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MicroRNA expression as risk biomarker of breast cancer metastasis: a pilot retrospective case-cohort study.

Marino AL, Evangelista AF, Vieira RA, Macedo T, Kerr LM, Abrahão-Machado LF, Longatto-Filho A, Silveira HC, Marques MM - BMC Cancer (2014)

Bottom Line: Furthermore, metastatic miRNAs shared across all clinical stages did not present high sensitivity and specificity when compared to specific-CS miRNAs.Between them, hsa-miR-183 was the most significative of CSII, which miRNAs combination for CSII (hsa-miR-494, hsa-miR-183 and hsa-miR-21) was significant and were a more effective risk marker compared to the single miRNAs.Women with metastatic breast cancer, especially CSII, presented up-regulated levels of miR-183, miR-494 and miR-21, which were associated with a poor prognosis.

View Article: PubMed Central - PubMed

Affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, Brazil. mmcmsilveira@gmail.com.

ABSTRACT

Background: MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in post-transcriptional gene regulation and have recently been shown to play a role in cancer metastasis. In solid tumors, especially breast cancer, alterations in miRNA expression contribute to cancer pathogenesis, including metastasis. Considering the emerging role of miRNAs in metastasis, the identification of predictive markers is necessary to further the understanding of stage-specific breast cancer development. This is a retrospective analysis that aimed to identify molecular biomarkers related to distant breast cancer metastasis development.

Methods: A retrospective case cohort study was performed in 64 breast cancer patients treated during the period from 1998-2001. The case group (n = 29) consisted of patients with a poor prognosis who presented with breast cancer recurrence or metastasis during follow up. The control group (n = 35) consisted of patients with a good prognosis who did not develop breast cancer recurrence or metastasis. These patient groups were stratified according to TNM clinical stage (CS) I, II and III, and the main clinical features of the patients were homogeneous. MicroRNA profiling was performed and biomarkers related to metastatic were identified independent of clinical stage. Finally, a hazard risk analysis of these biomarkers was performed to evaluate their relation to metastatic potential.

Results: MiRNA expression profiling identified several miRNAs that were both specific and shared across all clinical stages (p ≤ 0.05). Among these, we identified miRNAs previously associated with cell motility (let-7 family) and distant metastasis (hsa-miR-21). In addition, hsa-miR-494 and hsa-miR-21 were deregulated in metastatic cases of CSI and CSII. Furthermore, metastatic miRNAs shared across all clinical stages did not present high sensitivity and specificity when compared to specific-CS miRNAs. Between them, hsa-miR-183 was the most significative of CSII, which miRNAs combination for CSII (hsa-miR-494, hsa-miR-183 and hsa-miR-21) was significant and were a more effective risk marker compared to the single miRNAs.

Conclusions: Women with metastatic breast cancer, especially CSII, presented up-regulated levels of miR-183, miR-494 and miR-21, which were associated with a poor prognosis. These miRNAs therefore represent new risk biomarkers of breast cancer metastasis and may be useful for future targeted therapies.

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Related in: MedlinePlus

Heatmaps of the best biomarkers stratified according to clinical stage. Figure 1A shows non-metastatic vs. metastatic patients in CSI, Figure 1B shows patients in CSII, and Figure 1C shows patients in CSIII.
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Fig1: Heatmaps of the best biomarkers stratified according to clinical stage. Figure 1A shows non-metastatic vs. metastatic patients in CSI, Figure 1B shows patients in CSII, and Figure 1C shows patients in CSIII.

Mentions: The differentially expressed miRNAs (non-metastatic vs. metastatic groups) stratified according to clinical stage (CSI, CSII and CSIII) are shown in Additional file2: Figure S1. The optimal biomarkers were ranked according to sensitivity and specificity values ≥ 80%. The clusters resulting from this analysis are represented in Figure 1, revealing miRNAs highly specific for the metastatic process. The miRNA hsa-miR-183 (CSII) was also selected for further analysis.


MicroRNA expression as risk biomarker of breast cancer metastasis: a pilot retrospective case-cohort study.

Marino AL, Evangelista AF, Vieira RA, Macedo T, Kerr LM, Abrahão-Machado LF, Longatto-Filho A, Silveira HC, Marques MM - BMC Cancer (2014)

Heatmaps of the best biomarkers stratified according to clinical stage. Figure 1A shows non-metastatic vs. metastatic patients in CSI, Figure 1B shows patients in CSII, and Figure 1C shows patients in CSIII.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4195914&req=5

Fig1: Heatmaps of the best biomarkers stratified according to clinical stage. Figure 1A shows non-metastatic vs. metastatic patients in CSI, Figure 1B shows patients in CSII, and Figure 1C shows patients in CSIII.
Mentions: The differentially expressed miRNAs (non-metastatic vs. metastatic groups) stratified according to clinical stage (CSI, CSII and CSIII) are shown in Additional file2: Figure S1. The optimal biomarkers were ranked according to sensitivity and specificity values ≥ 80%. The clusters resulting from this analysis are represented in Figure 1, revealing miRNAs highly specific for the metastatic process. The miRNA hsa-miR-183 (CSII) was also selected for further analysis.

Bottom Line: Furthermore, metastatic miRNAs shared across all clinical stages did not present high sensitivity and specificity when compared to specific-CS miRNAs.Between them, hsa-miR-183 was the most significative of CSII, which miRNAs combination for CSII (hsa-miR-494, hsa-miR-183 and hsa-miR-21) was significant and were a more effective risk marker compared to the single miRNAs.Women with metastatic breast cancer, especially CSII, presented up-regulated levels of miR-183, miR-494 and miR-21, which were associated with a poor prognosis.

View Article: PubMed Central - PubMed

Affiliation: Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos 14784-400, Brazil. mmcmsilveira@gmail.com.

ABSTRACT

Background: MicroRNAs (miRNAs) are small, non-coding RNA molecules involved in post-transcriptional gene regulation and have recently been shown to play a role in cancer metastasis. In solid tumors, especially breast cancer, alterations in miRNA expression contribute to cancer pathogenesis, including metastasis. Considering the emerging role of miRNAs in metastasis, the identification of predictive markers is necessary to further the understanding of stage-specific breast cancer development. This is a retrospective analysis that aimed to identify molecular biomarkers related to distant breast cancer metastasis development.

Methods: A retrospective case cohort study was performed in 64 breast cancer patients treated during the period from 1998-2001. The case group (n = 29) consisted of patients with a poor prognosis who presented with breast cancer recurrence or metastasis during follow up. The control group (n = 35) consisted of patients with a good prognosis who did not develop breast cancer recurrence or metastasis. These patient groups were stratified according to TNM clinical stage (CS) I, II and III, and the main clinical features of the patients were homogeneous. MicroRNA profiling was performed and biomarkers related to metastatic were identified independent of clinical stage. Finally, a hazard risk analysis of these biomarkers was performed to evaluate their relation to metastatic potential.

Results: MiRNA expression profiling identified several miRNAs that were both specific and shared across all clinical stages (p ≤ 0.05). Among these, we identified miRNAs previously associated with cell motility (let-7 family) and distant metastasis (hsa-miR-21). In addition, hsa-miR-494 and hsa-miR-21 were deregulated in metastatic cases of CSI and CSII. Furthermore, metastatic miRNAs shared across all clinical stages did not present high sensitivity and specificity when compared to specific-CS miRNAs. Between them, hsa-miR-183 was the most significative of CSII, which miRNAs combination for CSII (hsa-miR-494, hsa-miR-183 and hsa-miR-21) was significant and were a more effective risk marker compared to the single miRNAs.

Conclusions: Women with metastatic breast cancer, especially CSII, presented up-regulated levels of miR-183, miR-494 and miR-21, which were associated with a poor prognosis. These miRNAs therefore represent new risk biomarkers of breast cancer metastasis and may be useful for future targeted therapies.

Show MeSH
Related in: MedlinePlus