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Preliminary Study Of Micrornas Related To The Concurrent Chemoradiotherapy Sensitivity In Advanced Uterine Cervical Squamous Cell Carcinomas

Posted on:2013-01-12Degree:DoctorType:Dissertation
Country:ChinaCandidate:J L HuFull Text:PDF
GTID:1114330374473771Subject:Oncology
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[Background and Objiects] Cisplatin-based concurrent chemoradiotherapy is the standard treat mode of advanced uterine cervical squamous cell carcinomas (UCSCC). But in clinical practice, we found that the patients had similar clinic-pathological elements had different outcomes after concurrent chemoradiotherapy.Besides clinic-pathological elements,tumor intrinsic chemoradiotherapy sensitivity is one of the important elements for concurrent chemoradiotherapy failure in UCSCC. microRNA is a kind of small molecules RNA that playing a key role in the gene coding regulation. the correlation researches about microRNA and chemoradiotherapy sensitive in the other malignant tumor had showed the huge potiential of microRNA being tumor markers and therapeutic targets.This study aims to identify the microRNAs related to the concurrent chemoradiotherapy sensitivity in UCSCC, lay the foundation for further study of biological pathways and individual therapy.[Materials and methods] UCSCC patients in FIGO stage â…¡B to â…¢B treated with platinum based concurrent chemoradiotherapy in our hospital from April2010to April2011entered this trial. The patients were divided into chemoradiosensitive group and chemoradioresistant group respectively. Tumor tissues were obtained by biopsy before treatment and total microRNAs were extracted. TaqMan Real-time PCR microRNA Array were used to identify differentially expressed microRNAs correlated with concurrent chemoradiotherapy sensitivity between the two groups (3cases for each group), primarily selected the expression differentions of microRNAs between the two groups.Then the expression differentions of microRNAs selected in the microRNA Array were further determined by TaqMan Real-time PCR microRNA Assay in20cases (10cases for each group).[Results] TaqMan Real-time PCR microRNA Array identified170significantly differentially expressed microRNAs.One hundred and forty-four microRNAs were relatively higher expressed and26relatively lower expressed in resistant group compared with sensitive group.According to the significant statistical differences.prediction of target genes and recent studies on microRNAs and its target genes, we determined miR-101, miR-492, miR-886-3p, miR-125a-5p, miR-365and miR-489as the target microRNAs to identify the sensitive group and the resistant group for further test.Compared with sensitive group, miR-101, miR-886-3p, miR-125a-5p and miR-365showed significant high expression in resistant group,microRNA-489and miR-492showed significant low expression in resistant group.The outcome of TaqMan Real-time PCR found that miR-101and miR-492showed the same significant expression differention results between the two group with that in the microarray analysis (P<0.05and P<0.001),but other four microRNAs showed no differences between the two groups(P>0.05).[Conclusions] TaqMan Real-time PCR microRNA Array combined with Real-time PCR Assay might primarily select the microRNAs related to the concurrent chemoradiotherapy sensitivity in UCSCC.The170microRNAs selected by TaqMan Real-time PCR microRNA Array might be associated with the concurrent chemoradiotherapy sensitivity in UCSCC. The high expression of miR-101and low expression of miR-492might indicate the Chemoradioresistance in UCSCC.
Keywords/Search Tags:Cervical carcinoma, Squamous cell carcinoma, ConcurrentChemoradiotherapy, Chemoradiosenstive, Chemoradioresistant, TaqMan Real-timePCR microRNA Array, Real-time PCR
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