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

Abstract

BackgroundMicroRNAs (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.MethodsA 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.ResultsMiRNA 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.ConclusionsWomen 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.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-739) contains supplementary material, which is available to authorized users.

Stat3 regulates ErbB-2 expression and co-opts ErbB-2 nuclear function to induce miR-21 expression, PDCD4 downregulation and breast cancer metastasis

“…29,30 Moreover, previous findings have found a direct correlation between miR-21 levels and the metastatic dissemination of human BC tumor samples. [31][32][33] Our findings revealed that Stat3 regulates ErbB-2 expression and co-opts its nuclear function to induce miR-21 and BC metastasis, highlighting Stat3 and NErbB-2 as novel targets to block metastatic dissemination in MErbB-2-positive BC.…”

Dysregulation and functional roles of miR-183-96-182 cluster in cancer cell proliferation, invasion and metastasis

“…The up-regulation of miR-183 is known to be associated with poor prognosis in breast cancer, colorectal cancer, hepatocellular cancer, and prostate cancer [13, 129–134], while predicts a good prognosis in osteosarcoma [135] (Table 3). This finding is consistent with its functions in cell proliferation, invasion and metastasis in these tumors types.…”

Comprehensive analysis of microRNA expression profile in malignant glioma tissues

“…Up‐regulation of miR‐494 has been demonstrated to be associated with tumor aggressiveness and metastasis in colorectal cancer, it was thus proposed as an independent prognostic marker for colorectal cancer patients (Sun et al., 2014). The same miRNA was also identified as a prognostic predictor for the minimal deviation adenocarcinoma (MDA) of uterine cervix (Lee et al., 2014) and as a risk biomarker for breast cancer development (Marino et al., 2014).…”