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 interaction between immune cell infiltration and extracellular matrix (ECM) in diffuse gastric cancer (DGC), and to identify novel diagnostic biomarkers and therapeutic targets. MethodsTranscriptomic data of DGC patients from The Cancer Genome Atlas (TCGA) database were analyzed to screen potential regulator factor of immune-related and ECM receptor-related signaling pathways. Differential expression of the identified regulator was assessed between the DGC tissues and the adjacent gastric tissues. Bioinformatics analysis was utilized to evaluate the relation between the regulator factor and immune cell infiltration and ECM, as well as prognosis. The clinical validation was performed using 90 paraffin-embedded DGC tissues and adjacent gastric tissues from the patients treated at The Lanzhou University Second Hospital (hereafter “our hospital”) from January 2017 to December 2019. The immunohistochemical staining was employed to examine the expression of regulator factor, followed by analysis of its association with immune cell infiltration, clinicopathologic features, and prognosis. Additionally, 10 paired DGC tissues and adjacent gastric tissues from the patients treated in our hospital in 2024 were collected for validation using real-time quantitative PCR to assess mRNA expression. The significance level was set at α=0.05. ResultsThe collagen type I alpha 1 chain (COL1A1), a potential regulator factor linked to immune and ECM receptor signaling pathways, was identified from the TCGA database. The COL1A1 was significantly overexpressed in the DGC tissues compared to the adjacent gastric tissues (P<0.001), and its high expression correlated with poorer prognosis [HR(95%CI)=2.98(1.21, 7.30), P=0.017]. The COL1A1 gene expression negatively correlated with CD8+ T cell enrichment score (CIBERSORT: r=−0.17, P<0.001; xCELL: r=−0.32, P<0.001) but positively correlated with M2 tumor-associated macrophage enrichment score (CIBERSORT: r=0.32, P<0.001; xCELL: r=0.24, P<0.001). The clinical validation confirmed that the COL1A1 protein and mRNA were both overexpressed in the DGC tissues (P<0.001). The patients with high COL1A1 protein expression had worse overall survival (P<0.001), and high expression (vs. low) was an independent risk factor for postoperative overall survival [HR(95%CI)=6.607(3.374, 12.940), P<0.001]. The COL1A1 protein expression positively correlated with CD163 (an M2 macrophage marker; r=0.76, P<0.001) and negatively with CD8+ (T cell marker, r=−0.84, P<0.001). ConclusionThis study demonstrates that COL1A1 is a potential therapeutic target for immune suppression and ECM interaction in DGC and a critical prognostic factor for long-term survival in patients with DGC.
ObjectiveTo understand the mechanisms of malnutrition in patients with gastric cancer (GC) and which affecting on therapy outcomes, and explore effective nutritional intervention strategies so as to improve general therapy outcomes for patients with GC. MethodThe literature on studies relevant malnutrition in the patients with GC both domestically and internationally was reviewed and analyzed. ResultsThe mechanisms of malnutrition in the patients with GC are complex and diverse, including abnormal tumor metabolism, side effects of treatment, psychological and economic factors, etc. The malnutrition made the mortality and recurrence rates increase, hospital stay prolong, and medical costs elevate, meanwhile led to the multiple complications. The use of various screening tools could effectively assess the malnutrition status at the different therapy stages, then the individualized nutritional therapy plans could be developed based on the assessment results. These plans included oral nutrition, enteral nutrition, parenteral nutrition, and immunonutrition. ConclusionsMalnutrition severely affects the treatment outcomes and quality of life of patients with GC. It is necessary to timely screen and assess. The reasonable nutritional support plan should be chosen based on the patient’s individualized situation. Future research should be needed to explore the long-term efficacy and safety of nutritional support, optimize the application of immunonutrition and parenteral nutrition, and enhance the general treatment outcomes for patients with GC.
ObjectiveTo investigate the value of metastatic lymph node ratio (abbreviation: rN) in the prognosis of patients with gastric cancer.MethodsThe clinical data of 255 patients with gastric cancer who underwent the radical gastrec-tomy in the First Department of General Surgery of Lanzhou University Second Hospital from January 2014 to July 2019 were retrospectively reviewed. The survival analysis was performed using Kaplan-Meier survival curves and Cox regression model. The receiver operating characteristic (ROC) curve was used to compare the accuracy of rN stage and N stage for prognosis judgment of patients with gastric cancer, and the Spearman correlation analysis method was used to analyze the correlation between rN or number of metastatic lymph node and total number of lymph nodes detected.ResultsThe univariate survival analysis showed that the vascular invasion, nerve invasion, histologic grade, tumor diameter, T stage, N stage, and rN stage were significantly associated with the prognosis of patients with gastric cancer (P<0.05); The multivariate survival analysis demonstrated that the prognosis model based on the rN stage had a higher HR value (1.756 versus 1.610) and a smaller –2 log likelihood value (648.548 versus 649.469) than the N stage. Correlation analysis results showed that rN was indepen-dent of the number of lymph nodes detected when the number was <15 and ≥15 (rs=0.275, P=0.058; rs=0.075, P=0.285). In addition, when the number of lymph nodes detected was <15 and ≥15, the rN staging could accurately stratify the prognosis of gastric cancer patients (χ2=11.24, P=0.009; χ2=30.25, P<0.001). ROC curve analysis results showed that when the number of lymph nodes detected was less than 15, rN stage had a higher area under ROC curve value [0.863, 95%CI (0.752, 0.974) and 0.813, 95%CI (0.687, 0.938)] as compared with N stage.ConclusionrN stage might be more accurate than N stage in predicting prognosis of patients with gastric cancer when number of lymph nodes harvested is less than 15.
目的 比较开腹、腹腔镜和经皮肝穿刺引流3种方法治疗细菌性肝脓肿的优劣性,为细菌性肝脓肿治疗方法的选择提供参考依据。方法 回顾性分析笔者所在医院2010年9月至2011年7月期间收治的39例细菌性肝脓肿患者的临床资料,根据其治疗方式将患者分为开腹组、腹腔镜组和经皮经肝穿刺引流组(穿刺组)3组,对3组的首次治愈者比例、1个月治愈者比例、发生并发症者比例、住院时间及住院费用进行比较。结果 开腹组、腹腔镜组和穿刺组首次治愈者比例分别为10/12、8/9及12/18,3组间差异有统计学意义(P<0.05); 1个月治愈者比例分别为11/12、9/9及17/18,3组间差异无统计学意义(P>0.05);发生并发症者比例分别为2/12、1/9及2/18,腹腔镜组和穿刺组之间的差异无统计学意义(P>0.05),2组与开腹组相比差异均有统计学意义(P<0.05);住院时间分别为(15.4±4.5) d、(9.7±2.3) d及 (16.7±5.8) d (P<0.05);住院费用分别为(1.9±0.5)万元、(1.3±0.3)万元及(0.8±0.2)万元(P<0.05)。结论 开腹组、腹腔镜组和穿刺组3种治疗方法各有利弊,个体化选择治疗方式是肝脓肿的治疗策略。
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 construct the eukaryotic expressive vector of human tissue factor (TF),and to abserve the effect of TF on invasion and metastasis of gastric cancer cells line. Methods The human TF cDNA was obtained from human placenta by nest PCR, and the constructed eukaryotic expressive vector TF-pcDNA3 was transfected into SGC7901 cells by lipofectamine. Stable-transfected cells were screened by G418. The expressions of TF mRNA and protein on the cells were detected by RT-PCR and Western blot. Cell motility was assessed by using Transwell experiments and wound-healing assays. Results The eukaryotic expressive vector TF-pcDNA3 was successfully constructed and transfected into SGC7901. Compared with blank control group and negative control group, the expressions of TF mRNA and TF protein in transfection group were increased, the cell motility in vitro was enhanced. Conclusion TF can enhance the ability of invasion and metastasis of gastric cancer cells in vitro.
Objective To analyze and summarize the research progression of phenotypic markers of hepatic sinusoidal endothelial cell (HSEC) and its role in the development and progression of the liver diseases. Methods Databases such as PubMed, Wanfang, CNKI, etc were retrieved for the latest articles on research advance in HSEC using “hepatic sinus endothelial cell”, “liver regeneration”, and “liver disease” as key words. All of the publications about studies on relation between HSEC and liver disease were reviewed and summarized. Results HSEC with specific cytoarchitectures and phenotypic markers was initially received “the message of damage” in the process of liver regeneration, hepatic immunological tolerance, hepatic fibrosis, and liver damage. Additionally, HSEC as the first barrier not only enabled liver to be protected but also was regarded as the first alternation of liver damage. Therefore, HSEC played a great important role in the process of the onset and progression of the liver disease. Conclusions The function of HSEC is complex. How do play a role and its the mechanism is unclarified, it is needed to be further studied.