Godfrey AC, Xu Z, Weinberg CR, Getts RC, Wade PA, Deroo LA, Sandler DP, Taylor JASerum microRNA expression as an early marker for breast cancer risk in prospectively collected samples from the Sister Study cohort. Breast Cancer Res 15(3): R42

Breast cancer research: BCR (Impact Factor: 5.49). 05/2013; 15(3):R42. DOI: 10.1186/bcr3428
Source: PubMed


MicroRNAs (miRNAs) are small, non-coding, single-stranded RNAs between 18-22 nucleotides long that regulate gene expression. Expression of miRNAs is altered in tumor compared to normal tissue; there is some evidence that these changes may be reflected in the serum of cancer cases compared to healthy individuals. This has yet to be examined in a prospective study where samples are collected before diagnosis.

We used Affymetrix arrays to examine serum miRNA expression profiles in 410 participants in the Sister Study, a prospective cohort study of 50,884 women. All women in the cohort had never been diagnosed with breast cancer at the time of enrollment. We compared global miRNA expression patterns in 205 women who subsequently developed breast cancer and 205 women who remained breast cancer-free. In addition within the case group we examined the association of miRNA expression in serum with different tumor characteristics, including hormone status (ER, PR, and HER-2) and lymph node status.

Overall, 414 of 1,105 of the human miRNAs on the chip were expressed above background levels in 50 or more women. When the average expression among controls was compared to cases using conditional logistic regression, 21 miRNAs were found to be differentially expressed (P≤.05). Using qRT-PCR on a small, independent sample of 5 cases and 5 controls we verified overexpression of the 3 highest expressing miRNAs among cases, miR-18a, miR-181a, and miR-222; the differences were not statistically significant in this small set. The 21 differentially expressed miRNAs are known to target at least 82 genes; using the gene list for pathway analysis we found enrichment of genes involved in cancer-related processes. In a separate case-case analyses restricted to the 21 miRNAs, we found 7 miRNAs with differential expression for women whose breast tumors differed by HER-2 expression, and 10 miRNAs with differential expression by nodal status.

miRNA levels in serum show a number of small differences between women who later develop cancer versus those who remain cancer-free.

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    • "However, while case-control studies have identified potential candidates for use as biomarkers, there have been few prospective studies investigating these. One of the few, a nested case-control study of 410 sisters of breast cancer patients, identified 21 miRNAs that were differentially expressed in serum from individuals who went on to develop cancer themselves and those who were cancer-free (Table 1) [147]. However, as the authors noted, the differences in expression were small (4–19%), which makes their use with individual patients more problematic. "
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    • "Several of the miRNAs in our 9 miRNA signature have been investigated by others. Interestingly, using prospectively collected samples from the large Sister Cohort Study, serum miR-18a was found to be expressed at higher levels in women who subsequently developed breast cancer (within 18 months from blood collection) compared to those who remained breast cancer-free, although this could not be validated in the relatively small validation set (Godfrey et al., 2013). Similar to our findings, Chan et al. found down-regulation of miR-145 in serum of women with breast cancer compared to normal controls, whereas in the same study, miR-133a and miR-143 were up-regulated, in contrast with our findings (Chan et al., 2013). "
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