ObjectiveTo investigate the expression of Runt-related transcription factor 1 (RUNX1) in gastric cancer and its correlation with clinicopathological features, prognosis and tumor cell invasion ability. Methods① Database analysis: the expression of RUNX1 in gastric cancer and adjacent tissues were analyzed by TCGA and GEO database. Kaplan-Meier Plotter database was used to analyze the correlation between RUNX1 expression level and overall survival (OS) of gastric cancer patients. GO analysis and KEGG pathway enrichment were used to analyze the possible functions and signaling pathways of RUNX1 in gastric cancer, and gene correlation was verified by GEPIA database. ② Clinical case validation: the cancer tissues and adjacent tissues of 62 patients with gastric cancer admitted to the Second Hospital of Lanzhou University from June 2018 to December 2019 were retrospectively collected for immunohistochemical staining, HE staining and Sirius red staining, and the relation between RUNX1 expression and clinicopathological features and prognosis of patients was explored. ③ Cell experiment: we knocked down RUNX1 by using small interfering RNA, and then analyzed the relation between RUNX1 and the invasion ability of gastric cancer cells by Transwell assay. Results① Database analysis: RUNX1 was highly expressed in gastric cancer tissues and negatively correlated with OS (P<0.001). GO analysis and KEGG pathway enrichment analysis showed that RUNX1 was not only involved in the construction of collagen in extracellular matrix (ECM), but also significantly enriched in ECM-receptor interaction pathway. The results of GEPIA gene correlation analysis showed that RUNX1 was positively correlated with gene expression involved in ECM-receptor interaction pathway (P<0.05). ② Clinical case validation: the results of immunohistochemical staining showed that RUNX1 was relatively highly expressed in gastric cancer tissues, and the high expression of RUNX1 was a risk factor affecting the postoperative OS of gastric cancer patients (RR=5.074, P=0.034); the expression of RUNX1 in gastric cancer tissues was positively correlated with red staining area of Sirius red staining (r=0.46, P<0.001). ③ Cell experiment: invasion experiments confirmed that the number of invasive AGS or HGC27 cells in si-001 group and si-002 group decreased after RUNX1 knockdown. ConclusionRUNX1 is highly expressed in gastric cancer and suggests a worse survival prognosis, and it is possible that RUNX1 promotes the development of gastric cancer by activating the ECM-receptor interaction pathway.
ObjectiveTo explore the factors of affecting the prognosis of pancreatic ductal adenocarcinoma (PDAC) after radical resection based on the preoperative systemic immune-inflammation index (SII) and the controlling nutritional status (CONUT) score and to establish a prognostic prediction model.MethodsThe clinicopathologic data of patients diagnosed with PDAC from January 2014 to December 2019 in the Second Hospital of Lanzhou University were retrospectively analyzed. The X-tile software was used to determine the optimal cut-off value of SII. The Kaplan-Meier method was used to analyze survival. The Cox proportional hazards regression model was used to conduct multivariate analysis of prognostic factors of PDAC after radical surgery. R4.0.5 software was used to draw a nomogram prediction model of 1-, 2-, and 3-year survival rates, then evaluate the effectiveness of the prediction model and establish a web page calculator.ResultsA total of 131 patients were included in the study. The median survival time was 18.6 months, and the cumulative survival rates at 1-, 2-, and 3-year were 73.86%, 36.44%, and 11.95%, respectively. The optimal cut-off value of preoperative SII was 313.1, and the prognosis of patients with SII>313.1 was worse than SII≤313.1 (χ2=8.917, P=0.003). The results of multivariate analysis suggested that the age>65 years old, clinical stage Ⅲ and Ⅳ, preoperative SII>313.1, and CONUT score >4 were the independent factors influencing the prognosis (overall survival) for PDAC after radical resection (P<0.05). The internal verification consistency index (C-index) of the nomogram prediction model including age, clinical stage, preoperative SII, CONUT score and postoperative chemotherapy was 0.669. The survival predicted by the nomogram correction curve fitted well with the observed survival. The decision curve analysis showed that the nomogram prediction model had a wider clinical net benefit (Threshold probability was 0.05–0.95), and the web calculator worked well.ConclusionsAge, clinical stage, preoperative SII, CONUT score are independent influencing factors for prognosis after radical PDAC surgery. Nomogram prediction model included these independent influencing factors is more accurate and web calculator will be more convenient for doctors and patients.
Objective To understand the development, research status, advantages and disadvantages of patient-derived organoid (PDO) and patient-derived tumor xenograft (PDX), and to summarize their applications in pancreatic cancer, so as to provide new ideas for the selection of early modeling of pancreatic cancer. Method The recent studies on PDO and PDX of pancreatic cancer at home and abroad were reviewed. Results The PDO and PDX models had a wide range of applications in preclinical research of tumor, especially played an important role in the basic research of present pancreatic cancer patients with poor clinical treatment effects, such as the pathogenesis research of pancreatic cancer, developing new targets and new drugs, testing preclinical drug toxicity and effectiveness. Conclusion PDO and PDX, as classical tumor research model, have broad clinical application prospects in the research of pancreatic cancer.
Objective To systematically evaluate the safety and efficacy of trastuzumab combined with chemotherapy for HER-2 positive patients with advanced gastric cancer. Methods We searched ClinicalTrails.gov, PubMed, EMbase, Web of Science, The Cochrane Library (Issue 5, 2016), CNKI, CBM, WanFang Data, VIP and major meeting proceeding databases (ASCO and ESMO) from inception to May 2016, to collect randomized controlled trials (RCTs) or non-RCTs about trastuzumab combined with chemotherapy versus chemotherapy alone for advanced gastric cancer. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was performed by using RevMan 5.3 software. Results Nine studies involving 1 034 HER-2 positive patients were included, of which three were RCTs and the other six were non-RCTs. Meta-analysis results indicated that the trastuzumab combined with chemotherapy group (the trial group) was superior to the chemotherapy alone group (the control group) in complete remission (OR=2.76, 95%CI 1.40 to 5.44,P=0.003), partial remission (OR=1.81, 95%CI 1.40 to 2.33,P<0.000 01), overall response rate (OR=2.09, 95%CI 1.63 to 2.68,P<0.000 01) and disease control rate (OR=2.20, 95%CI 1.63 to 2.98,P<0.000 1), while there was no statistical significances in stable disease (OR=0.87, 95%CI 0.66 to 1.14,P=0.31). In terms of safety, the incidence of diarrhea (OR=1.51, 95%CI 1.10 to 2.06,P=0.01) and erythra (OR=4.35, 95%CI 1.25 to 15.10,P=0.02) in the trial group were higher than the control group. However, other adverse reactions were no significant differences in two groups. Conclusion Compared with chemotherapy alone, trastuzumab combined with chemotherapy in the treatment of HER-2 positive patients with advanced gastric cancer can significantly improve response rate, but it may increase the incidence of diarrhea and erythra. Because of the limited quality and quantity of the included studies, the above conclusion needs to be verified by conducting more high quality studies.
ObjectiveTo systematically review the efficacy and safety of neoadjuvant chemotherapy containing tegafur gimeracil oteracil potassium (S-1) combined with surgery in the treatment of advanced gastric cancer.MethodsWe searched EMbase, PubMed, The Cochrane Library, Web of Science, CBM, CNKI and WanFang Data from inception to February 2017, to collect randomized controlled trials (RCTs) about neoadjuvant chemotherapy containing S-1 combined with surgery in the treatment of advanced gastric cancer. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Meta-analysis was performed by using RevMan 5.3 software.ResultsA total of 11 RCTs involving 971 advanced gastric cancer patients were included. The results of meta-analysis showed that the neoadjuvant chemotherapy containing S-1 combined with surgery group was superior to the control group in R0 resection rate (OR=2.75, 95%CI 1.91 to 3.95, P<0.000 01), 2 year survival rate (OR=1.72, 95%CI 1.01 to 2.93, P=0.05) and 3 year survival rate (OR=1.64, 95%CI 1.12 to 2.41, P=0.01), while there were no statistical differences in response rate (OR=1.33, 95%CI 0.70 to 2.51, P=0.39), 1 year survival rate (OR=1.50, 95%CI 0.64 to 3.53, P=0.35) and the incidence of postoperative complications (OR=1.00, 95%CI 0.66 to 1.51, P=0.98).ConclusionNeoadjuvant chemotherapy containing S-1 combined with surgery can improve the R0 resection rate, 2-year survival rate and 3-year survival rate without increase postoperative complications rate. Due to limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusion.
Objectives To systematically review the efficacy and safety of docetaxel or epirubicin based regimens in the treatment of advanced gastric cancer. Methods We searched EMbase, PubMed, The Cochrane Library, Web of Science, CBM, CNKI and WanFang Data from inception to March 2017, to collect randomized controlled trials (RCTs) on docetaxel or epirubicin based regimens in the treatment of advanced gastric cancer. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Meta-analysis was performed by using RevMan 5.3 software. Results A total of 12 RCTs involving 984 advanced gastric cancer patients were included. The results of meta-analysis showed that docetaxel based regimens were superior to epirubicin based regimens in ORR (RR=1.21, 95%CI 1.02 to 1.43, P=0.03), DCR (RR=1.13, 95%CI 1.01 to 1.26, P=0.03), 1-year survival rate (RR=1.26, 95%CI 1.01 to 1.56, P=0.04) and 2-year survival rate (RR=3.03, 95%CI 1.59 to 5.75, P=0.000 7), while there was no statistical difference between two groups in the incidence of grade Ⅲ to Ⅳ adverse events. The results of sensitivity analysis showed that docetaxel based regimens were superior to epirubicin based regimens in 2-year survival rate (RR=2.56, 95%CI 1.06 to 6.19, P=0.04), but there were no statistical differences in ORR (RR=1.13, 95%CI 0.88 to 1.45, P=0.34), DCR (RR=1.02, 95%CI 0.85 to 1.21, P=0.84) and 1-year survival rate (RR=1.29, 95%CI 0.92 to 1.80, P=0.14). The results of sensitivity analysis indicated that the overall outcomes might be affected by the risk bias of included studies. The comparision between docetaxel based regimens and epirubicin based regimens was consistent with the overall outcomes in the incidence of grade Ⅲ to Ⅳ adverse events. Conclusions Compared with epirubicin based regimens, docetaxel based regimens may have more clinical benefits for advanced gastric cancer patients. Due to limited quality and quantity of the included studies, more high quality studies are required to verify above conclusions.
ObjectiveTo investigate differentially expressed genes (DEGs) and potential molecular mechanisms between hepatitis C-related hepatocellular carcinoma (HCV-HCC) and hepatitis B-related HCC (HBV-HCC). MethodsThe data of HCV-HCC and HBV-HCC gene expressions were downloaded and integrated from the public gene expression database, and the limma package was used to investigate the DEGs between the HCV-HCC and HBV-HCC samples. The gene set enrichment analysis (GSEA) was used to explore the differences in suppressed or activated gene sets between the HCV-HCC and HBV-HCC samples, and the MCODE was used to explore the key molecular modules, and then the potential biological processes and molecular pathways of the key molecular modules were analyzed. The effect of key genes on survival of the HCC patients was analyzed by the Kaplan-Meier-Plotter database.ResultsIn this study, 119 HBV-HCC samples and 163 HCV-HCC samples were obtained, and the 199 DEGs were screened out. Compared with HBV-HCC, the activated gene sets of HCV-HCC were mainly enriched in the gene sets of inflammation, complement, up-regulation of genes in response to interferon, up-regulation of genes in response to KRAS, genes regulated by the nuclear factor- κB-tumor necrosis factor pathway, and apoptosis. However, the cell cycle-related gene sets were obviously suppressed. Eight key molecular modules enriched by DEGs were found, which included 18 key genes (IFI27, DDX60, MX1, IRF9, OAS3, OAS1, RSAD2, GBP4, HERC6, ISG15, IFIT1, CMPK2, EPSTI1, IFI44, IFI44L, HERC5, IFITM1, CXCL10). GO analysis showed that the biological process was mainly concentrated in the body response related to virus infection, the molecular component was mainly in the host cells, and the molecular function was mainly enriched in the biological combination. KEGG analysis showed that the key genes were mainly involved in the molecular signaling pathway related to virus infection. The survival analysis showed that the 9 key genes (CXCL10, HERC6, DDX60, IFITM1, IFI27, GBP4, IFI44L, IFI44, MX1) were closely related to better prognosis of patients with HCC (HR<1, P<0.05). ConclusionsThere is an essential difference between HBV-HCC and HCV-HCC. Occurrence of HCV-HCC is mainly related to virus infection and immune response induced by the virus. Therefore, for HCV infection, active antiviral treatment is necessary for avoiding hepatitis turning into chronic viral infection and preventing or blocking HCV infection converting to HCC.
ObjectiveTo evaluate prognostic value of change of immune status in locally advanced gastric cancer (LAGC) patients. Methods We retrospective collected 210 LAGC patients who underwent treatment in our department from January 2013 to December 2018, then we collected lymphocyte-to-monocyte ratio (LMR) and cLMR (change of lymphocyte-to-monocyte ratio, cLMR) before operation and after three cycles of adjuvant chemotherapy. We had developed a new immune state change score (ICS) based on preoperative LMR (pLMR) and cLMR, and explored its prognostic value. The definition of ICS in this study was: ICS=1, pLMR≤4.53 and cLMR≤1; ICS=2, pLMR≤4.53 and cLMR>1, or pLMR>4.53 and cLMR≤1; ICS=3, pLMR>4.53 and cLMR>1. Results The results of multivariate Cox proportional hazard regression model showed that ICS was an influencing factor for overall survival [ICS=2, RR=0.397, 95%CI (0.260, 0.608), P<0.001; ICS=3, RR=0.080, 95%CI (0.040, 0.162), P<0.001), patients with ICS scores of 2 and 3 had better overall survival. In addition, the prognostic accuracy of ICS was superior to pLMR and Clmr, and the C-index of ICS [0.806, 95%CI (0.746, 0.865)] was higher than that of pLMR [0.717, 95%CI (0.635, 0.799), P=0.003)] and cLMR [0.723, 95%CI (0.641, 0.806), P=0.005)]. Based on this, a Nomogram model included ICS, CEA, and pTNM staging was constructed to predict the 3-year and 5-year survival rates of patients. The calibration curve and C-index [0.821, 95%CI (0.783, 0.859)] showed high discrimination and accuracy of Nomogram, and decision curve analysis confirmed that the model had good clinical application value. Conclusions The dynamic changes in the patient’s immune status before and after adjuvant therapy are related to the overall survival of LAGC patients. As an evaluating system which combined the cLMR and pLMR, ICS can better predict the prognosis of LAGC patients.