ABSTRACT
Objective:To screen the endoplasmic reticulum stress (ERS) signature-related differentially expressed genes (DEG) in gastric cancer and to construct a prognostic risk model based on a bioinformatics.Methods:Transcriptome sequencing data (RNA-seq) of 375 gastric cancer and 32 paracancerous tissue samples downloaded from The Cancer Genome Atlas (TCGA) database and the corresponding clinical information were obtained as training set samples; data of 387 gastric cancer patients (GSE84437) from Gene Expression Omnibus (GEO) database were downloaded as validation set samples. All data were obtained on December 25, 2021. A total of 785 ERS signature-related genes (ERS-RG) were obtained from the GeneCards database. DEG between gastric cancer tissues and paracancerous tissues in the TCGA database was analyzed. The identified gastric cancer DEG were intersected with ERS-RG from the GeneCards database to obtain gastric cancer ERS signature-related DEG, which were analyzed for gene ontology (GO) function and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Univariate Cox proportional risk model was used to screen ERS signature-related DEG with prognostic value in gastric cancer, and LASSO regression analysis was performed to construct a polygenic prognostic risk model, and to calculate the prognostic risk score. The patients in training set and validation set were divided into high-risk group and low-risk group according to the median of the prognostic risk score (2.369); Kaplan-Meier survival analysis was used to compare the overall survival (OS) and to draw time-dependent receiver operating characteristic (ROC) curves of patients in the two groups; nomogram was drawn based on the prognostic independent influencing factors of gastric cancer. The characteristic immune cell infiltration abundance between the two groups was analyzed by using the inverse convolution-based CIBERSORT algorithm. Cytolytic activity scores were calculated by using the geometric mean of granzyme A and perforin 1 expression. According to the median prognostic risk score (2.369) and median tumor mutation burden (TMB) (3.000), all patients with gastric cancer were divided into high risk score-high TMB group, high risk score-low TMB group, low risk score-high TMB group and low risk score-low TMB group to compare the OS of patients in each group.Results:A total of 444 ERS signature-related DEG in gastric cancer including 168 down-regulated genes and 276 up-regulated genes were obtained, which were mainly enriched in biological processes such as protein processing in the endoplasmic reticulum, extracellular matrix (ECM) receptor interactions and unfolded protein responses (all P < 0.05). Univariate Cox regression analysis showed that 12 prognostic-related ERS signature-related DEG in gastric cancer were screened out. LASSO regression analysis was performed to obtain a prognostic risk score = 0.052×NOS3+0.137×PON1+0.067×CXCR4+0.131×MATN3+0.116×ANXA5+0.090×SERPINE1. The results of Kaplan-Meier analysis showed that the OS of the low-risk group in both the training and validation sets was better than that of the high-risk group (all P < 0.01). The results of the time-dependent ROC curve analysis showed that the AUC for the 3-year, 5-year, 8-year OS rates was 0.695, 0.786, 0.698, respectively in the training set, while the AUC for the 3-year 5-year, 8-year OS rates was 0.580, 0.625, 0.627, respectively in the validation set. Multivariate Cox regression analysis showed that prognostic risk score ( HR = 3.598, 95% CI 2.290-5.655, P < 0.001) and tumor stage ( HR = 1.344, 95% CI 1.057-1.709, P < 0.05) were independent factors influencing the prognosis of gastric cancer. Among 375 gastric cancer patients in the TCGA database, the expression levels of ATF6, HSPA5, XBP1 and ATF4 in the high-risk group were higher than those in the low-risk group (all P < 0.05); CIBERSORT results showed that the abundance of activated CD4 memory T cells in the high-risk group was lower than that in the low-risk group, and the abundance of both M0 and M2 macrophages in the high-risk group was higher than that in the low-risk group (all P < 0.05). The expression levels of common immune checkpoints (CD274, CTLA4, TNFRSF9, TIGIT, PDCD1, LAG3) in the high-risk group were all higher than those in the low-risk group (all P < 0.05). Cytolytic activity score in the high-risk group was higher than that in the low-risk group ( P < 0.05). The prognostic risk score was negatively correlated with TMB ( r = -0.20, P < 0.001). Patients in the low-risk score-high TMB group had the best OS and those in the high-risk score-low TMB group had the worst OS (both P < 0.001). Conclusions:The prognostic risk score model is established based on 6 ERS signature-related DEG in gastric cancer and its prognostic risk score may be effective as an independent prognostic factor to predict the prognosis of gastric cancer patients.
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Objective:To investigate the efficacy and safety of argon plasma coagulation (APC) in the treatment of patients with hemorrhagic chronic radiation proctitis (HCRP).Methods:The clinical data of 36 HCRP patients who received APC treatment in Shanxi Province Cancer Hospital between January 2017 and June 2021 were retrospectively analyzed. The severity of HCRP was assessed by using the Zinicola endoscopic score and the Vienna proctoscopy score. The elimination of rectal bleeding or occasional bloody stools that did not require further treatment within 6 months of the last APC treatment was considered to be the therapy success.Results:The median follow-up time was 1.63 years (0.85-2.68 years). There were 20 (55.6%) patients with severe HCRP according to the Zinicola endoscopic score. After APC treatment, 32 patients with HCRP obtained adequate rectal hemostasis, whereas 4 patients with severe HCRP still experienced rectal bleeding symptoms after APC treatment for several times. All patients received APC treatment for (2.7±1.0) times in total. The endoscopic scores of HCRP patients before and after APC treatment were (3.6±0.8) scores, (1.4± 1.1) scores, respectively; Vienna proctoscopy scores were (3.8±0.8) scores, (1.2±1.1) scores, respectively; and the differences were statistically significant ( t values were 22.37, 18.96; all P < 0.001). The hemoglobin levels of HCRP patients before and after APC treatment were (85±15) g/L, (100±17) g/L, respectively, and the difference was statistically significant ( t = 17.86, P < 0.001). Serious side effects including strictures, perforations, or fistulas and other severe complications related to APC therapy were not found. Conclusions:APC may be an effective and safe treatment option for patients with HCRP.
ABSTRACT
In recent years, the eradication rate of standard triple therapy for Helicobacter pylori (Hp) infection has been reduced to less than 80% because of many factors, such as strain variation, drug resistance and cross infection of different strains.As more and more cases with failure of initial eradication therapy, the focus of clinical practice is to explore new alternative rescue therapies.Aims: To assess the efficacy and safety of Saccharomyces boulardii combined with moxifloxacin-based triple regimen for rescue therapy of Hp infection.Methods: A total of 400 patients with chronic gastritis who had failed initial bismuth quadruple therapy were enrolled and randomly assigned into two groups: 200 cases of control group and 200 cases of test group.Patients in control group received a rescue triple therapy (esomeprazole, amoxicillin and moxifloxacin) for 14 days and those in test group with the further addition of Saccharomyces boulardii sachets.Hp eradication was assessed by 13C/14C-urea breath test four weeks after treatment, and the adverse events during treatment course were observed.Results: The Hp eradication rates in control group and test group were 80.1% (121/151) and 90.4% (142/157) by per-protocol (PP) analysis, respectively, and 60.5% (121/200) and 71.0% (142/200) by intention-to-treat (ITT) analysis, respectively.The eradication rate in test group was significantly higher than that in control group by both PP and ITT analyses (P<0.05).The incidence rate of adverse events was significantly lower in test group than in control group (9.6% vs.17.9%, P<0.05).Conclusions: Saccharomyces boulardii added to moxifloxacin-based rescue triple therapy could increase the eradication rate of Hp infection with less adverse events.