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Objective:To investigate the relationship between CD8 +FoxP3 +CD25 + T cell subsets and the therapeutic effect of programmed death receptor 1 (PD-1) inhibitor pembrolizumab in treatment of uterine cervical cancer. Methods:The data of 105 patients with uterine cervical cancer who received pemblizumab therapy based on chemotherapy in the First Hospital of Qinhuangdao from January 2018 to January 2020 were retrospectively analyzed. Flow cytometry was used to detect the ratio of CD8 +FoxP3 +CD25 + T cell in peripheral blood of patients. The efficacy and safety were analyzed. According to the efficacy, all patients were divided into remission group (complete remission + partial remission) and non-remission group (stable disease + progressive disease). The clinical characteristics and CD8 +FoxP3 +CD25 + T cell ratio of the two groups were compared. Multivariate logistic regression model was used to analyze the influencing factors for the efficacy. The efficacy of CD8 +FoxP3 +CD25 + T cell ratio predicting the therapeutic effect of patients was analyzed by using receiver operating characteristic (ROC) curve. Results:The objective remission rate of all patients was 17.14% (18/105), and the incidence of adverse reaction was 39.05% (41/105). The proportion of patients with a family history of cervical cancer in the remission group was lower than that than in the non-remission group [5.56% (1/18) vs. 34.48% (30/87)], and the difference was statistically significant ( χ2=6.00, P=0.014). The proportion of CD8 +FoxP3 +CD25 + T cell of 105 patients before and after treatment was (0.83±0.21)% and (0.77±0.10)%, respectively; the proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the remission group was (0.55±0.26)%, (0.31±0.12)%, respectively; the proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the non-remission group was (0.89±0.30)%, (0.87±0.28)%, respectively. The proportion of CD8 +FoxP3 +CD25 + T cell after treatment in the remission group was lower than that before treatment ( P < 0.05); there was no statistically significant difference in the proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the non-remission group ( P>0.05). The proportion of CD8 +FoxP3 +CD25 + T cell before and after treatment in the non-remission group was higher than that in the remission group (all P<0.001). The proportion of CD8 +FoxP3 +CD25 + T cell higher than the mean value of both groups before treatment and the proportion of CD8 +FoxP3 +CD25 + T cell higher than the mean value of both groups after treatment were independent risk factor of disease remission ( OR=2.542, 95% CI 1.649-3.918, P<0.001; OR=2.936, 95% CI 2.154-4.002, P<0.001). ROC curve analysis showed that the area under the curve of CD8 +FoxP3 +CD25 + T cell ratio predicting the disease remission before treatment was 0.720, and its best cut-off value was 0.77%, the senfitivity was 77.78%, the specificity was 70.11%. Conclusions:Early detection of CD8 +FoxP3 +CD25 + T cell ratio helps to predict the effect of PD-1 inhibitor pembrolizumab therapy for uterine cervical cancer.
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Objective:To investigate the clinical effect of programmed death receptor-1 (PD-1)/programmed death receptor ligand-1 (PD-L1) immunotherapy combined with concurrent radiotherapy and chemotherapy in the treatment of locally advanced cervical cancer (LACC).Methods:From November 2018 to October 2019, 51 LACC patients in Qinhuangdao First Hospital who received anti-PD-1/PD-L1 immunotherapy (pembrolizumab) combined with concurrent radiotherapy and chemotherapy [intensity modulated radiotherapy (IMRT)+ TP (taxol+ carboplatin) chemotherapy] were selected as the observation group. 51 LACC patients who received concurrent chemotherapy and radiotherapy were selected as the control group. The objective remission rate, disease control rate, tumor markers [squamous cell carcinoma antigen (SCCAg), soluble cytokeratin 19 fragment (CYFRA21-1), and carcinoembryonic antigen (CEA), carbohydrate antigen 125 (CA125)], proliferation and apoptosis indicators [survivin (Survivin), B-cell lymphoma-2 (Bcl-2), Caspase-3 (Caspase-3), apoptosis-promoting substance (Bax)], PD-1/PD-L1 [soluble PD-L1 (sPD-L1), CD4 + T cell surface PD-1 expression (PD-1 CD4 + T cells), CD8 + T cell surface PD-1 expression (PD-1 CD8 + T cell) and CD14 + monocyte surface PD-L1 expression (PD-L1 CD14 + monocyte)], safety and survival rate within 1 year were compared between the two groups. Results:(1) Disease control and safety: the objective response rate and disease control rate of the observation group were 80.39%(41/51) and 92.16%(47/51), respectively, which were higher than those of the control group by 39.22%(20/51) and 70.59%(36/51) (all P<0.05), but there was no significant difference in the incidence of side effects between the groups (all P>0.05). (2) Tumor markers and proliferation and apoptosis indexes: compared with those before treatment, the levels of serum SCCAg, CYFRA21-1, CEA, CA125, survivin and Bcl-2 in the two groups after treatment were significantly lower, and the levels of Caspase-3 and Bax were significantly higher; the above indexes in the observation group were better than those in the control group after treatment (all P<0.05). (3) PD-1/PD-L1: after treatment, sPD-L1, PD-1 CD4 + T cells, PD-1 CD8 + T cells and PD-L1 CD14 + monocytes in the observation group were significantly lower than those before treatment (all P<0.05). After treatment, the sPD-L1, PD-1 CD4 + T cells, PD-1 CD8 + T cells, PD-L1 CD14 + monocytes in the observation group were lower than those in the control group (all P<0.05). (4) Survival: the survival rate of the observation group was higher than that of the control group within 1 year ( P<0.05). Conclusions:The clinical effect of anti-PD-1/PD-L1 immunotherapy combined with concurrent radiotherapy and chemotherapy in the treatment of LACC is significant. It can effectively inhibit the progression of the disease by regulating tumor markers, proliferation and apoptosis indicators and PD-1/PD-L1 expression without increasing the risk of treatment, and has a positive effect on improving the survival rate of patients.
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Objective:To investigate the effect and mechanism of miRNA-5193 (miR-5193) on the sensitivity of cervical cancer Caski cells to cisplatin.Methods:The expression of miR-5193 in cervical cancer cell lines C33A, SiHa, Caski and normal cervical cell line Ect1/E6E7 were determined by real-time fluorescent quantitative polymerase chain reaction (qRT-PCR). Caski cells were divided into control group (no transfection, normally cultured), miR-5193-negative control (miR-NC) group (transfected with miR-NC mimic), miR-5193 group (transfected with miR-5193 mimic), miR-NC+cisplatin group (transfected with miR-NC mimic and treated with 10 μg/ml cisplatin), miR-5193+cisplatin group (transfected with miR-5193 mimic and treated with 10 μg/ml cisplatin), miR-5193+cisplatin+NC group (cotransfected with Foxp3-negative control vector and miR-5193 mimic, and treated with 10 μg/ml cisplatin), and miR-5193+cisplatin+Foxp3 group (cotransfected with Foxp3 overexpression vector and miR-5193 mimic, and treated with 10 μg/ml cisplatin). Proliferation was detected by methyl thiazolyl tetrazolium (MTT), cell cycle was detected by PI single staining method, cell apoptosis was detected by Annexin V-FITC/PI double staining method, and expressions of CDK2, p27 and C-caspase-3 proteins in cells were detected by Western blot. Bioinformatics software was used to predict miR-5193 target genes, and the luciferase reporting system was used to identify the targeting relationship.Results:The relative expression of miR-5193 in cervical cancer C33A, SiHa and Caski cells was lower than that in normal cervical Ect1/E6E7 cells (0.56±0.06, 0.41±0.03, 0.23±0.02 vs. 1.00±0.10, all P < 0.05). Compared with the control group and miR-NC group, the cell proliferation activity (absorbance value) in miR-5193, miR-NC+cisplatin and miR-5193+cisplatin groups decreased (0.58±0.06, 0.59±0.07 vs. 0.38±0.04, 0.40±0.05, 0.23±0.02, all P < 0.05), the cell apoptosis rate increased [(2.5±0.2)%, (2.7±0.3)% vs. (12.6±1.2)%, (11.9±1.5)% , (18.9±1.7)%, all P < 0.05], and the proportion of cells in G 0/G 1 phase increased [(50.4±4.2)%, (51.3±6.3)% vs. (62.3±3.2)%, (61.9±5.8)%, (71.4±5.4)%, all P < 0.05]. The expression levels of p27 and C-caspase-3 proteins increased, and the expression level of CDK2 protein decreased. The software predicted that the target gene of miR-5193 was Foxp3, which was confirmed by the luciferase reporting system. Compared with the miR-5193+cisplatin+NC group, the cell proliferation activity (absorbance value) in miR-5193+ cisplatin+Foxp3 group increased (0.24±0.03 vs. 0.65±0.05, t = 21.094, P < 0.01), the proportion of cells in G 0/G 1 phase decreased [(71.0±6.4)% vs. (60.3±4.1)%, t = 4.196, P < 0.01], the apoptosis rate of cells decreased [(19.6±1.6)% vs. (11.5±1.2)%, t = 11.880, P < 0.01], the expression levels of p27 and C-caspase-3 proteins in cells decreased, and the expression levels of CDK2 and Foxp3 proteins increased. Conclusion:The miR-5193 may increase the sensitivity of cervical cancer Caski cells to cisplatin in vitro by targeted inhibition of the Foxp3 gene.
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Objective To explore the association of COX-2 Gly587Arg polymorphism with the risk of primary liver cancer.Methods Two hundred and seventy patients with primary liver cancer and 540 health people were selected as our subjects.DNA were extracted from peripheral blood lymphocytes,and genotypes were measured by polymerase chain reaction-restriction fragment length polymorphism method.Odds ratios(OR) and 95％ confidence intervals(CI) were estimated by logistic regression.Results Two kinds of genotype (587Gly/ Gly and Gly/Arg) were found in all participants.No one carried 587Arg/Arg genotype.Among primary liver cancer patients,91.5％ (247/270,) 8.5％ (23/270) of individuals carried 587Gly/Arg and Gly/Arg genotype,which was significantly higher than that of controls (96.5％ (521/540,) 3.5％ (19/540)).Multivariate Logistic regression analysis showed that individual carried 587Gly/Arg genotype had an increased risk of developing primary liver cancer (OR =2.56,95％ CI =1.37-4.79,P =0.003) compared with 587Gly/Gly carriers.Conclusion COX-2 Gly587Arg polymorphism is a risk factor for primary liver cancer in Han.