, and sequencing analysis in tumor and peripheral blood lymphocyte DNA of the patients.

Results:

CASP3 A+B and S isoforms were over-expressed in tumors of both patient groups. The CASP9 transcript was down-regulated in tumors of both groups of patients and significantly associated with expression of hormonal receptors and with the presence of rs4645978-rs2020903-rs4646034 haplotype in the CASP9 gene. Patients with a low intratumoral CASP9A/B isoform expression ratio (predicted to shift equilibrium towards anti-apoptotic isoform) subsequently treated with adjuvant chemotherapy had a significantly shorter disease-free survival than those with the high ratio (p=0.04). Inheritance of CC genotype of rs2020903 in CASP9 was associated with progesterone receptor expression in tumors (p=0.003).

Conclusions:

Genetic variability in CASP9 and expression of its splicing variants present targets for further study.

Keywords: alternative splicing; breast carcinoma; caspases; prognosis; transcript

  1. Author contributions:All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission. No writing assistance was utilized in the production of this manuscript.

  2. Research funding: This work was supported by grant of the CU Grant Agency no.: 1444313 to V.B., MH CZ – DRO (National Institute of Public Health – NIPH, 75010330) project, and grant of the Internal Grant Agency of the Czech Ministry of Health, no.: 14055-3 to P.S.

  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.

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Supplemental Material:

The online version of this article (DOI: 10.1515/cclm-2016-0271) offers supplementary material, available to authorized users.

Received: 2016-4-5
Accepted: 2016-5-17
Published Online: 2016-6-21
Published in Print: 2017-1-1

©2017 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2016-0271
Keywords for this article
alternative splicing; breast carcinoma; caspases; prognosis; transcript

Articles in the same Issue

  1. Frontmatter
  2. Editorial
  3. Describing children’s changes using clinical chemistry analytes
  4. Review
  5. Assessment of vitamin D status – a changing landscape
  6. Opinion Papers
  7. Order of blood draw: Opinion Paper by the European Federation for Clinical Chemistry and Laboratory Medicine (EFLM) Working Group for the Preanalytical Phase (WG-PRE)
  8. The principles of Health Technology Assessment in laboratory medicine
  9. Genetics and Molecular Diagnostics
  10. Functional polymorphism of lncRNA MALAT1 contributes to pulmonary arterial hypertension susceptibility in Chinese people
  11. General Clinical Chemistry and Laboratory Medicine
  12. Influence of pneumatic tube system transport on routinely assessed and spectrophotometric cerebrospinal fluid parameters
  13. Estimation of hematocrit in filter paper dried bloodspots by potassium measurement: advantage of use of perimeter ring samples over circular center sub-punch samples
  14. Evaluation of the first fully automated immunoassay method for the measurement of stimulating TSH receptor autoantibodies in Graves’ disease
  15. Comparison of four immunoassays to measure serum ferritin concentrations and iron deficiency prevalence among non-pregnant Cambodian women and Congolese children
  16. Activity and expression of dipeptidyl peptidase IV on peripheral blood mononuclear cells in patients with early steroid and disease modifying antirheumatic drugs naïve rheumatoid arthritis
  17. Hematology and Coagulation
  18. Neutrophil CD64 Index as a superior biomarker for early diagnosis of infection in febrile patients in the hematology department
  19. Dilute Russell’s viper venom time reagents in lupus anticoagulant testing: a well-considered choice
  20. Reference Values and Biological Variations
  21. Pediatric reference intervals for alkaline phosphatase
  22. Cancer Diagnostics
  23. Transcript expression and genetic variability analysis of caspases in breast carcinomas suggests CASP9 as the most interesting target
  24. CDH1 (E-cadherin) expression independently affects clinical outcome in acute myeloid leukemia with normal cytogenetics
  25. Cardiovascular Diseases
  26. Association of monocyte to HDL cholesterol level with contrast induced nephropathy in STEMI patients treated with primary PCI
  27. Low concentrations of adropin are associated with endothelial dysfunction as assessed by flow-mediated dilatation in patients with metabolic syndrome
  28. Preoperative serum potassium predicts the clinical outcome after non-cardiac surgery
  29. Diabetes
  30. A simple colorimetric assay for measuring fructosamine 3 kinase activity
  31. Acknowledgment
  32. Acknowledgment
  33. Letters to the Editor
  34. Normalisation issues in glucose measurements using phlebotomy tubes with liquid additives
  35. Utility of dilution tests in investigating interference in the free thyroxine assay
  36. Plasminogen activator inhibitor-1 as a marker of cardiovascular response in professional mountain ultra-marathon runners
  37. Pitfalls of LSD screening assays: comparison of KIMS and CEDIA immunoassays with LC-MS
  38. A two site comparison of two point-of-care activated clotting time systems
  39. Detection of the common South-East Asian β0-thalassemia mutations in samples with borderline HbA2 levels
  40. Biclonal plasma cell myeloma with the simultaneous appearance of both secretory lambda and nonsecretory kappa monoclonal light chains
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