Do the survivin (BIRC5) splice variants modulate or add to the prognostic value of total survivin in breast cancer?

Autor: Vivianne C. G. Tjan-Heijnen, Paul N. Span, Fred C.G.J. Sweep, Jacques B. de Kok, J. J. T. M. Heuvel, John A. Foekens
Přispěvatelé: Medical Oncology
Rok vydání: 2006
Předmět:
Steroid hormone receptor
RNA Splicing
Survivin
medicine.medical_treatment
Clinical Biochemistry
Breast Neoplasms
Aetiology
screening and detection [ONCOL 5]

Biology
Disease-Free Survival
Inhibitor of Apoptosis Proteins
Breast cancer
SDG 3 - Good Health and Well-being
Predictive Value of Tests
Translational research [ONCOL 3]
medicine
Humans
RNA
Messenger

Receptor
neoplasms
Analysis of Variance
Univariate analysis
Hereditary cancer and cancer-related syndromes [ONCOL 1]
Reverse Transcriptase Polymerase Chain Reaction
Endocrinology and reproduction [UMCN 5.2]
Hormonal regulation [IGMD 6]
Biochemistry (medical)
Histology
Middle Aged
medicine.disease
Neoplasm Proteins
Steroid hormone
Genetic defects of metabolism [UMCN 5.1]
Apoptosis
Cancer research
Regression Analysis
Female
Lymph Nodes
Functional Imaging [UMCN 1.1]
Neoplasm Recurrence
Local

Microtubule-Associated Proteins
Zdroj: Clinical Chemistry, 52, 1693-700
Clinical Chemistry, 52(9), 1693-1700. American Association for Clinical Chemistry Inc.
Clinical Chemistry, 52, 9, pp. 1693-700
ISSN: 0009-9147
Popis: Background: A total of 4 additional splice variants (survivin-ΔEx3, survivin 2α, survivin-2B, and survivin-3B) have been described for survivin [baculoviral IAP repeat-containing protein (BIRC-5), approved gene symbol BIRC5], which has been implicated in both inhibition of apoptosis and regulation in mitosis in many tumor types. In this study, we assessed whether the survivin splice variants modulate or add to the prognostic value of total survivin in breast cancer. Methods: With quantitative reverse transcription-PCR, we measured mRNA concentrations of survivin and all variants in tumor tissue from 275 patients with breast cancer and associated these with clinicopathologic characteristics and relapse-free survival. Results: Total survivin, survivin-ΔEx3, and survivin 2α mRNA levels were associated with young age and ductal histology. Total survivin and survivin-ΔEx3 were highest in samples with advanced histological grade, whereas patients with 4–9 involved lymph nodes expressed less survivin-2B mRNA than those with 1–3 involved nodes. All variants were higher in tumors negative for steroid hormone receptors. Total survivin, survivin 2α, and survivin-3B were associated with poor relapse-free survival in univariate analyses. Survivin 2α and survivin-3B added to the prognostic value of total survivin in multivariate analyses. In addition, the prognostic value of total survivin was evident only in the presence of higher expression levels of these 2 variants. Conclusions: All variants of survivin exhibited particular associations with clinicopathologic characteristics (age, histology, grade, and steroid hormone receptor status) of breast cancer patients. Survival analyses suggest a modulating role of survivin 2α and survivin-3B on the biological function of total survivin.
Databáze: OpenAIRE