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Differences in microRNA expression during tumor development in the transition and peripheral zones of the prostate.

Carlsson J, Helenius G, Karlsson MG, Andrén O, Klinga-Levan K, Olsson B - BMC Cancer (2013)

Bottom Line: The t-tests revealed that the major differences in miRNA expression are found between normal and malignant tissues.Hierarchical clustering and PCA based on differentially expressed miRNAs between normal and malignant tissues showed perfect separation between samples, while the corresponding analyses based on differentially expressed miRNAs between the two zones showed several misplaced samples.A classification and cross-validation procedure confirmed these results and several potential miRNA markers were identified.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, Örebro University Hospital, Örebro, Sweden. jessica.carlsson@orebroll.se

ABSTRACT

Background: The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate.

Methods: Patients with prostate cancer were included in the study if they had a tumor with Gleason grade 3 in the PZ, the TZ, or both (n=16). Normal prostate tissue was collected from men undergoing cystoprostatectomy (n=20). The expression of 667 unique miRNAs was investigated using TaqMan low density arrays for miRNAs. Student's t-test was used in order to identify differentially expressed miRNAs, followed by hierarchical clustering and principal component analysis (PCA) to study the separation of the tissues. The ADtree algorithm was used to identify markers for classification of tissues and a cross-validation procedure was used to test the generality of the identified miRNA-based classifiers.

Results: The t-tests revealed that the major differences in miRNA expression are found between normal and malignant tissues. Hierarchical clustering and PCA based on differentially expressed miRNAs between normal and malignant tissues showed perfect separation between samples, while the corresponding analyses based on differentially expressed miRNAs between the two zones showed several misplaced samples. A classification and cross-validation procedure confirmed these results and several potential miRNA markers were identified.

Conclusions: The results of this study indicate that the major differences in the transcription program are those arising during tumor development, rather than during normal tissue development. In addition, tumors arising in the TZ have more unique differentially expressed miRNAs compared to the PZ. The results also indicate that separate miRNA expression signatures for diagnosis might be needed for tumors arising in the different zones. MicroRNA signatures that are specific for PZ and TZ tumors could also lead to more accurate prognoses, since tumors arising in the PZ tend to be more aggressive than tumors arising in the TZ.

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The number of differentially expressed miRNAs found between all combinations of sample groupings.
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Figure 2: The number of differentially expressed miRNAs found between all combinations of sample groupings.

Mentions: Student’s t-tests were performed, with and without correction for multiple testing, on all combinations of sample groupings, i.e. normal TZ tissue vs. normal PZ tissue, malignant TZ tissue vs. malignant PZ tissue, normal TZ tissue vs. malignant TZ tissue, and normal PZ tissue vs. malignant PZ tissue (for complete results see Additional files 2 and 3). The largest sets of differentially expressed genes were found in the comparisons between normal and malignant tissues (Figure 2). Between normal and malignant tissues from the TZ 149 miRNAs were found to be significantly differentially expressed (231 before applying correction for multiple testing). The same comparison in the PZ identified 65 significantly differentially expressed miRNAs (150 before correction). In contrast, only a single miRNA was significantly differentially expressed between the TZ and PZ in normal tissue (51 before correction) and none between the TZ and PZ in malignant tissue (50 before correction). Overall, these numbers clearly indicate that the main differences in miRNA expression occur between normal and malignant tissues, rather than between the prostate zones, and that these differences arise during tumor development. However, the particular miRNAs that are differentially expressed in tumor tissues vs. normal tissues may very well be different for the different zones.


Differences in microRNA expression during tumor development in the transition and peripheral zones of the prostate.

Carlsson J, Helenius G, Karlsson MG, Andrén O, Klinga-Levan K, Olsson B - BMC Cancer (2013)

The number of differentially expressed miRNAs found between all combinations of sample groupings.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3733730&req=5

Figure 2: The number of differentially expressed miRNAs found between all combinations of sample groupings.
Mentions: Student’s t-tests were performed, with and without correction for multiple testing, on all combinations of sample groupings, i.e. normal TZ tissue vs. normal PZ tissue, malignant TZ tissue vs. malignant PZ tissue, normal TZ tissue vs. malignant TZ tissue, and normal PZ tissue vs. malignant PZ tissue (for complete results see Additional files 2 and 3). The largest sets of differentially expressed genes were found in the comparisons between normal and malignant tissues (Figure 2). Between normal and malignant tissues from the TZ 149 miRNAs were found to be significantly differentially expressed (231 before applying correction for multiple testing). The same comparison in the PZ identified 65 significantly differentially expressed miRNAs (150 before correction). In contrast, only a single miRNA was significantly differentially expressed between the TZ and PZ in normal tissue (51 before correction) and none between the TZ and PZ in malignant tissue (50 before correction). Overall, these numbers clearly indicate that the main differences in miRNA expression occur between normal and malignant tissues, rather than between the prostate zones, and that these differences arise during tumor development. However, the particular miRNAs that are differentially expressed in tumor tissues vs. normal tissues may very well be different for the different zones.

Bottom Line: The t-tests revealed that the major differences in miRNA expression are found between normal and malignant tissues.Hierarchical clustering and PCA based on differentially expressed miRNAs between normal and malignant tissues showed perfect separation between samples, while the corresponding analyses based on differentially expressed miRNAs between the two zones showed several misplaced samples.A classification and cross-validation procedure confirmed these results and several potential miRNA markers were identified.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Urology, Örebro University Hospital, Örebro, Sweden. jessica.carlsson@orebroll.se

ABSTRACT

Background: The prostate is divided into three glandular zones, the peripheral zone (PZ), the transition zone (TZ), and the central zone. Most prostate tumors arise in the peripheral zone (70-75%) and in the transition zone (20-25%) while only 10% arise in the central zone. The aim of this study was to investigate if differences in miRNA expression could be a possible explanation for the difference in propensity of tumors in the zones of the prostate.

Methods: Patients with prostate cancer were included in the study if they had a tumor with Gleason grade 3 in the PZ, the TZ, or both (n=16). Normal prostate tissue was collected from men undergoing cystoprostatectomy (n=20). The expression of 667 unique miRNAs was investigated using TaqMan low density arrays for miRNAs. Student's t-test was used in order to identify differentially expressed miRNAs, followed by hierarchical clustering and principal component analysis (PCA) to study the separation of the tissues. The ADtree algorithm was used to identify markers for classification of tissues and a cross-validation procedure was used to test the generality of the identified miRNA-based classifiers.

Results: The t-tests revealed that the major differences in miRNA expression are found between normal and malignant tissues. Hierarchical clustering and PCA based on differentially expressed miRNAs between normal and malignant tissues showed perfect separation between samples, while the corresponding analyses based on differentially expressed miRNAs between the two zones showed several misplaced samples. A classification and cross-validation procedure confirmed these results and several potential miRNA markers were identified.

Conclusions: The results of this study indicate that the major differences in the transcription program are those arising during tumor development, rather than during normal tissue development. In addition, tumors arising in the TZ have more unique differentially expressed miRNAs compared to the PZ. The results also indicate that separate miRNA expression signatures for diagnosis might be needed for tumors arising in the different zones. MicroRNA signatures that are specific for PZ and TZ tumors could also lead to more accurate prognoses, since tumors arising in the PZ tend to be more aggressive than tumors arising in the TZ.

Show MeSH
Related in: MedlinePlus