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Screening And Functional Study Of Markers For Early Diagnosis And Prognostic Evaluation Of Prostate Cancer

Posted on:2021-11-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:L WangFull Text:PDF
GTID:1484306134454994Subject:Surgery
Abstract/Summary:PDF Full Text Request
Prostate cancer is a common and multifocal disease but the diagnostic methods available are not satisfactory.Most tumors present are of low malignant potential,whereas others are highly aggressive.At present,imaging cannot be used to guide tissue biopsies safely towards the most aggressive tumor present.Puncture biopsy has a certain probability of missed diagnosis,and even if the tumor is sampled it is not known whether a more aggressive cancer is present elsewhere in the organ.To handle this problem multiple needle biopsies are taken.The biopsies often contain many normal prostate tissue,if changes in the normal tissue indicate the presence and nature of tumors,this information could be used to improve diagnostics and prognostics of prostate cancer.Current evidence that the tumor-adjacent morphologically normal prostate tissue is not completely normal is reviewed,and its molecular level has changed,with the potential to be used to diagnose prostate cancer.In this study,the prostate basal epithelial cells and luminal epithelial cell subsets were isolated and purified by primary cell culture after pathological identification of normal prostate tissue and morphologically normal tissue surrounding tumor.Transcriptome sequencing analysis was carried out respectively,which largely excluded the interference of other types of cells and improved the reliability of sequencing results.Through a series of screening,some of the differential genes were locked for subsequent studies,and the differential genes were functionally analyzed.According to Epstein's criteria,peripheral morphologically normal tissues derived from the of inert and invasive prostate cancer were grouped,and two cell subsets of the prostate were sequenced to screen differential genes and perform a series of functional enrichment analyses.Analysis of sequencing data revealed significant differences in the expression of TACC3 gene in normal tissues of the prostate and morphologically normal tissue surrounding normal,so we further investigated whether TACC3 plays an important role in prostate cancer progression.TACC3 has recently been considered to be an important factor in regulating the growth and differentiation of many human tumor cells.This study illustrated the important role of TACC3 in primary cilia formationand tumor growth.For the knock-down of TACC3 gene,in vitro and in vivo experiments have a significant inhibitory effect on prostate cancer cell growth.Furthermore,we found TACC3 involved in cilia formation as a microtubule-associated protein.TACC3 can interfere with filamin A-meckelin interactions and thus inhibit primary cilia production.Hence,targeting TACC3 and its associated molecules may become a novel approach for prostate cancer therapy.
Keywords/Search Tags:PCa, Early diagnosis, Primary cilia, TACC3, Meckelin filamin A
PDF Full Text Request
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