1.The expression changes and clinical significance of serum microRNA-155 and 135b-5p in patients with peptic ulcer complicated with Helicobacter pylori infection
Kuankuan AI ; Ruirui HU ; Yuan XUE ; Yan WANG
Chinese Journal of Postgraduates of Medicine 2024;47(3):237-241
Objective:To investigate the expression levels and clinical significance of serum microRNA (miR) -155 and miR-135b-5p in patients with peptic ulcer complicated with Helicobacter pylori ( Hp) infection. Methods:A prospective study was conducted, and 263 patients with peptic ulcer were selected consecutively from July 2021 to February 2023 at the Affiliated Hospital of Jining Medical College. Among them, 146 cases were confirmed as Hp infection ( Hp infection group) and 117 cases were not complicated with Hp infection (non Hp infection group) by 14C breath test; type Ⅰ Hp infection was in 110 cases, and type Ⅱ Hp infection was in 36 cases by immunoblotting method. The serum expression levels of miR-155 and miR-135b-5p were detected by real-time fluorescence quantitative polymerase chain reaction, serum gastrin level was detected by radioimmunoassay method, and the serum pepsinogen (PG) Ⅰ and PG Ⅱ were detected by enzyme linked immunosorbent assay. The clinical data were recorded. Multivariate Logistic regression analysis was used to analyze the independent risk factors of Hp infection in patients with peptic ulcer; receiver operating characteristic (ROC) curve was used to analyze the efficacy of serum miR-155 and miR-135b-5p in diagnosis the Hp infection in patients with peptic ulcer. Results:The gastrin, PG Ⅰ, PG Ⅱ, ulcer bleeding rate and recurrence rate in Hp infection group were significantly higher than those in non Hp infection group: (108.47 ± 15.35) ng/L vs. (79.63 ± 10.58) ng/L, (295.41 ± 37.26) pg/L vs. (236.75 ± 29.17) pg/L, (44.08 ± 8.52) pg/L vs. (39.29 ± 6.74) pg/L, 25.34% (37/146) vs. 15.38% (18/117) and 21.92% (32/146) vs. 11.97% (14/117), and there were statistical differences ( P<0.01 or <0.05). The serum miR-155 and miR-135b-5p in Hp infection group were significantly higher than those in non Hp infection group (1.94 ± 0.63 vs. 0.95 ± 0.29 and 1.86 ± 0.57 vs. 1.03 ± 0.31), and there were statistical differences ( P<0.01). The serum miR-155 and miR-135b-5p in patients with typeⅠ Hp infection were significantly higher than those in patients with type Ⅱ Hp infection (2.05 ± 0.66 vs. 1.60 ± 0.54 and 1.97 ± 0.61 vs. 1.52 ± 0.45), and there were statistical differences ( P<0.01). Multivariate Logistic regression analysis result showed that serum miR-155, miR-135b-5p, gastrin and PG Ⅰwere independent risk factors of Hp infection in patients with peptic ulcer ( OR = 1.443, 1.436, 1.452 and 1.438; 95% CI 1.165 to 1.787, 1.146 to 1.799, 1.187 to 1.777 and 1.150 to 1.798; P<0.01). ROC curve analysis result showed that the area under the curve of serum miR-155 combined with miR-135b-5p in the diagnosis of Hp infection in patients with peptic ulcer was significantly greater than that of serum miR-155 and miR-135b-5p alone (0.907 vs. 0.839 and 0.836, Z = 2.57 and 2.81, P = 0.010 and 0.005). Conclusions:The serum levels of miR-155 and miR-135b-5p are high in patients with peptic ulcer complicated with Hp infection, and the combination of the two has high diagnostic value for Hp infection in patients with peptic ulcer.
2.Study on the expression of ADAR1 and AZIN1 in cancer tissues and adjacent tissues of gastric cancer patients and their clinical significance
Yuan XUE ; Hui LI ; Kuankuan AI ; Zhen XU ; Chengjiu HU
Chinese Journal of Endocrine Surgery 2024;18(3):418-422
Objective:To explore the expression of ADAR1 and AZIN1 in cancer tissues and adjacent tissues of gastric cancer patients and study their clinical significance.Methods:116 patients with stage I-III gastric cancer treated in the Department of Gastroenterology and Oncology from Jan. 2020 to Jan. 2021 were recruited as research subjects. All patients were treated with surgical resection and confirmed by histopathological analysis. All patients signed the protocol informed consent upon inclusion in the study. The relationship between ADAR1 and AZIN1 expression and clinicopathological characteristics in gastric cancer tissues of patients was analyzed. The expression of ADAR1 and AZIN1 mRNA in gastric cancer and adjacent tissues was analyzed by qPCR. The expression of ADAR1 and AZIN1 in gastric cancer and adjacent tissues was analyzed by immunohistochemistry. The relationship between ADAR1, AZIN1 and patient survival rate 3 years after surgery was analyzed. Multivariable Logistic regression was used to analyze factors affecting the poor prognosis of gastric cancer patients. ROC curve was used to analyze the diagnostic performance of ADAR1 and AZIN1 expression levels in the prognosis of gastric cancer patients.Results:ADAR1 and AZIN1 had higher expression levels in undifferentiated gastric cancer tissue, patients with lymph node metastasis, and higher TNM staging, indicating that the high expression of these two genes was closely related to the malignancy of gastric cancer. QPCR analysis showed that the expression of ADAR1 mRNA in gastric cancer tissue and adjacent tissue was 1.96 ± 0.18 and 1.12 ± 0.03, respectively. The expression of AZIN1 mRNA in gastric cancer tissue and adjacent tissue was 1.85 ± 0.16 and 1.04 ± 0.02, respectively. The expression of ADAR1 mRNA in gastric cancer tissue was higher than that in adjacent tissue ( P<0.05). ADAR1 and AZIN1 positive patients were associated with lower 3-year survival rates ( P<0.05). In the multivariate logistic regression analysis of poor prognosis in gastric cancer patients, low differentiation, deepening of infiltration, lymph node metastasis, higher TNM staging, positive expression of ADAR1 and AZIN1 all significantly increased the risk of poor prognosis in gastric cancer ( P<0.05). The sensitivity and AUC value of joint detection were higher than those of ADAR1 and AZIN1 alone detection ( P<0.05) . Conclusions:The expression of ADAR1 and AZIN1 in gastric cancer tissues is significantly higher than that in para-cancerous tissues, especially in patients with undifferentiated tumors, lymph node metastasis and high TNM stage. The high expression of these two genes is closely related to the poor prognosis of gastric cancer patients, and the combined detection shows higher diagnostic efficiency. Therefore, ADAR1 and AZIN1, as key biomarkers for the development and prognosis of gastric cancer, provide new targets for gastric cancer treatment.
3.Clinical mechanism of PD-1 and VEGFR2 inhibitors combined to interfere with the progression of colon cancer liver metastasis
Kuankuan AI ; Feng YANG ; Yaowen ZHANG
Chinese Journal of Endocrine Surgery 2024;18(4):573-577
Objective:To explore the clinical mechanism of PD-1 and VEGFR2 inhibitors combined in intervening the progression of colon cancer liver metastasis.Methods:120 patients with colon cancer liver metastasis from Feb. 2021 to Dec. 2022 were selected as research subjects. According to the treatment plan, patients were divided into control group ( n=60) and observation group ( n=60). The control group received PD-1 inhibitor treatment, while the observation group received combination of PD-1 inhibitor and VEGFR2 inhibitor treatment. Tumor vascular density and permeability were evaluated by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The expression of PD-1 and VEGFR2 proteins were analyzed through protein blot. The levels of serum inflammatory factors IFN - γ, TNF - α, and IL-12 in patients before and after intervention were detected using ELISA. The tumor control effects between the two groups of patients were compared. The average overall survival and average progression free survival between the two groups of patients were compared. Results:Before intervention, there was no statistically significant difference in vascular permeability or density between the observation group and the control group patients; After 6 weeks of intervention, the vascular permeability and density of patients in the observation group decreased compared to the control group. There were no significant changes in vascular permeability or density in the control group before and after intervention. Before intervention, there was no statistically significant difference in the expression of PD-1 or VEGFR2 proteins between the observation group and the control group; P>0.05; After 6 weeks of intervention, the expression of PD-1 and VEGFR2 proteins in both groups of patients decreased compared to that before intervention. The expression of PD-1 and VEGFR2 proteins in the observation group decreased compared to that of the control group (PD-1: 1.04±0.02 vs. 1.30±0.04; VEGFR2: 1.12±0.01 vs. 1.57±0.16) ; P<0.05. Before intervention, there was no statistically significant difference in serum levels of IFN - γ, TNF - α, or IL-12 between the observation group and the control group; After 6 weeks of intervention, the serum levels of IFN - γ, TNF - α, and IL-12 in both groups of patients increased compared to those before intervention. However, the observation group showed a more significant increase in IFN - γ, TNF - α, and IL-12 levels compared to the control group (IFN - γ: 38.44±3.28 pg/mL vs. 27.55±2.63 pg/mL; TNF - α: 44.62±2.15 pg/mL vs. 30.57±2.09 pg/mL) ; IL-12: 33.49±2.51 pg/mL vs. 20.75±1.86 pg/mL; P<0.05). In the control group, there were 8 cases of partial tumor remission, 14 cases of stable tumor phase, and 22 cases of effective tumor control. In the observation group, there were 17 cases of partial tumor remission, 24 cases of stable tumor phase, and 41 cases of effective tumor control. PR, SD, and DCR in the observation group were higher than those in the control group, and the difference was statistically significant ( P<0.05). The average overall survival and mean progression free survival of the observation group were longer than those of the control group. Conclusions:Combined treatment with PD-1 and VEGFR2 inhibitors significantly improves tumor control and survival in patients with colon cancer liver metastases. By reducing tumor vessel density and permeability, enhancing immune responses, and reducing immune evasion of tumor cells, the combined intervention provides a more effective clinical strategy for the treatment of colon cancer liver metastases.