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Effect of HIPEC assisted tirelizumab on immune function and tumor marker levels in patients with advanced gastric cancer
Author:Sun Guohui Abudula Abudiaini Aerhenbeike Tuerbai Mulati Kuerban Bumaireyimu Yibureyimn
keyword: Gastric cancer,advanced stage; Hyperthermic intraperitoneal chemotherapy; Tirelizumab; Immune function; Tumor biomarker;
Objective To investigate the effects of hyperthermic intraperitoneal chemotherapy(HIPEC) assisted with tirelizumab on immune function, tumor markers, tumor invasion-related indicators, quality of life and clinical efficacy in patients with advanced gastric cancer. Methods Eighty-six patients with advanced gastric cancer treated in the hospital from January 2022 to February 2023 were randomly divided into conventional chemotherapy group(n=43) and combination therapy group(n=43). Conventional chemotherapy group was given conventional FOLFOX chemotherapy regimen, and combination treatment group was given HIPEC chemotherapy regimen and intraperitoneal tirelizumab injection on the basis of FOLFOX chemotherapy regimen. The clinical efficacy, quality of life(KPS), expression levels of immune function(CD4+T cell ratio, CD8+T cell ratio, CD4+/CD8+ ratio), tumor markers[carcinoembryonic antigen(CEA), carbohydrate antigen 125(CA125), carbohydrate antigen 19-9(CA19-9)] and tumor invasion-related markers [vascular endothelial growth factor(VEGF), basic fibroblast growth factor(bFGF), matrix metalloproteinase-2(MMP-2)] were compared between the two groups before and 6 months after treatment. Results The DCR of combined chemotherapy group was 69.77%, significantly higher than that of conventional chemotherapy group(46.51%, χ2/P=3.842/0.050). After 6 months of treatment, the CD4+T cell ratio and CD4+/CD8+ ratio in the combined therapy group were significantly higher than those in the conventional chemotherapy group, while the CD8+T cell ratio was significantly lower than those in the conventional chemotherapy group(t/P=4.135/<0.001, 2.980/0.004, 3.864/<0.001). CEA and CA125 levels were significantly lower than those before treatment and in conventional chemotherapy group(t/P=5.926/<0.001, ca19-9="" level="" had="" no="" significant="" difference="" between="" the="" two="" p="">0.05). The levels of VEGF, bFGF and MMP-2 decreased in both groups, and the average levels of VEGF and MMP-2 in the combined treatment group were lower than those in the conventional chemotherapy group(t/P=2.513/0.014,2.390/0.019), but there was no significant difference in the level of bFGF between the two groups(P>0.05). The average KPS score of the two groups increased successively after 3 and 6 months of treatment, and the level of KPS in the combined treatment group was higher than that in the conventional chemotherapy group(P<0.05). Conclusion Compared with the traditional chemotherapy regimen, HIPEC chemotherapy combined with tirelizumab can significantly improve the immune function of patients with advanced gastric cancer and reduce the levels of tumor markers and tumor invasion-related indexes, which is helpful to improve the clinical efficacy and quality of life of patients.
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The expression of DDX24, TRIP12 expression in hepatocellular carcinoma and correlation with epithelial mesenchymal transition and clinical prognosis
Author:Jing Lijun Zhang Min Wei Xue Tang Yubin
keyword: Hepatocellular carcinoma; DEAD cassette helicase 24; Thyroid hormone receptor interacting factor 12; Epithelial mesenchymal transition; Clinical prognosis;
Objective To investigate the expression of DEAD-box helicase 24(DDX24) and thyroid hormone receptor interactor 12(TRIP12) in hepatocellular carcinoma(HCC), and analyze their relationship with epithelial mesenchymal transition(EMT) and clinical prognosis.Methods A retrospective selection was conducted on 96 HCC patients who underwent liver and gallbladder surgery at the 940 Hospital of the Chinese People's Liberation Army Joint Logistics Support Force from February 2019 to January 2021. The expressions of DDX24 and TRIP12 proteins were detected by immunohistochemistry. The expressions of DDX24 mRNA, TRIP12 mRNA and EMT markers E-cadherin(E-cad) mRNA, N-cadherin(N-cad) mRNA and TWIST mRNA were detected by real-time fluorescence quantitative PCR. Pearson correlation analysis was used to analyze the correlation between DDX24 mRNA, TRIP12 mRNA and EMT indicators. Kaplan-Meier curve was drawn, and Log-Rank test was used to analyze the difference in prognosis of HCC patients between DDX24 mRNA and TRIP12 mRNA high expression group and low expression group. Multivariate Cox proportional hazards model was used to analyze the independent factors affecting the prognosis of HCC patients. Results The positive rates of DDX24 and TRIP12 in HCC cancer tissues were higher than those in adjacent tissues(χ2/P=109.714/<0.001, 108.755/<0.001). Compared with adjacent tissues, the expressions of DDX24 mRNA, TRIP12 mRNA, N-cad mRNA and TWIST mRNA in HCC cancer tissues were higher, and E-cad mRNA was lower, and the differences were statistically significant(t/P=35.810/<0.001, 48.036/<0.001, 25.015/<0.001, 48.482/<0.001, 38.069/<0.001). DDX24 mRNA expression was positively correlated with TRIP12 mRNA expression in HCC tissues(r=0.701, P<0.001). DDX24 mRNA and TRIP12 mRNA were positively correlated with N-cad mRNA and TWIST mRNA, and negatively correlated with E-cad mRNA(r/P=0.723/<0.001, 0.661/<0.001, 0.706/<0.001,0.745/<0.001,-0.694/<0.001,-0.609/<0.001). DDX24 mRNA and TRIP12 mRNA in HCC tissues of CNLC stage Ⅱ-Ⅲ, poor differentiation and no vascular invasion were higher than those in CNLC stage I and moderately and highly differentiated and vascular invasion(DDX24:t/P=10.348/<0.001,18.474/<0.001,6.302/<0.001;TRIP12:t/P=25.661/<0.001, 36.396/<0.001,14.928/<0.001). The 3-year overall survival rates of DDX24 mRNA high expression group and low expression group were 39.13%(18/46) and 64.00%(32/50), respectively. There was a significant difference in the overall survival curve between the two groups(Log rank χ2=7.491, P=0.006). The 3-year overall survival rates of TRIP12 mRNA high expression group and low expression group were 36.17%(17/47) and 67.35%(33/49), respectively. There was a significant difference in the overall survival curve between the two groups(Log rank χ2=8.146, P=0.004). CNLC stage Ⅱ-Ⅲ, poor differentiation, vascular invasion, high expression of DDX24 mRNA, and high expression of TRIP12 mRNA were risk factors for the death and prognosis of HCC patients[HR(95%CI)=1.611(1.175-2.209), 1.768(1.238-2.526), 1.464(1.089-1.968), 1.859(1.330-2.599), 1.775(1.275-2.473)].Conclusion DDX24 and TRIP12 are up-regulated in HCC, which are correlated with EMT markers, CNLC stage Ⅱ-Ⅲ, degree of differentiation and vascular invasion. Both of them are helpful to evaluate the prognosis of HCC patients.
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Observation on the therapeutic effect of PD-1 antibody combined with thymosin α1 and HAIC in treating primary liver cancer with portal vein thrombosis
Author:Chen Wusheng Jia Zhiqiang Ma Liwei Liu Qiong Duan Yusong
keyword: Primary liver cancer; Portal vein tumor thrombus; PD-1 antibody; Thymosin α1; Hepatic arterial perfusion chemotherapy; Therapeutic effect;
Objective To investigate the therapeutic effect of programmed death-1(PD-1) antibody combined with thymosin α1 and hepatic arterial infusion chemotherapy(HAIC) in treating primary liver cancer with portal vein tumor thrombosis(PVTT). Methods Fifty patients with primary liver cancer complicated with portal vein thrombosis admitted for treatment from August 2021 to August 2022 were randomly separated into an PD-1 group(n=25) and a control group(n=25) using a random number table method. The control group was treated with thymosin α1 and HAIC, while the PD-1 group was treated with PD-1 antibody combined with thymosin α1 and HAIC. The objective response rate, liver function indicators, serum tumor markers, and immune function indicators were compared between the two groups. Results The objective response rate of PD-1 group was higher than that of control group(48.00% vs. 20.00%,χ2/P=4.367/0.037). After 6 and 12 weeks of treatment, both groups showed an increase in albumin(Alb) level, and PD-1 group was higher than that in control group after 12 weeks of treatment. Both groups showed a decrease in total bilirubin(TBil) and alanine aminotransferase(ALT), and PD-1 group was lower than those in control group after 12 weeks of treatment(t/P=2.897/0.006, 3.424/<0.001, 2.658/<0.001). After 6 and 12 weeks of treatment, both groups showed a decrease in alpha fetoprotein(AFP) and insulin-like growth factor binding protein-2(IGFBP-2), and the PD-1 group was lower than those in control group after 12 weeks of treatment(t/P=3.934/<0.001, 5.992/<0.001). After 6 and 12 weeks of treatment, both groups showed a decrease in CD8+, and PD-1 group was lower than the control group after 12 weeks of treatment. CD4+/CD8+ increased in both groups, and PD-1 group was higher than the control group after 12 weeks of treatment(t/P=3.110/<0.001, 2.414/0.020). Conclusion PD-1 antibody combined with thymosin α1 and HAIC therapy can improve liver and immune functions, reduce AFP level, delay tumor progression, and have great therapeutic effects in patients with primary liver cancer complicated with PVTT.
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Predictive value of real-time shear wave elastography elasticity index combined with serum SIL-2R and MMP-2 levels in cervical lymph node metastasis of thyroid micropapillary carcinoma
Author:Chen Hong Qi Kai He Liu Lei Jianwei Li Kang
keyword: Papillary thyroid microcarcinoma; Cervical lymph node metastasis; Real-time shear wave elastography; Soluble interleukin-2 receptor; Matrix metalloproteinase-2;
Objective To investigate the predictive value of real-time shear wave elastography(SWE) elasticity index combined with serum levels of soluble interleukin-2 receptor(sIL-2R) and matrix metalloproteinase-2(MMP-2) in cervical lymph node metastasis of thyroid micropapillary carcinoma(PTMC). Methods Ninety-eight patients with PTMC admitted to the Department of Ultrasound Medicine, Baoji Central Hospital from January 2020 to January 2023 were selected. All patients underwent SWE examination before surgery to detect serum sIL-2R and MMP-2 levels. The patients were divided into a metastatic group(32 cases) and a non-metastatic group(66 cases), and 52 benign thyroid nodule patients were selected as the control group. Multivariate Logistic regression analysis of the factors of cervical lymph node metastasis in PTMC patients. The value of receiver operating characteristic(ROC) curve analysis of SWE parameters and sIL-2R and MMP-2 in predicting cervical lymph node metastasis in PTMC patients. Results The age of metastatic subgroup was lower than that of non-metastatic subgroup, the proportion of multiple lesions, the proportion of envelope invasion, and the tumor diameter were higher than that of non-metastatic subgroup(t/χ2/P=8.867/<0.001, 6.329/0.012, 5.669/0.017, 10.080/<0.001). Emax, Emin and Emean in metastasis subgroups were higher than non-metastasis subgroups and control groups(F/P=100.582/<0.001,289.716/<0.001,183.654/<0.001), but="" there="" was="" no="" significant="" difference="" between="" non-metastasis="" subgroups="" and="" control="" p="">0.05). Serum sIL-2R and MMP-2 levels in metastatic subgroup were higher than those in non-metastasis subgroup and control group(F/P=367.973/<0.001, 414.371/<0.001). Capsular invasion, large tumor diameter, high Emax, high sIL-2R, and high MMP-2 were risk factors for cervical lymph node metastasis in PTMC patients[OR(95%CI)=3.459(1.534-7.802), 2.321(1.144-4.709), 1.902(1.088-3.325), 1.702(1.066-2.719), 1.748(1.078-2.838)]. The area under the curve of Emax, sIL-2R, MMP-2 and the combined prediction of PTMC lymph node metastasis were 0.852, 0.794, 0.795 and 0.931, respectively, and the AUC of the combined prediction was greater than that of the single prediction(Z=1.953, 2.940, 2.674, P=0.023, <0.001, 0.005).Conclusion The Emax value of SWE parameters and the increase of serum sIL-2R and MMP-2 levels in patients with PTMC are associated with cervical lymph node metastasis, and the combination of Emax, sIL-2R and MMP-2 can predict the risk of cervical lymph node metastasis of PTMC.
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Expression of miR-338-3p and PLCD3 in papillary thyroid carcinoma tissues and association with pathological parameters, epithelial-mesenchymal transition and prognosis
Author:Ke Xianfeng Li Qiang Xiang Hui Cui Yi Lei Zhenzhen
keyword: Papillary thyroid carcinoma; Micro ribonucleic acid-338-3p; Phospholipase C delta 3; Pathological parameters; Epithelial-mesenchymal transition; Prognosis;
Objective To investigate the expression of micro ribonucleic acid-338-3p(miR-338-3p) and phospholipase C delta-3(PLCD3) in papillary thyroid carcinoma(PTC) tissues and their relationship with pathological parameters, epithelial-mesenchymal transition(EMT) and prognosis. Methods 152 cases of PTC patients admitted to the Breast and Thyroid Surgery Department of Shangluo Central Hospital who underwent surgical resection from January 2016 to December 2020 were selected, and real-time fluorescence quantitative polymerase chain reaction was used to detect the expression of miR-338-3p and PLCD3 mRNA in cancer tissues and corresponding para-cancerous tissues, and immunohistochemistry was used to detect the expression of EMT-associated proteins [N-calmodulin(N-Cad), E-calmodulin(E-Cad), and vimentin(VIM)]. The relationship between miR-338-3p, PLCD3 mRNA expression and pathological parameters of PTC were analyzed. The binding sites of miR-338-3p and PLCD3 were predicted by Targetscan database, and the correlation between miR-338-3p and PLCD3 mRNA and the expression of both with EMT-related proteins in PTC tissues was analyzed by Pearson's method and dichotomous correlation. PTC tissues were divided into high/low miR-338-3p, PLCD3 mRNA expression groups according to the mean values of miR-338-3p, PLCD3 mRNA expression, and the survival curves of disease-free survival(DFS) of PTC patients with high/low miR-338-3p, PLCD3 mRNA expression were plotted by Kaplan-Meier method. Factors of DFS in PTC patients were analyzed by Cox regression. Results Compared with para-cancerous tissues, miR-338-3p expression and E-Cad protein positive expression rate were decreased in PTC tissues, and PLCD3 mRNA expression and N-Cad and VIM protein positive expression rate were increased(t/χ2/P=32.875/<0.001, 15.575/<0.001, 37.351/<0.001, 21.984/<0.001, 16.604/<0.001). miR-338-3p was negatively correlated with PLCD3 mRNA expression in PTC tissues(r/P=-0.712/<0.001). miR-338-3p was negatively correlated with the positive expression rate of N-Cad and VIM proteins, and positively correlated with that of E-Cad proteins in PTC tissues(r/P=-0.642/<0.001,-0.617/<0.001, 0.622/<0.001); PLCD3 mRNA was negatively correlated with N-Cad in PTC tissues, VIM protein positive expression rate was positively correlated with E-Cad protein positive expression rate(r/P=0.657/<0.001, 0.624/<0.001,-0.632/<0.001). Comparison of miR-338-3p and PLCD3 mRNA expression in PTC tissues with different TNM stages and lymph node metastasis showed differences(F/t/P=30.778/<0.001, 3.430/0.001). 3-year DFS was higher in the miR-338-3p high-expression group than that in the miR-338-3p low-expression group, and 3-year DFS was lower in the PLCD3 mRNA high-expression group than that in the PLCD3 mRNA low-expression group(χ2/P=15.615/<0.001, 16.088/<0.001). TNM stage Ⅲ, lymph node metastasis, and PLCD3 mRNA ≥1.83 were independent risk factors for DFS in PTC patients, and miR-338-3p ≥0.57 was an independent protective factor[HR(95%CI)=3.127(1.361-7.604), 2.546(1.115-5.817), 2.854(1.178-6.919), 0.306(0.116-0.804)]. Conclusion Low expression of miR-338-3p and high expression of PLCD3 mRNA in PTC tissues are associated with TNM staging, lymph node metastasis, EMT and prognosis, and may become a new target for PTC diagnosis and treatment.