Transcript levels of caspase-2 isoforms S and L in breast cancer patients


Veronika Brynychová (1, 2), Viktor Hlaváč (1, 2), Marie Ehrlichová (1), Radka Václavíková (1), Václav Pecha (3), Markéta Trnková (4), Martin Wald (5), Marcela Mrhalová (6), Kateřina Kubáčková (7), Tomáš Pikus (7), Roman Kodet (6), Jan Kovář (8), Pavel Souček (1)


  1. Toxicogenomics Unit, National Institute of Public Health in Prague, Prague
  2. Third Faculty of Medicine, Charles University, Prague
  3. Department of Oncosurgery, Medicon Inc., Prague
  4. Biolab Ltd., Prague
  5. Department of Surgery, Motol University Hospital, Prague
  6. Department of Pathology and Molecular Medicine, Motol University Hospital, Prague
  7. Department of Oncology and Radiotherapy, Motol University Hospital, Prague
  8. Department of Cell and Molecular Biology, Third Faculty of Medicine, Charles University, Prague

Caspase-2 (CASP2, OMIM: 600639) is a member of the cysteine-aspartic acid protease family involved in the apoptotic cascade. Alternative splicing of caspase-2 transcript leads to the formation of two mRNAs encoding a long caspase-2L and a short caspase-2S protein with antagonistic effects on apoptosis. An important role of caspase-2 in apoptosis induced by taxanes, used for treatment of breast cancer, was suggested. The aim of our study was to assess transcript levels of caspase-2L and S isoforms in tumor and control tissues from breast cancer patients and evaluate prognostic potential of caspase-2L, S and their ratio. Novel and specific methods for real-time PCR-based absolute quantification of caspase-2L and S transcripts were developed for this purpose.
The absolute level of caspase-2L transcript was significantly higher in tumors vs. control tissues of the general set (unselected patients, N=50, P=0.001) but not of the neoadjuvant set (neoadjuvantly treated patients, N=33). Caspase-2S transcript level did not significantly differ between tumor and control tissues in both sets. However, the caspase-2S/L transcript ratio was significantly lower in tumors compared to the controls in both sets (P=0.001). A significantly higher caspase-2S transcript level in premenopausal vs. postmenopausal patients was observed in both sets (P=0.010, P=0.043, respectively). Patients with high caspase-2S/L transcript ratio had significantly more frequently larger tumors in the general (P=0.028) but not in the neoadjuvant set. Patients with the caspase-2S/L transcript ratio above or equal the cut off had worse progression-free survival than patients with the ratio below cut off (P=0.058).
In conclusion, our data suggest that caspase-2S/L transcript ratio rather than individual transcript levels should be further studied in terms of prognosis of breast cancer patients.
This study was supported by the grant of the Czech Science Foundation, no.: GACR 301/09/0362.

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