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Prognostic relevance of glucosylceramide synthase (GCS) expression in breast cancer
Eugen Ruckhäberle1, Thomas Karn, Lars Hanker
1Department of Gynecology, J. W. Goethe-University, Frankfurt, Germany.
Purpose:
Multidrug resistance (MDR) has been linked to sphingolipid metabolism and preclinical data ascribe glucosylceramide synthase (GCS) a major role for MDR especially in breast cancer cells but no profound data are available on the expression of this potential therapeutic target in clinical breast cancer specimens.
Methods:
We analyzed microarray data of GCS expression in a large cohort of 1,681 breast tumors.
Results:
Expression of GCS was associated with a positive estrogen receptor (ER) status, lower histological grading, low Ki67 levels and ErbB2 negativity (P < 0.001 for all). In univariate analysis there was a benefit for disease free survival for patients with tumors displaying low levels of GCS expression but this significance was lost in multivariate Cox regression.
Conclusions:
Our results suggest ER positive tumors may be the most promising candidates for a potential therapeutic application of GCS inhibitors.
Insights
Glucosylceramide synthase (GCS) expression is linked to favorable breast cancer subtypes. Low GCS levels may benefit disease-free survival in estrogen receptor-positive breast cancer patients.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Multidrug resistance (MDR) is associated with sphingolipid metabolism.
- Glucosylceramide synthase (GCS) plays a key role in MDR, particularly in breast cancer cells.
- Clinical data on GCS expression in breast cancer specimens are limited.
Purpose of the Study:
- To investigate the expression of GCS in a large cohort of clinical breast cancer specimens.
- To determine the correlation between GCS expression and clinicopathological features.
- To evaluate the prognostic significance of GCS expression in breast cancer patients.
Main Methods:
- Analysis of microarray data for GCS expression in 1,681 breast tumors.
- Statistical analysis to correlate GCS expression with tumor characteristics and survival outcomes.
Main Results:
- GCS expression was associated with estrogen receptor (ER)-positive status, lower histological grade, low Ki67, and ErbB2 negativity.
- Univariate analysis indicated a survival benefit for patients with low GCS expression.
- This survival benefit was not significant in multivariate analysis.
Conclusions:
- Estrogen receptor-positive breast tumors are potential candidates for GCS inhibitor therapy.
- Further research is needed to validate the prognostic role of GCS and its therapeutic potential.