Using probabilistic record linkage and propensity-score matching to identify a community-based comparison population.

In retrospective cohort studies of interventions disseminated to communities, it is challenging to find comparison groups with high-quality data for evaluation. We present one methodological approach as part of our study of birth outcomes of second-born children in a home visiting (HV) program targeting first-time mothers. We used probabilistic record linkage to link Connecticut's Nurturing Families Network (NFN) HV program and birth-certificate data for children born from 2005 to 2015. We identified two potential comparison groups: a propensity-score-matched group from the remaining birth certificate sample and eligible-but-unenrolled families. An analysis of interpregnancy interval (IPI) is presented to exemplify the approach. We identified the birth certificates of 4822 NFN families. The propensity-score-matched group had 14,219 families (3-to-1 matching) and we identified 1101 eligible-but-unenrolled families. Covariates were well balanced for the propensity-score-matched group, but poorly balanced for the eligible-but-unenrolled group. No program effect on IPI was found. By combining propensity-score matching and probabilistic record linkage, we were able to retrospectively identify relatively large comparison groups for quasi-experimental research. Using birth certificate data, we accessed outcomes for all of these individuals from a single data source. Multiple comparison groups allow us to confirm findings when each method has some limitations. Other researchers seeking community-based comparison groups could consider a similar approach.

Epithelial-to-mesenchymal transition induced by TGF-ß1 is mediated by Blimp-1-dependent repression of BMP-5.

Induction of epithelial-to-mesenchymal transition (EMT) by TGF-ß1 requires Ras signaling. We recently identified the transcriptional repressor Blimp-1 (PRDM1) as a downstream effector of the NF-κB, RelB/Bcl-2/Ras-driven pathway that promotes breast cancer cell migration. As the RelB/Blimp-1 pathway similarly required Ras signaling activation, we tested whether Blimp-1 plays a role in TGF-ß1-mediated EMT. Here, TGF-ß1 treatment of untransformed NMuMG mammary epithelial and MDA-MB-231 breast cancer cells was shown to induce Blimp-1 expression, which promoted an EMT signature and cell migration. TGFB1 and BLIMP1 RNA levels were correlated in patient breast tumors. BLIMP1 gene transcription was activated by TGF-ß1 via a c-Raf (RAF1) to AP-1 pathway. Blimp-1 induced expression of the EMT master regulator Snail (SNAI1) via repressing BMP-5, which inhibited Snail expression upon TGF-ß1 treatment. Interestingly, a similar cascade was observed during postnatal mouse mammary gland development. RelB expression was detected early in pregnancy followed progressively by Blimp-1 and then Snail; whereas, BMP-5 levels were high in nulliparous and regressing glands. Finally, lower BMP5 RNA levels were detected in patient breast tumors versus normal tissues, and correlated with cancer recurrence. Thus, the Ras effector Blimp-1 plays an essential role in TGF-ß1-induced EMT via repression of BMP-5 in breast cancer.