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Part Ⅰ.Prognostic Significance Of Lymph Node Metastasis And Lymphadenectomy In Early-stage Ovarian Carcinosarcoma Part Ⅱ.Identification Of Serum Protein Biomarkers For Diagnosis And Prediction Of Chemotherapy Efficacy In Ovarian Cancer With Clin-TOF-Ⅱ-M

Posted on:2020-04-03Degree:DoctorType:Dissertation
Country:ChinaCandidate:W P WangFull Text:PDF
GTID:1364330578983572Subject:Oncology
Abstract/Summary:PDF Full Text Request
Background and Objectives:Ovarian carcinosarcoma(OCS)is an aggressive malignancy histologically composed of carcinomatous and sarcomatous elements.The role that lymph node dissection(LND)plays in the management of OCS is unclear due to its rarity.This study investigated effects of LND and LNM on survival.Methods:Data of women diagnosed with OCS,whose primary tumor was confined to ovaries(American Joint Committee on Cancer[AJCC]T1)or pelvic cavity(AJCC T2),between 1988 and 2010 were collected from the Surveillance,Epidemiology,and End Results(SEER)database.Patients were classified into lymphadenectomy(LND[+])and no lymphadenectomy(LND[-])groups.Chi-square test was used to compare the clinicopathological features of the two groups.The lymph node metastasis rates at different AJCC T stages were analyzed.Univariate and multivariate COX regression analysis were performed for all cases and cases with LND.The impacts of LND and LNM on prognosis at different AJCC T categories were analyzed by Kaplan-Meier method.The propensity score matching(PSM)was applied in order to reduce data bias between LND(+)and LND(-)groups.After PSM,the prognostic effects of lymphadenectomy were analyzed using the same statistical method as above.Results:A total of 363 women were included,of which,186 cases underwent LND and 177 cases had no LND.The prevalence of LNM was 9.6%(9/94)in AJCC Tl and 16.3%(15/92)in AJCC T2.Multivariate analysis showed that LND and AJCC T categories were independent prognostic variables,irrespective of cancer-specific survival(CSS)or overall survival(OS).Age at diagnosis was identified as an independent factor influencing OS.Subgroup analysis by AJCC T categories revealed that LND(+)group in AJCC Tlc+2a(CSS,p=0.022;OS,p=0.002)and T2(CSS,p=0.006;OS,p=0.002)had a better survival outcome compared to LND(-)group.There was no survival difference between groups in AJCC Tla+1b(CSS,p=0.286;OS,p=0.402)and T1(CSS,p=0.887;OS,p=0.582).Multivariate analysis was further carried out in LND(+)group and demonstrated that LNM and AJCC T2 had poor CSS and OS;but older age at diagnosis was associated with poor OS.Subgroup analysis by AJCC T categories showed that worse survival was observed in LNM(+)group compared to LNM(-)group in AJCC T2(CSS,p=0.004;OS,p=0.003)but not in AJCC T1(CSS,p=0.377;OS,p=0.257).PSM was made between LND(+)and LND(-)groups.After PSM,the subgroup analysis reconfirmed that patients undergoing LND had better prognosis than those without LND in AJCC Tlc+2a(CSS,p=0.025;OS,p=0.005)and T2(CSS,p=0.003;OS,p=0.001);but survival benefits were not observed in AJCC Tla+1b(CSS,p=0.313;OS,p=0.180)and T1(CSS,p=0.896;OS,p=0.951)patients undergoing LND compared to those with no LND.Conclusion:AJCC T1 and T2 categories have different LNM rates.LND can improve the prognosis of OCS patients with AJCC Tlc-2,but patients in AJCC Tla+1b have no survival benefit from LND.Background and objectives:The onset of ovarian cancer is occulted.Most of women are diagnosed as advanced cancer once found.Although initial chemotherapy is effective in 70-80%of patients with ovarian cancer,at least 20%of them are resistant to chemotherapy.In this study,Clin-time-of-flight mass spectrometry(Clin-TOF-Ⅱ-MS)combined with magnetic beads technique was used to identify peptide markers associated with diagnosis of ovarian cancer and prediction of neoadjuvant chemotherapy response.Methods:54 ovarian cancer serums and 40 healthy women serums were collected in Cancer Hospital,Chinese Academy of Medical Sciences between March 2018 and September 2018.The samples were detected using Clin-TOF-Ⅱ-MS and the serum polypeptide spectrum was obtained.Each of two groups was divided into two parts according to 1:1 ratio.The train set or test set was composed of any one part of cancer serums and any one part of normal serums.The difference feature peaks in train set are identified and verified in test set.According to the pathological evaluation for neoadjuvant chemotherapeutic response,the mild and severe chemotherapeutic response groups were divided into train set and test set as above.The difference feature peaks were identified in train set and verified in test set.Linear discriminant analysis(LDA)algorithm was used to rank the spectral peaks,and score>5 was used as the spectral peaks with statistical differences.We made ROC analysis and identified the difference peaks with AUC≥80%both in train set and test set.In train set,the best cutoff values of these differential peaks were calculated according to Youden index and applied into test set.The sensitivity and specificity of the identified peaks in diagnosing ovarian cancer and predicting chemotherapy response were not inferior to those of CA125.RESULTS:The median age of 54 patients with ovarian cancer was 55 years old.High grade serous adenocarcinoma(HGSOC)accounted for 70.4%(38/54),serous adenocarcinoma 5.6%(3/54),clear cell carcinoma 3.7%(2/54),ovarian adenocarcinoma 20.4%(11/54).FIGO Ⅲ and Ⅳ accounted for 90.7%and 9.3%,respectively.The median age of 40 healthy women was 49 years old.102 m/z in the train set were identified between ovarian cancer group and healthy group(score>5).Principal component analysis(PCA)was made in the test set using 102 m/z,which clearly distinguished the ovarian cancer group from the normal control group.Among 102 m/z,42 m/z were screened out whose AUCs in train set and test set were more than 0.8.Among 42 m/z,19 m/z expressed highly in ovarian cancer serum and 23 m/z had low expression in ovarian cancer serum.According to Youden index,the optimal cutoff values of 42 m/z in train set were calculated and verified in test set.The difference peaks in the test set were selected whose sensitivity and specificity is not inferior to CA125.The sensitivity and specificity of CA125 in diagnosis of ovarian cancer were 96.3%and 95.0%,respectively.Of 42 m/z,the sensitivity and specificity of 30 m/z in diagnosis of ovarian cancer were more than 90%.Among them,15 m/z expressed highly in ovarian cancer serum,and 15 m/z in ovarian cancer serum had low expression in ovarian cancer.71 differential peaks were identified between mild and severe chemotherapeutic reactions in the train set(score>5).The AUCs of 22 m/z in train set and test set were more than 0.8.Of them,10 m/z expressed highly in mild chemotheraputic response group and 12 m/z had high expression in severe response group.The sensitivity and specificity of CA125 for predicting chemotherapeutic response were 76.9%and 90.0%,respectively.There were 19 m/z whose sensitivity was more than 70%and specificity was more than 90%for predicting chemotherapeutic response,of which,9 had high expression in mild chemotherapy response and 10 expressed highly in severe chemotherapy response.Conclusions:With Clin-TOF-Ⅱ-MS combined with magnetic beads technique,30 difference peaks were identified between ovarian cancer and normal serum,which were of great value in the diagnosis of ovarian cancer.19 difference peaks were screened out between mild and severe chemotherapeutic response,which could effectively predict the chemotherapeutic effects.These characteristic peaks for differential diagnosis and prediction of chemotherapy efficacy are worth being further studied.
Keywords/Search Tags:ovarian carcinosarcoma, lymph node examined, lymphatic metastasis, cancer-specific survival, overall survival, ovarian cancer, circulating polypeptide, diagnosis, neoadjuvant chemotherapy efficacy
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