RNA-Sequencing To Explore The Relationship Between IVL And UM

BackgroundIntravenous leiomyomatosis(IVL)is a smooth muscle cell tumor and uncommon to be seen in our clinical work.According to pathology,it is a benigh tumor,but it can be regarded as a malignant tumor according to its biological behavior,for it can invade into iliac vein,extend to IVL,even right atrium,or metastasize to lung,leading to fatal event.Since November 2002 to January 2015,There.were 30757 patients who were diagnosised with uterine myoma(UM)and received the treatment in the Peking Union Medical college hospital,and among these patients,there are 76 patients(0.25%)who were diagnosed with IVL.These IVL patients underwent the surgery at the cardiac surgery department、vascular department and gynecology department.In our cardiac surgery department,we carried out the surgery for 41 IVL patients from November 2002 to June 2016,and 30(73.1%)patients who received the uterine myoma surgery before,like hysterectomy or myomectomy with laparoscope.Obviously,we can hypothesize that there are some connections between IVL and UM from this interesting phenomenon.Up to now,there are two prevailing hypotheses about the pathogenesis of the IVL,exploring the relationship between IVL and UM.One theory suggests that the IVL comes from the smooth muscle cell in the vessel wall;Another theory indicates that the IVL derives from the uterine myometrium.We searched for the paper about this subject.We can get the knowledge from the paper that few studies were involved in exploring the relationship between IVL and UM from the point of molecule level during the past time,because of technology limitations.So we take advantage of RNA-sequencing,try to figure out the potential relationship between IVL and UM.Methods:Step One:We select the patients and make the specimen.All fresh tumor samples as well as paired adjacent normal tissues were obtain from patients who received the operation in Peking Union Medical College Hospital during 2014.All the patients have been diagnosed by clinician and confirmed by the two pathologists.Notably,IVL specimen were divided into three segments:the proximal,the midpiece as well as the distal.Step Two:We extract the RNA from the specimen and carry out the RNA-sequencing procedure.We pick up 50mg tissue from each sample and use the Trizol(invitrogen)to extract RNA as recommended by the manufactures’ instructions.Qualified RNA was Sequenced on the Illumina HiSeqTM 2000 platform(Illumina,San Diego,CA).Step three:Comparing those genes data between IVL and normal tissue;It is the same with UM and normal tissue,and we get the differential expressed genes,and do the analysis about their function.Then,we use the cluster analysis to make the similarity between IVL and UM clear.Results:Those DEGs from IVL and UM both have the function about the hormone stimulus,extracellular matrix,or programmed cell death and so on.And the proximal,midpiece,distal end of IVL don’t share too many DEGs,which indicates that the IVL may has heterogeneous gene expression.Conclusions:Both DEGs of IVL and uterus myoma are related to dysregulation of steroid hormone stimulus,extracellular matrix,cell adhesion and soon on.This indicate that IVL and uterus myoma may have similar dysregulated gene networks.And cluster analysis shows that all specimen cluster together.Take all these evidence into account,we may conclude that the IVL is one subtype of the UM.This study was approved by Clinical Research Ethics Committee of Peking Union Medical College Hospital.Written informed consent with signature was obtained from each patient.