| ObjectiveOvarian cancer is the leading cause of death from gynecologic malignancies.Due to its lack of specific symptoms,most of patients present with advanced disease.Initial treatment consists of.cytoreductive surgery and chemotherapy.Currently,platinum-based combination chemotherapy is the standard chemotherapy regimen.Although initial response rate to chemotherapy is high,most patients unfortunately develop resistance to conventional chemotherapy by increasing disease recurrence and relapse.Therefore,chemoresistance has become a major challenge in the treatment of ovarian cancer.Most of the previous studies suggested that chemoresistance is mainly related to the mutation of the cancer cell,gene amplification and epigenetic changes.However,these studies cannot fully and accurately predict the therapeutic susceptibility of drugs.Recently,more and more studies show that the tumor microenvironment plays an equally important role in chemoresistance of malignant tumors.In addition,cancer-associated fibroblasts(CAFs)and TILs are major components in the tumor microenvironment.Our research was to investigate the expression of CAFs and TILs(CD8+T cells?CD4+T cells?FOXP3+ Treg cells)in 68 ovarian cancer patients to explore their correlation with ovarian cancer chemotherapy efficacy and prognosis.Another important purpose of our research was to provide more theoretical and predictive indicators for chemoresistance to ovarian cancer.Methods:The study retrospectively analyzed the data of 68 patients with ovarian cancer who were admitted to QiLu Hospital of Shandong University from 2003 to 2012.The clinical data such as name,age,differentiation,tumor staging,size of residual lesion,volume of ascite,lymph node metastasis,chemotherapy regimen,chemotherapy cycles,review of influencing results after chemotherapy were recorded.The PFS and OS of patients were collected by call visits.According to imaging data,the response evaluation criteria for solid tumors(RECIST)was used in the assessment of the chemotherapeutic effect.The patients were divided into complete response(CR),partial response(PR),stability(SD),and progression(PD).CR and PR groups were defined as chemotherapy-sensitive group.There was a total of 50 patients,PD was chemotherapy resistant group accounting for a total of 18 patients,there were no SD group patients.The total of 68 patients underwent cyto-reductive surgery and the diagnoses as advanced ovarian cancer(stage 3 or 4)were confirmed by the pathological outcomes.All patients received 3-8 cycles of platinum-based combination chemotherapy.The expression of a-SMA and infiltrating T cells were detected by immunohistochemistry.All Experimental statistical analyses were processed by SPSS.22 software.Results:1.The expression of a-SMA was related to the age of the patient and the size of the residual lesion.The expression of CD4+T cells in the stroma was related to the patient's age and ascite volume,while the expression of CD8+T cells?CD4+T cells?FOXP3+ Treg cells in stroma and CD8+T cells?FOXP3+ Treg cells in cancer nests were not related to age,differentiation,residual tumor size,pathological type,and ascites volume.2.The expression of CD8+T cells and CD4+T cells in the cancer nests was less than that in the stroma(p=0.001 and p=0.002).There was no significant difference in the expression of FOXP3+ Treg cells between the nests and stroma.3.The high stromal a-SMA expression accounted for 44.0%in chemosensitive patients and 72.2%in chemoresistant patients(p=0.04).The levels of CD4+T cells in cancer nests were higher in the tumors of chemosensitive patients compared with chemoresistant patients.4.The relationship between pathological factors and prognosis1)The median OS of patients younger than 55 years old was 80.2 months,while the median OS of patients older than 55 years old was only 48.2 months(p=0.017).The median PFS of patients younger than 55 years was 41.1 months,and the median PFS of patients older than 55 years was 24.4 months,but there was no statistical difference(p=0.104).2)The median OS of patients with residual lesion diameter less than 1cm was 88.5 months,and the median OS of patients with diameter greater than 1cm was 51.3 months.Statistical difference of survival was found in two groups(p=0.002).The median PFS of patients with residual lesion diameter less than 1cm was 56.4 months,which was significantly longer than those patients with a residual diameter greater than 1 cm(19.2 months)(p<0.001).3)The median OS and PFS in the chemosensitive group were 77.5months and 45.7 months,respectively,while the median OS and PFS in the chemoresistance group were 40.0 months and 10.9 months respectively.There was a significant difference between the two groups.5.The prognosis of a-SMA and infiltrating T cells on survival1)The median OS of patients with high level a-SMA was 55.3 months and the median OS of patients with low level a-SMA was 81.7 months(p=0.025).The median PFS was 26.7 months in the high-expression group which was shorter than the high-expression group,but there was no statistical difference(p=0.166).2)The median OS of patients with high CD8+/FOXP3+ Treg ratio in cancer nests was 76.8 months,which was significantly longer than those patients with low CD8+/FOXP3+Treg ratio(p=0.003).The median PFS of patients with high CD8+/FOXP3+ Treg ratio was 41.3 months,while the median PFS of patients with low CD8+/FOXP3+Treg ratio was only 20.5 months.There was a significant difference between the two groups(p=0.035).However,there was no significant correlation between stromal CD8+/FOXP3+Treg ratio and survival.3)The median OS of patients with high expression of CD8+ T cells and CD4+ T cells in cancer nests were 75.3 months and 68.7 months,respectively,while the median OS of patients with low expression were 53.7 months and 63.3 months,respectively(p=0.152 and p=0.291).There was no statistical difference between two groups.The reason for this result is mainly due to the shortage of the included sample size,and we will continue to expand the sample size to further verify the results.Conclusions:1.The stromal a-SMA expression was associated with the patients' age and the size of residual lesion.The expression of stromal CD4+ T cells was related to the age and ascite volume.2.The expression of CD8+ T cells and CD4+ T cells in the cancer nest were less than that in the stroma.3.The expression of a-SMA and CD4+ T cells in the cancer stroma were associated with the sensitivity to chemotherapy drugs.4.Age,postoperative residual size as well as chemotherapy efficacy affect the patients'overall survival and progression-free survival.5.High stromal a-SMA expression was associated with poor overall survival,while high ratio of CD8+/FOXP3+ Treg in the cancer nests was related to the improved overall survival and progression-free survival.6.The overall survival of patients with high expression of CD8+T cells and CD4+ T cells in cancer nests were longer than those patients with low expression of CD8+ T cells and CD8+ T cells,Unfortunately due to the small sample size the difference did not retain their statistical significance. |
PDF Full Text Request