Circulating mRNA for the PLAC1 Gene as a Second Trimester Marker (14-18 Weeks' Gestation) in the Screening for Late Preeclampsia

Abstract

Objective: To develop a model for prediction of late preeclampsia (PE; which develops at or after 34 weeks' gestation) based on maternal history and characteristics, mean arterial pressure (MAP), and circulating levels of mRNA for the placenta-specific 1 (PLAC1) gene in maternal plasma at 14-18 weeks' gestation. Method: This was a screening study of singleton pregnancies at 14-18 weeks' gestation including 43 women that subsequently developed PE and 200 that were unaffected by PE. A Gaussian model was fitted to the log distribution of the multiple of the median (log MoM) PLAC1 mRNA in the PE group and in the unaffected group. Likelihood ratios for log MoM of circulating levels of mRNA for the PLAC1 gene were used to combine the a priori risk from maternal characteristics with MAP to produce patient-specific risks for each case. Results: Screening by maternal characteristics (including BMI, woman's mother's history of PE, previous PE, and parity) (a priori risk) and MAP detected 46.8% of all cases of late PE at a fixed false-positive rate (FPR) of 10%. The addition of PLAC1 yielded a detection rate (DR) of 62.8% at the same level of FPR. PLAC1 alone yielded a DR of 30.2%. Conclusion: In late PE,molecular markers can be used to improve the DR of screening and can be a valid option for the biochemical approach.

Placental expression of PAPPA, PAPPA-2 and PLAC-1 in pregnacies is associated with FGR

“…Disruption of PLAC-1 can cause hyperplasia and FGR, whereas PLAC-1 is also reported to be one of the upregulated genes in the hyperplastic placenta generated by nuclear transfer ( 23 ). Although the association of PLAC-1 with the development of FGR during pregnancy has not been examined to date, previous studies demonstrated elevated levels of circulating PLAC-1 mRNA in preeclampsia that were directly related to the disease severity ( 24 – 26 ). In a similar manner, increased levels of PLAC-1 in the placenta of FGR-women were observed in the present study, possibly suggesting a feedback mechanism, in order to overcome the development of the disease.…”

Placenta-specific protein 1 (PLAC1) is a unique onco-fetal-placental protein and an underappreciated therapeutic target in cancer

“…Studies of the clinical preeclampsia indicators blood pressure and proteinuria also revealed significant positive correlations [16,17]. A more recent analysis of PLAC1 in maternal peripheral circulation among women who subsequently developed preeclampsia demonstrated significantly increased mRNA even in the second trimester [18]. Numerous studies have provided evidence that fetal RNAs in maternal circulation originate from trophoblast apoptosis and are, therefore, a monitor of placental health [19][20][21][22].…”

Measuring circulating placental RNAs to non-invasively assess the placental transcriptome and to predict pregnancy complications

“…Large panels of placental‐specific genes (placentally derived and representing changes in the placental transcriptome), which are dysregulated in established preeclampsia, have been identified. Reassuringly, many cpRNAs are reproducibly dysregulated across multiple studies including corticotropin‐releasing hormone, placental‐specific 1 gene, human placental lactogen (HPL) and pregnancy‐associated plasma protein‐A …”