A pan-cancer analysis of the biological function and clinical value of BTLA in tumors

B and T-lymphocyte attenuator(BTLA)plays an immunosuppressive role by inhibiting T-and B-cell functions.BTLA is associated with a variety of diseases,especially cancer immunity.However,the function of BTLA in various cancers and its clinical prognostic value have still not been comprehensively analyzed.This study aimed to identify the relationship between BTLA and cancer from the perspectives of differences in BTLA expression,its clinical value,immune infiltration,and the correlation with immune-related genes in various cancers.Data regarding mRNA expression,miRNA expression,lncRNA expression,and clinical data of patients of 33 existing cancers were collected from the TCGA database.Target miRNA of BTLA and the lncRNA that interacts with the target miRNA were obtained from the StarBase database.Based on bioinformatics analysis methods,the relationship between various types of cancers and BTLA was thoroughly investigated,and a competing endogenous RNA network of BTLA,target miRNA,and interacting lncRNA was constructed.The Kaplan-Meier(KM)prognostic analysis of BTLA and target miRNA(has-miR-137)in various types of cancers was completed using the KM plotter.BTLA expression varied in different cancers,with statistical significance in nine cancer types.KM plotter to analyze the overall survival(OS)and regression-free survival prognosis of cancer patients revealed that the BTLA expression was statistically different in the OS of 11 types of cancers out of 21 types of cancers;the OS of 8 type of cancers was also statistically different.Correlation analysis of tumor immune genes revealed a positive correlation of BTLA expression with immunosuppressive gene(CTLA4 and PDCD1)expression.Gene Set Enrichment Analysis showed that BTLA and its co-expressed genes mainly act through biological processes and pathways,including immune response regulation,cell surface receptor signaling pathway,antigen binding,antigen receptor-mediated signaling pathway,and leukocyte migration.BTLA has the potential as a prognostic marker for CLL,COAD,NSCLC,and OV and a diagnostic marker for CLL,COAD,and KIRC.BTLA has a close and complex relationship with the occurrence and development of tumors,and cancer immunotherapy for BTLA is worthy of further analysis.

Analysis of the potential biological value of pyruvate dehydrogenase E1 subunitβin human cancer

BACKGROUND The pyruvate dehydrogenase E1 subunitβ(PDHB)gene which regulates energy metabolism is located in mitochondria.However,few studies have elucidated the role and mechanism of PDHB in different cancers.AIM To comprehensive pan-cancer analysis of PDHB was performed based on bioinformatics approaches to explore its tumor diagnostic and prognostic value and tumor immune relevance in cancer.In vitro experiments were performed to examine the biological regulation of PDHB in liver cancer.METHODS Pan-cancer data related to PDHB were obtained from the Cancer Genome Atlas(TCGA)database.Analysis of the gene expression profiles of PDHB was based on TCGA and Genotype Tissue Expression Dataset databases.Cox regression analysis and Kaplan-Meier methods were used to assess the correlation between PDHB expression and survival prognosis in cancer patients.The correlation between PDHB and receiver operating characteristic diagnostic curve,clinicopathological staging,somatic mutation,tumor mutation burden(TMB),microsatellite instability(MSI),DNA methylation,and drug susceptibility in pan-cancer was also analyzed.Various algorithms were used to analyze the correlation between PDHB and immune cell infiltration and tumor chemotaxis environment,as well as the co-expression analysis of PDHB and immune checkpoint(ICP)genes.The expression and functional phenotype of PDHB in single tumor cells were studied by single-cell sequencing,and the functional enrichment analysis of PDHB-related genes was performed.The study also validated the level of mRNA or protein expression of PDHB in several cancers.Finally,in vitro experiments verified the regulatory effect of PDHB on the proliferation,migration,and invasion of liver cancer.RESULTS PDHB was significantly and differently expressed in most cancers.PDHB was significantly associated with prognosis in patients with a wide range of cancers,including kidney renal clear cell carcinoma,kidney renal papillary cell carcinoma,breast invasive carcinoma,and brain lower grade glioma.In some cancers,PDHB expression was clearly associated with gene mutations,clinicopathological stages,and expression of TMB,MSI,and ICP genes.The expression of PDHB was closely related to the infiltration of multiple immune cells in the immune microenvironment and the regulation of tumor chemotaxis environment.In addition,single-cell sequencing results showed that PDHB correlated with different biological phenotypes of multiple cancer single cells.This study further demonstrated that down-regulation of PDHB expression inhibited the proliferation,migration,and invasion functions of hepatoma cells.CONCLUSION As a member of pan-cancer,PDHB may be a novel cancer marker with potential value in diagnosing cancer,predicting prognosis,and in targeted therapy.

Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer

BACKGROUND A growing number of clinical examples suggest that coronavirus disease 2019(COVID-19)appears to have an impact on the treatment of patients with liver cancer compared to the normal population,and the prevalence of COVID-19 is significantly higher in patients with liver cancer.However,this mechanism of action has not been clarified.Gene sets for COVID-19(GSE180226)and liver cancer(GSE87630)were obtained from the Gene Expression Omnibus database.After identifying the common differentially expressed genes(DEGs)of COVID-19 and liver cancer,functional enrichment analysis,protein-protein interaction network construction and scree-ning and analysis of hub genes were performed.Subsequently,the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was constructed.RESULTS Of 518 common DEGs were obtained by screening for functional analysis.Fifteen hub genes including aurora kinase B,cyclin B2,cell division cycle 20,cell division cycle associated 8,nucleolar and spindle associated protein 1,etc.,were further identified from DEGs using the“cytoHubba”plugin.Functional enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation,cell cycle and other functions,and they may serve as potential molecular markers for COVID-19 and liver cancer.Finally,we selected 10 of the hub genes for in vitro expression validation in liver cancer cells.CONCLUSION Our study reveals a common pathogenesis of liver cancer and COVID-19.These common pathways and key genes may provide new ideas for further mechanistic studies.

Combining systemic inflammatory response index and albumin fibrinogen ratio to predict early serious complications and prognosis after resectable gastric cancer

BACKGROUND Gastric cancer has a high incidence and fatality rate,and surgery is the preferred course of treatment.Nonetheless,patient survival rates are still low,and the incidence of major postoperative complications cannot be disregarded.The systemic inflammatory response,nutritional level,and coagulation status are key factors affecting the postoperative recovery and prognosis of gastric cancer patients.The systemic inflammatory response index(SIRI)and the albumin fibrinogen ratio(AFR)are two valuable comprehensive indicators of the severity and prognosis of systemic inflammation in various medical conditions.AIM To assess the clinical importance and prognostic significance of the SIRI scores and the AFR on early postoperative outcomes in patients undergoing radical gastric cancer surgery.METHODS We conducted a retrospective analysis of the clinicopathological characteristics and relevant laboratory indices of 568 gastric cancer patients from January 2018 to December 2019.We calculated and compared two indicators of inflammation and then examined the diagnostic ability of combined SIRI and AFR values for serious early postoperative complications.We scored the patients and categorized them into three groups based on their SIRI and AFR levels.COX analysis was used to compare the three groups of patients the prognostic value of various preoperative SIRI-AFR scores for 5-year overall survival(OS)and disease-free survival(DFS).RESULTS SIRI-AFR scores were an independent risk factor for prognosis[OS:P=0.004;hazards ratio(HR)=3.134;DFS:P<0.001;HR=3.543]and had the highest diagnostic power(area under the curve:0.779;95%confidence interval:0.737-0.820)for early serious complications in patients with gastric cancer.The tumor-node-metastasis stage(P=0.001),perioperative transfusion(P=0.044),positive carcinoembryonic antigen(P=0.014)findings,and major postoperative complications(P=0.011)were factors associated with prognosis.CONCLUSION Preoperative SIRI and AFR values were significantly associated with early postoperative survival and the occurrence of severe complications in gastric cancer patients.

Systemic inflammatory response index is a predictor of prognosis in gastric cancer patients: Retrospective cohort and meta-analysis

BACKGROUND The systemic inflammatory response index(SIRI)has been demonstrated to make a significant difference in assessing the prognosis of patients with different solid neoplasms.However,research is needed to ascertain the accuracy and reliability of applying the SIRI to patients who undergo robotic radical gastric cancer sur-gery.AIM To validate the applicability of the SIRI in assessing the survival of gastric cancer patients and evaluate the clinical contribution of preoperative SIRI levels to predicting long-term tumor outcomes in patients,who received robotic radical gastric cancer surgery.METHODS Initially,an exhaustive retrieval was performed in the PubMed,the Cochrane Library,EMBASE,Web of Science,and Scopus databases to identify relevant studies.Subsequently,a meta-analysis was executed on 6 cohort studies iden-tifying the value of the SIRI in assessing the survival of gastric cancer patients.Additionally,the clinical data of 161 patients undergoing robotic radical gastric cancer surgery were retrospectively analyzed to evaluate their clinicopathological characteristics and relevant laboratory indicators.The association between preoperative SIRI levels and 5-year overall survival(OS)and disease-free survival(DFS)was assessed.RESULTS The findings demonstrated an extensive connection between SIRI values and the outcome of patients with gastric cancer.Preoperative SIRI levels were identified as an independent hazard feature for both OS and DFS among those who received robotic surgery for gastric cancer.SIRI levels in gastric cancer patients were observed to be associated with the presence of comorbidities,T-stage,carcinoembryonic antigen levels,the development of early serious postoperative complications,and the rate of lymph node metastasis.CONCLUSION SIRI values are correlated with adverse in the gastric cancer population and have the potential to be utilized in predicting long-term oncological survival in patients who undergo robotic radical gastric cancer surgery.

Comprehensive analysis of prognostic value and immunotherapy prospect of brain cytoplasmic RNA1 in hepatocellular carcinoma

BACKGROUND The expression of brain cytoplasmic RNA1(BCYRN1)is linked to the clinicopathology and prognosis of several types of cancers,among which hepatocellular carcinoma(HCC)is one of the most frequent types of cancer worldwide.AIM To explore the prognostic value and immunotherapeutic potential of BCYRN1 in HCC by bioinformatics and meta-analysis.METHODS Information was obtained from the Cancer Genome Atlas database.First,the correlation between BCYRN1 expression and prognosis and clinicopathologic characteristics of HCC patients was explored.Univariate and multivariate regression analyses were employed to examine the relationship between BCYRN1 and HCC prognosis.Secondly,potential functions and pathways were explored by means of enrichment analysis of differentially-expressed genes.The relationships between BCYRN1 expression and tumor microenvironment,immune cell infiltration,immune checkpoint,drug sensitivity and immunotherapy effect were also investigated.Finally,three major databases were searched and used to conduct a meta-analysis on the relationship between BCYRN1 expression and patient prognosis.RESULTS BCYRN1 expression was significantly higher in HCC compared to normal tissues and was linked to a poor prognosis and clinicopathological characteristics.Enrichment analysis showed that BCYRN1 regulates the extracellular matrix and transmission of signaling molecules,participates in the metabolism of nutrients,such as proteins,and participates in tumor-related pathways.BCYRN1 expression was linked to the tumor microenvironment,immune cell infiltration,drug sensitivity and the efficacy of immunotherapy.Furthermore,the meta-analysis in this study showed that BCYRN1 overexpression was related to a worse outcome in HCC patients.CONCLUSION Overexpression of BCYRN1 relates to poor prognosis and may be a potential prognostic factor and immunotherapeutic target in HCC.

Comparison between laparoscopic uncut Roux-en-Y and Billroth Ⅱ with Braun anastomosis after distal gastrectomy:A meta-analysis

BACKGROUND Conventional Billroth Ⅱ(BⅡ) anastomosis after laparoscopic distal gastrectomy(LDG) for gastric cancer(GC) is associated with bile reflux gastritis, and Roux-enY anastomosis is associated with Roux-Y stasis syndrome(RSS). The uncut Rouxen-Y(URY) gastrojejunostomy reduces these complications by blocking the entry of bile and pancreatic juice into the residual stomach and preserving the impulse originating from the duodenum, while BⅡ with Braun(BB) anastomosis reduces the postoperative biliary reflux without RSS. Therefore, the purpose of this study was to compare the efficacy and safety of laparoscopic URY with BB anastomosis in patients with GC who underwent radical distal gastrectomy.AIM To evaluate the value of URY in patients with GC.METHODS PubMed, Embase, Web of Science, Cochrane Library, Chinese National Knowledge Infrastructure, Wanfang, Chinese Biomedical Database, and VIP Database for Chinese Technical Periodicals(VIP) were used to search relevant studies published from January 1994 to August 18, 2021. The following databases were also used in our search: Clinicaltrials.gov, Data Archiving and Networked Services, the World Health Organization International Clinical Trials Registry Platform Search Portal(https://www.who.int/clinical-trials-registry-platform/the-ictrp-search-portal), the reference lists of articles and relevant conference proceedings in August 2021. In addition, we conducted a relevant search by Reference Citation Analysis(RCA)(https://www.referencecitationanalysis.com). We cited highquality references using its results analysis functionality. The methodological quality of the eligible randomized clinical trials(RCTs) was evaluated using the Cochrane Risk of Bias Tool, and the non-RCTs were evaluated using the Newcastle-Ottawa scale. Statistical analyses were performed using Review Manager(Version 5.4).RESULTS Eight studies involving 704 patients were included in this meta-analysis. The incidence of reflux gastritis [odds ratio = 0.07, 95% confidence interval(CI): 0.03-0.19, P < 0.00001] was significantly lower in the URY group than in the BB group. The pH of the postoperative gastric fluid was lower in the URY group than in the BB group at 1 d [mean difference(MD) =-2.03, 95%CI:(-2.73)-(-1.32),P < 0.00001] and 3 d [MD =-2.03, 95%CI:(-2.57)-(-2.03), P < 0.00001] after the operation. However,no significant difference in all the intraoperative outcomes was found between the two groups.CONCLUSION This work suggests that URY is superior to BB in gastrointestinal reconstruction after LDG when considering postoperative outcomes.

Neoadjuvant chemotherapy for patients with resectable colorectal cancer liver metastases: A systematic review and meta-analysis

BACKGROUND In recent years,neoadjuvant chemotherapy(NAC)has been increasingly used in patients with resectable colorectal liver metastases.However,the efficacy and safety of NAC in the treatment of resectable colorectal liver metastases(CRLM)are still controversial.AIM To assess the efficacy and application value of NAC in patients with resectable CRLM.METHODS We searched PubMed,Embase,Web of Science,and the Cochrane Library from inception to December 2020 to collect clinical studies comparing NAC with non-NAC.Data processing and statistical analyses were performed using Stata V.15.0 and Review Manager 5.0 software.RESULTS In total,32 studies involving 11236 patients were included in this analysis.We divided the patients into two groups,the NAC group(that received neoadjuvant chemotherapy)and the non-NAC group(that received no neoadjuvant chemotherapy).The meta-analysis outcome showed a statistically significant difference in the 5-year overall survival and 5-year disease-free survival between the two groups.The hazard ratio(HR)and 95%confidence interval(CI)were HR=0.49,95%CI:0.39-0.61,P=0.000 and HR=0.4895%CI:0.36-0.63,P=0.000.The duration of surgery in the NAC group was longer than that of the non-NAC group[standardized mean difference(SMD)=0.41,95%CI:0.01-0.82,P=0.044)].The meta-analysis showed that the number of liver metastases in the NAC group was significantly higher than that in the non-NAC group(SMD=0.73,95%CI:0.02-1.43,P=0.043).The lymph node metastasis in the NAC group was significantly higher than that in the non-NAC group(SMD=1.24,95%CI:1.07-1.43,P=0.004).CONCLUSION We found that NAC could improve the long-term prognosis of patients with resectable CRLM.At the same time,the NAC group did not increase the risk of any adverse event compared to the non-NAC group.

Efficacy and safety of intraoperative radiotherapy in rectal cancer:A systematic review and meta-analysis

BACKGROUND In recent years,intraoperative radiotherapy(IORT)has been increasingly used for the treatment of rectal cancer.However,the efficacy and safety of IORT for the treatment of rectal cancer are still controversial.AIM To evaluate the value of IORT for patients with rectal cancer.METHODS We searched PubMed,Embase,Cochrane Library,Web of Science databases,and conference abstracts and included randomized controlled trials and observational studies on IORT vs non-IORT for rectal cancer.Dichotomous variables were evaluated by odds ratio(OR)and 95%confidence interval(CI),hazard ratio(HR)and 95%CI was used as a summary statistic of survival outcomes.Statistical analyses were performed using Stata V.15.0 and Review Manager 5.3 software.RESULTS In this study,3 randomized controlled studies and 12 observational studies were included with a total of 1460 patients,who are mainly residents of Europe,the United States,and Asia.Our results did not show significant differences in 5-year overall survival(HR=0.80,95%CI=0.60-1.06;P=0.126);5-year disease-free survival(HR=0.94,95%CI=0.73-1.22;P=0.650);abscess(OR=1.10,95%CI=0.67-1.80;P=0.713),fistulae(OR=0.79,95%CI=0.33-1.89;P=0.600);wound complication(OR=1.21,95%CI=0.62-2.36;P=0.575);anastomotic leakage(OR=1.09,95%CI=0.59-2.02;P=0.775);and neurogenic bladder dysfunction(OR=0.69,95%CI=0.31-1.55;P=0.369).However,the meta-analysis of 5-year local control was significantly different(OR=3.07,95%CI=1.66-5.66;P=0.000).CONCLUSION The advantage of IORT is mainly reflected in 5-year local control,but it is not statistically significant for 5-year overall survival,5-year disease-free survival,and complications.

AIWW:a new nutrition-screening tool for the oncologic population

Malnutrition is a common comorbidity among patients with cancer.However,no nutrition-screening tool has been recognized in this population.A quick and easy screening tool for nutrition with high sensitivity and easy-to-use is needed.Based on the previous 25 nutrition-screening tools,the Delphi method was made by the members of the Chinese Society of Nutritional Oncology to choose the most useful item from each category.According to these results,we built a nutrition-screening tool named age,intake,weight,and walking(AIWW).Malnutrition was defined based on the scored patient-generated subjective global assessment(PG-SGA).Concurrent validity was evaluated using the Kendall tau coefficient and kappa consistency between the malnutrition risks of AIWW,nutritional risk screening 2002(NRS-2002),and malnutrition screening tool(MST).Clinical benefit was calculated by the decision curve analysis(DCA),integrated discrimination improvement(IDI),and continuous net reclassification improvement(c NRI).A total of 11,360 patients(male,n=6,024(53.0%)were included in the final study cohort,and 6,363 patients had malnutrition based on PG-SGA.Based on AIWW,NRS-2002,and MST,7,545,3,469,and1,840 patients were at risk of malnutrition,respectively.The sensitivities of AIWW,NRS-2002,and MST risks were 0.910,0.531,and 0.285,and the specificities were 0.768,0.946,and 0.975.The Kendall tau coefficients of AIWW,NRS-2002,and MST risks were 0.588,0.501,and 0.326,respectively.The area under the curve of AIWW,NRS-2002,and MST risks were0.785,0.739,and 0.630,respectively.The IDI,c NRI,and DCA showed that AIWW is non-inferior to NRS-2002(IDI:0.002(-0.009,0.013),c NRI:-0.015(-0.049,0.020)).AIWW scores can also predict the survival of patients with cancer.The missed diagnosis rates of AIWW,NRS-2002,and MST were 0.09%,49.0%,and 73.2%,respectively.AIWW showed a better nutritionscreening effect than NRS-2002 and MST for patients with cancer and could be recommended as an alternative nutritionscreening tool for this population.

Reporting and methodological quality of meta-analyses of acupuncture for patients with migraine:A methodological investigation with evidence map

Background:Acupuncture has been widely used to relieve migraine-related symptoms.However,the findings of previous systematic reviews(SRs)and meta-analyses(MAs)are still not completely consistent.Their quality is also unknown,so a comprehensive study is needed.Objective:To evaluate the reporting and methodological quality of these MAs concerning acupuncture for migraine,and summarize evidence about the efficacy and safety of acupuncture for migraine.Search strategy:Pub Med,Embase,Cochrane Library,China National Knowledge Infrastructure,Chinese Biomedical Databases,Wanfang Data,and VIP databases were searched from inception to September 2020,with a comprehensive search strategy.Inclusion criteria:The pairwise MAs of randomized controlled trials(RCTs)concerning migraine treated by acupuncture or acupuncture-based therapies,with a control group that received sham acupuncture,medication,no treatment,or acupuncture at different acupoints were included.Data extraction and analysis:Two independent investigators screened studies,extracted relevant data,and assessed reporting and methodological quality using Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)2009 and A Measurement Tool to Assess Systematic Reviews 2(AMSTAR 2),then all results were cross-checked.Spearman correlation test was used to evaluate the correlation between reporting and methodological quality scores.Results:A total of 20 MAs were included in this study.The included MAs indicated that acupuncture was efficacious and safe in preventing and treating migraine when compared with control intervention.There was a high correlation between reporting and methodological quality scores(rs=0.87,P<0.001).The quality of the included SRs needs to be improved mainly with regard to protocol and prospective registration,using a comprehensive search strategy,summarizing the strength of evidence body for key outcomes,a full list of excluded studies with reasons for exclusion,reporting of RCTs’funding sources,and assessing the potential impact of risk of bias in RCTs on MA results.Conclusion:Acupuncture is an effective and safe intervention for preventing and treating migraine,and could be considered as a good option for patients with migraine.However,the reporting and methodological quality of MAs included in this overview is suboptimal.In the future,AMSTAR 2 and PRISMA tools should be followed when making and reporting an SR with MA.