| PART I:The Value Of Serum miRNA-206 in predicting the Chemoradiotherapy Resistance in Advanced Stage Cervical Squamous Cell Carcinoma[Background and Objectives]Cervical cancer is one of the most common malignancies in women worldwide,among which,patients of advance stage(??B)account for 60%-70%in China.Different patients response differently to CCRT.and it might attribute to differences in clinopathological factors including clinical stages.SCC-Ag before treatment,pathological type,tumor size,differentiation,pelvic lymph-nodes and so on.However,there are some patients with the same clinic-pathological factors may react totally different to the CCRT,which may be related with the inner reaction and sensitivity to treatment.miRNAs have unique advantages in tumor molecular diagnostic markers due to their specific stability and specifcity.Blood specimens are easy to obtain and convenience to clinical application.Our previous study based on serum specimen,micro RNA microarray analysis showed that 3 microRNAs expressed significantly differently between radioresistant group and radiosensitive group.This study aims at identify serum microRNAs are related to CCRT sensitivity,and lay the foundation for further study of serum tumor makers for CCRT sensitivity and potential targets for therapy.[Materias and Methods]Serum samples were collected from FIGO stage IIB to IIIB cervical squamous cell carcinoma patients treated with platinum based CCRT in our hospital during September 2013 to November 2015.Twenty well-matched samples(10 resistant and 10 sensitive)were chosen to screen the miRNA expression profile using serum samples pooled with microarrays.miRNAs expressed significantly different between two groups were further verified in 131 patients(29 resistant and 102 sensitive)serum samples with TaqMan Real-time PCR.The AUC was used to evaluate the accuracy of the biomarkers for prediction.[Results)Our earlier results showed that miR-136-5p,miR-152-3p and miR-206 were expressed significantly different between sensitive and resistant groups.Results of 8 patients preliminary verification showed that miR-136-5p and miR-152-3p could not be tested without pre-amplification reactions.Results of 131 patients verification showed that the levels of miR-206 in sensitive samples and resistant samples were 2.715±0.2115 and 14.64 ±1.184 respectively,which was significantly different(P<0.0001).Univariate analysis revealed that miR-206 expression was significantly associated with patients'DFS.Multivariate analysis demonstrated that miR-206 expression,tumor differentiation and pelvic lymph nodes metastasis were the independent prognostic factors associated with DFS in this cohort(P=0.008,0.000,0.000,respectively).The probability of the prognostic accuracy of miR-206 expression in predicting chemoradiotherapy sensitivity of ACSCC patients was 91.3%(79.3%sensitivity and 92.2%specificity).In addition,the correlation analysis of the expression level of serum miRNAs and clinicopathological factors showed that the high expression of serum miR-206 was associated with high tumor stage and big local tumor.[Conclusion]Serum miR206 overexpressed in CCRT resistant patients with advanced cervical cancer;serum miR-206 expression levels was related with prognosis of patients.These results suggest that serum miRNA-206 has the potential as new molecular marker to screen CCRT resistant patients and to give individualized treatment and prognostic prediction.PART ?Role of Positive Intraoperative Peritoneal Cytology in Early Stage Cervical Adenocarcinoma[Background and Objectives]Cervical cancer is a common gynecological malignancy,including cervical squamous cell carcinoma and cervical adenocarcinoma.Cervical adenocarcinoma was rare than cervical squamous cell carcinoma,however,in recent years the incidence shows an upward trend,accounting for about 20%of primary cervical cancer.The staging of cervical cancer is based on clinical examination,in contrast to endometrial and ovarian carcinoma,which are staged surgically.Accordingly,peritoneal cytology is not included in the International Federation of Gynecology and Obstetrics(FIGO)staging system for cervical cancer.Peritoneal washing cytology in cervical cancer was first reported in 1970.Since then,many studies have investigated the prognostic significance of peritoneal cytology in patients with cervical cancer,but the results have been inconsistent.Previous studies found that peritoneal cytology is not an important prognostic factor in patients with cervical squamous cell carcinoma.However,it might be a significant prognostic factor in patients with cervical adenocarcinoma.The aim of the present study was to investigate the prognostic role of peritoneal cytology in patients with FIGO stage IB to IIA cervical adenocarcinoma who underwent surgery,and to identify the risk factors for a positive peritoneal cytology result.[Methods]The present study included patients diagnosed with FIGO stage IB to IIA cervical adenocarcinoma who underwent surgery at our hospital,between December 1,2000,and December 31,2015.Baseline data were retrieved from patient medical records and follow-up data were collected through telephone interviews.The relationship between positive peritoneal cytology and the patients' clinicopathological features,and their prognosis was analyzed using Kaplan-Meier and Cox proportional hazards modeling.[Results]There were 136 patients who met the inclusion criteria and participated in interviews.Peritoneal cytology was positive in 13(9.6%)patients.The 5-year survival rate of patients with positive and negative cytology was 69.2%and 95.7%,respectively(P<0.001).The 3-year recurrence-free survival rate in the two groups was 76.2%and 91.3%,respectively(P=0.041).The recurrence rate was also higher in patients with positive peritoneal cytology than in those with negative peritoneal cytology.The difference was significant both for overall recurrence(P=0.002)and for local recurrence(P=0.012),but not for distant recurrence(P=0.15).Cox regression analysis showed that positive peritoneal cytology in patients with cervical adenocarcinoma was not an independent prognostic factor while pelvic lymph node involvement and parametrial involvement to be independent adverse risk factors for survival.[Conclusions]Positive peritoneal cytology in patients with cervical adenocarcinoma was associated with a poor prognosis and a higher recurrence rate,but it was not an independent prognostic factor. |
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