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Prediction of invasive placenta through cell-free RNA analysis

Research Project

Project/Area Number 20791169
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Obstetrics and gynecology
Research InstitutionShowa University

Principal Investigator

SHIHO Yoshimura  Showa University, 医学部, 普通研究生 (50384441)

Co-Investigator(Renkei-kenkyūsha) AKIHIKO Sekizawa  昭和大学, 医学部・産婦人科学教室, 准教授 (10245839)
Project Period (FY) 2008 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords癒着胎盤 / 母体血 / RNA / 妊娠高血圧症候群 / cell-free RNA / cellular RNA / 胎盤機能 / 血漿RNA / 大量出血 / 発症予知
Research Abstract

To develop the strategy predicting the invasive placenta, we have been collecting over 660 blood samples. However, since nobody have complicated with invasive placenta in the cases, we could not assess the predictive markers for invasive placenta. Therefore, we employed to predict the preeclampsia. The objective of this study is to predict occurrence of preeclampsia in a series of patients at gestational week 15-20 using a panel of cell-free or cellular mRNA markers. Data from 62 preeclamptic patients asymptomatic at the time of blood testing and 310 controls were analyzed. Multivariable analysis was performed using discriminant analysis. In the analysis of cell-free RNA, univariable analysis identified vascular endothelial growth factor receptor 1 (FLT1) as the marker with the highest detection rate, and placenta-specific-1 with the lowest. Mean estimated score for preeclampsia was 9.4 for controls and 72.5 for subjects who developed preeclampsia. An ROC curve obtained using the estimated score for preeclampsia as test variable yielded a DR of 84% (95%CI 71.8-91.5) at a 5% false-positive rate with an area under the curve of 0.927 (p<0.001). Again, DR and score for each patient for classification as preeclamptic correlated with severity. Next, in the cellular RNA analysis, the univariate ROC analysis identified soluble Flt-1 and endoglin as the markers with the highest sensitivity. The best multivariable model was obtained by combining Flt-1, Endoglin, placenta growth factor (PlGF) and parity. The relative ROC curve yielded a sensitivity of 66% at a 10% 1-specificity rate with an area under the curve of 0.884 (p<0.001). In conclusion, a panel of cell-free or cellular mRNA is able to detect subjects who will develop preeclampsia.

Report

(3 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report
  • Research Products

    (18 results)

All 2009 2008

All Journal Article (10 results) (of which Peer Reviewed: 5 results) Presentation (8 results)

  • [Journal Article] Prediction of preeclampsia by analysis of cell-free messenger RNA in maternal plasma2009

    • Author(s)
      Purwosunu Y, Sekizawa A, Okazaki S American Journal of Obstetrics, Gynecology, Farina A, Wibowo N, Nakamura M, Rizzo N, Saito H, Okai T
    • Journal Title

      American Journal of Obstetrics and Gynecology 200(4)

    • Related Report
      2009 Final Research Report
  • [Journal Article] Cellular mRNA expressions of anti-oxidant factors in the blood of preeclamptic women2009

    • Author(s)
      Nakamura M, Sekizawa A, Purwosunu Y, Okazaki S
    • Journal Title

      Prenat Diagn 29

      Pages: 691-699

    • Related Report
      2009 Final Research Report
  • [Journal Article] PP13 mRNA Expression in Trophoblasts From Preeclamptic Placentas2009

    • Author(s)
      Sekizawa A, Purwosunu Y, Yoshimura S
    • Journal Title

      Reprod Sci 16(4)

      Pages: 408-13

    • Related Report
      2009 Final Research Report
  • [Journal Article] Expression of Angiogenesis-Related Genes in the Cellular Component of the Blood of Preeclamptic Women2009

    • Author(s)
      Purwosunu Y, Sekizawa A, Yoshimura S
    • Journal Title

      Reprod Sci 16(9)

      Pages: 857-64

    • Related Report
      2009 Final Research Report
  • [Journal Article] PP13 mRNA Expression in Trophoblasts From Preeclamptic Placentas2009

    • Author(s)
      Sekizawa A, Purwosunu Y, Yoshimura S, Nakamura M, Shimizu H, Okai T, Rizzo N
    • Journal Title

      Reprod Sci 16

      Pages: 408-413

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Expression of Angiogenesis-Related Genes in the Cellular Component of the Blood of Preeclamptic Women.2009

    • Author(s)
      Purwosunu Y, Sekizawa A, Yoshimura S, Farina A, Wibowo N, Nakamura M. Shimizu H, Okaim
    • Journal Title

      Reprod Sci. 16

      Pages: 857-864

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prediction of preeclampsia by analysis of cell-free messenger RNA in maternal plasma.2009

    • Author(s)
      Purwosunu Y, Sekizawa A, Okazaki S, Farina A, Wibowo N, Nakamura M, Rizzo N, Saito H
    • Journal Title

      American Journal of Obstetrics and Gynecology 200

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cellular mRNA expressions of anti-oxidant factors in the blood of preeclamptic women.2009

    • Author(s)
      Nakamura M, Sekizawa A, Purwosunu Y, Okazaki S, Farina A, Wibowo N, Shimizu H, Okai T.
    • Journal Title

      Prenat Diagn.2009 Apr ; 29 : 691-699. 29

      Pages: 691-699

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prediction of preeclampsia by analysis of cell-free messenger RNA in maternal plasma2009

    • Author(s)
      Sekizawa A, Okazaki S, Farina A, Wibowo N, Nakamura M, et.al.
    • Journal Title

      Am J Obstet Gynecol 13-Feb(e-publish)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Evaluation of physiological alterations of the placenta through analysis of cell-free messenger ribonucleic acid concentrations of angiogenic factors2008

    • Author(s)
      Yuditiya Purwosunu, Akihiko Sekizawa, Antonio Farina, Noroyono Wibowo, Keiko Koide, Shiho Okazaki, Masamitsu Nakamura, Takashi Okai
    • Journal Title

      American Journal of Obstetrics and Gynecology 198(1)

    • Related Report
      2009 Final Research Report
  • [Presentation] 妊娠初期絨毛での酸化ストレス・血管増殖因子関連遺伝子の発現と妊娠高血圧症候群発症の関連について2009

    • Author(s)
      関沢明彦、清水華子、仲村将光、岡崎志帆、千葉博、岡井崇
    • Organizer
      第61日本産科婦人科学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2009-04-05
    • Related Report
      2009 Final Research Report
  • [Presentation] Placental protein 13遺伝子発現量と妊娠高血圧症候群発症との関連2009

    • Author(s)
      清水華子、関沢明彦、仲村将光、岡崎志帆、千葉博、岡井崇
    • Organizer
      第61日本産科婦人科学会学術集会
    • Place of Presentation
      京都
    • Year and Date
      2009-04-04
    • Related Report
      2009 Final Research Report
  • [Presentation] 妊娠高血圧症候群における母体血細胞成分中の抗酸化遺伝子発現についての検討2009

    • Author(s)
      仲村将光、関沢明彦、Yuditiya Purwosunu、岡崎志帆、千葉博、清水華子、齋藤裕、岡井崇
    • Organizer
      第12回胎児遺伝子診断研究会
    • Place of Presentation
      兵庫県
    • Year and Date
      2009-02-14
    • Related Report
      2009 Final Research Report
  • [Presentation] Placental protein 13遺伝子発現と妊娠高血圧症候群発症との関連2009

    • Author(s)
      清水華子、関沢明彦、仲村将光、岡崎志帆、千葉博、齋藤裕、岡井崇
    • Organizer
      第12回胎児遺伝子診断研究会
    • Place of Presentation
      兵庫県
    • Year and Date
      2009-02-14
    • Related Report
      2009 Final Research Report
  • [Presentation] 妊娠初期絨毛での酸化ストレス・血管増殖因子関連遺伝子の発現と妊娠高血圧症候群発症の関連について2009

    • Author(s)
      清水華子、関沢明彦、仲村将光、岡崎志帆、千葉博、岡井崇
    • Organizer
      昭和大学共同研究発表会
    • Place of Presentation
      東京
    • Related Report
      2009 Final Research Report
  • [Presentation] The mRNA expressions of anti-angiogenic factors and anti-oxidant enzymes in the cellular component of the blood from preeclamptic women2008

    • Author(s)
      Nakamura M, Sekizawa A, Purwosunu Y, Okazaki S, Shimizu H, Chiba H, Okai T
    • Organizer
      15th Congress of Federation of Asia-Oceania Perinatal Societies
    • Place of Presentation
      Nagoya
    • Year and Date
      2008-05-24
    • Related Report
      2009 Final Research Report
  • [Presentation] Symposium: Preeclampsia Prediction of preeclampsia by analysis of cell-free messenger RNA in maternal plasma2008

    • Author(s)
      Sekizawa A, Purwosunu Y, Okazaki S, Wibowo N, Nakamura M, Saito H, Okai T
    • Organizer
      15th Congress of Federation of Asia-Oceania Perinatal Societies
    • Place of Presentation
      Nagoya
    • Year and Date
      2008-05-20
    • Related Report
      2009 Final Research Report
  • [Presentation] 妊娠高血圧症候群における母体血細胞成分中の胎盤由来遺伝子の発現についての検討2008

    • Author(s)
      岡崎志帆、関沢明彦、Yuditiya Purwosunu、千葉博、仲村将光、清水華子、岡井崇
    • Organizer
      第60日本産科婦人科学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2008-04-13
    • Related Report
      2009 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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