Multiple genetic variants predict the progression-free survival of bevacizumab plus chemotherapy in advanced ovarian cancer: A retrospective study

Bevacizumab (BV) plus chemotherapy is broadly used in advanced ovarian cancer (OC). However, the efficacy of BV-based regimens for advanced OC patients is not satisfactory. Therefore, it is urgent to explore the predictive genetic biomarkers for BV.Tumor tissues from advanced OC patients receiving BV-based regimens were analyzed with a 150-gene targeted panel for next generation sequencing. The associations between gene alterations or clinicopathology features and progression-free survival (PFS) were analyzed by Kaplan–Meier curves or Cox regression. The association of the genetic alteration in potential predictive genes and expressions of 11 vascular endothelial growth factor-related genes were analyzed in The Cancer Genome Atlas cohort using 292 OC cases.Sixty two Chinese advanced OC patients treated with BV-based therapy were included. The median PFS of was 6.9 months, and objective response rate was 14.5%. In multivariate Cox regression analysis, the status of endothelial growth factor receptor (EGFR) (hazard ratio = 6.39, 95% confidence interval [CI] 2.25–18.13, P < .001) and human epidermal growth factor receptor 2 (HER2) (hazard ratio = 3.58, 95% CI 1.27–10.08, P = .016) were significantly correlated with PFS. MYC Proto-Oncogene amplification seemed to have a positive trend (hazard ratio = 0.21, 95% CI 0.05–1.02, P = .052). Moreover, EGFR and HER2 alterations were not prognostic factors of overall survival for OC in The Cancer Genome Atlas OC cohort. The vascular endothelial growth factor-related signature analysis indicated vascular endothelial factor A expression was upregulated with EGFR alterations (P = .034) which may be involved in BV resistance, and HER2 alterations were associated with hypoxia inducible factor 1 subunit alpha overexpression significantly (P = .029).EGFR or HER2 alterations are negative predictors of PFS for OC patient treated with BV plus chemotherapy. Therefore, the clinicians may consider to use alternative regimens such as anti-EGFR or anti-HER2 targeted therapy instead of BV-based regimens on these patients when standard care fail.     

The predictive and prognostic effects of PD-L1 expression on TKI treatment and survival of EGFR-mutant NSCLC: A meta-analysis

Whether programmed death-ligand 1 (PD-L1) expression could predict the outcome of tyrosine kinase inhibitor (TKI) treatment and prognosis of epidermal growth factor receptor (EGFR)-mutant nonsmall cell lung cancer (NSCLC) is remaining controversial.Potential studies were search from PubMed, Embase, and Web of Science databases. Pooled odds ratio of objective response rate was used to describe the relationship between PD-L1 expression and primary resistance to EGFR-TKIs. Pooled hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS) were included to assess the effects of PD-L1 status on the outcome of EGFR-TKI treatment and survival of EGFR-mutant NSCLCs.Eighteen eligible studies (1986 EGFR-mutant NSCLCs) were included in this meta-analysis. Positive PD-L1 expression correlated with lower objective response rate of EGFR-TKI treatment (odds ratio [95% confidence interval {CI}] = 0.52 [0.28–0.98], P = .043), while PFS (adjusted HR [95% CI] = 1.49 [0.96–1.89], P = .332) and OS (HR [95% CI] = 1.24 [0.70–2.20], P = .456) of EGFR-TKI treatment did not correlated with PD-L1 status. Furthermore, PD-L1 expression was not a predictive biomarker for the OS (HR [95% CI] = 1.43 [0.98–2.08], P = .062) in overall EGFR-mutant cohort.Positive PD-L1 expression indicated a higher incidence of primary resistance, but did not correlate with the PFS or OS of EGFR-TKI therapy. In addition, PD-L1 expression was unlikely a predictive biomarker for prognosis of EGFR-mutant NSCLCs.     

Prognostic Value of Plasma Epstein–Barr Virus DNA for Local and Regionally Advanced Nasopharyngeal Carcinoma Treated With Cisplatin-Based Concurrent Chemoradiotherapy in Intensity-Modulated Radiotherapy Era

This study aimed to evaluate the prognostic value of plasma Epstein–Barr Virus DNA (EBV DNA) for local and regionally advanced nasopharyngeal carcinoma (NPC) patients treated with concurrent chemoradiotherapy in intensity-modulated radiotherapy (IMRT) era.In this observational study, 404 nonmetastatic local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy were recruited. Blood samples were collected before treatment for examination of plasma EBV DNA levels. We evaluated the association of pretreatment plasma EBV DNA levels with progression-free survival rate (PFS), distant metastasis-free survival rate (DMFS), and overall survival rate (OS).Compared to patients with an EBV DNA level <4000 copies/mL, patients with an EBV DNA ≥4000 copies/mL had a lower rate of 3-year PFS (76%, 95% CI [68–84]) versus (93%, 95% CI [90–96], P < 0.001), DMFS (83%, 95% CI [76–89]) versus (97%, 95% CI [94–99], P < 0.001), and OS (85%, 95% CI [78–92]) versus (98%, 95% CI [95–100], P < 0.001). Multivariate analysis showed that pretreatment EBV DNA levels (HR = 3.324, 95% CI, 1.80–6.138, P < 0.001) and clinical stage (HR = 1.878, 95% CI, 1.036–3.404, P = 0.038) were the only independent factor associated with PFS, pretreatment EBV DNA level was the only significant factor to predict DMFS (HR = 6.292, 95% CI, 2.647–14.956, P < 0.001), and pretreatment EBV DNA levels (HR = 3.753, 95% CI, 1.701–8.284, P < 0.001) and clinical stage (HR = 2.577, 95% CI, 1.252–5.050, P = 0.010) were significantly associated with OS. In subgroup analysis, higher plasma EBV DNA levels still predicted a worse PFS, DMFS, and OS for the patients stage III or stage IVa-b, compared with those with low EBV DNA levels.Elevated plasma EBV DNA was still effective prognostic biomarker for local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy. Future ramdomized clinical trials are needed to further evaluate whether plasma EBV DNA levels could be applied to guide concurrent chemotherapy regimen for local and regionally advanced NPC patients.     

Anti-EGFR monoclonal antibody plus chemotherapy for treating advanced non-small cell lung cancer: A meta-analysis

Background:The use of standard cytotoxic chemotherapy seems to have reached a “treatment plateau”. The application of anti-epidermal growth factor receptor (EGFR) monoclonal antibodies (mAbs) is a new strategy for non-small-cell lung cancer (NSCLC) therapy. We aimed to comprehensively assess the efficacy and safety of anti-EGFR-mAbs plus chemotherapy as first-line therapy for advanced NSCLC.Methods:According to inclusion and exclusion criteria, we conducted a comprehensive literature search of electronic databases. From the included trials, information on overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse events (AEs) was extracted.Results:The research showed that compared with chemotherapy alone, anti-EGFR-mAb plus chemotherapy combinations significantly improved OS (HR = 0.88, 95%CI: 0.83-0.94, P < .0001), PFS (HR = 0.89, 95%CI: 0.83-0.95, P = 0.0004) and ORR (OR = 1.39, 95%CI: 1.13-1.69, P = .001). Meta subgroup analyses manifested that the OS of patients with squamous NSCLC treated with anti-EGFR-mAb plus chemotherapy combinations was notably better than that of patients with non-squamous NSCLC treated with the same combinations (HR = 0.82, 95%CI: 0.73-0.92, P = .0005). Compared with the chemotherapy group, combination of chemotherapy and anti-EGFR mAb showed increase in incidences of severe AEs (> = grade 3) that mainly include, leukopenia (OR = 1.53, 95%CI: 1.28-1.82, P < .00001), febrile neutropenia (OR = 1.35, 95%CI: 1.06-1.71, P = .02), hypomagnesemia (OR = 5.68, 95%CI: 3.54-9.10, P < .00001), acneiform rash (OR = 35.88, 95%CI: 17.37-74.10, P < .00001), fatigue (OR = 1.24, 95%CI: 1.02-1.49, P = .03), diarrhea (OR = 1.69, 95%CI: 1.16-2.47, P = .006), and infusion-related reactions (OR = 3.78, 95%CI: 1.93-7.41, P = .0001).Conclusion:Adding an anti-EGFR-mAb to the standard platinum-based chemotherapy regimens used for the first-line treatment of advanced NSCLC resulted in statistically notable improvements in OS, PFS, and ORR. In particular, anti-EGFR-mAb and chemotherapy combinations achieved greater survival benefits in patients with squamous NSCLC than in those with non-squamous NSCLC. In addition, the safety profile of chemotherapy plus anti-EGFR-mAb combinations was acceptable compared to that of chemotherapy alone.     

The relationship between NLR/PLR/LMR levels and survival prognosis in patients with non-small cell lung carcinoma treated with immune checkpoint inhibitors

Background:The relationship between neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) and the dire prognosis of non-small cell lung carcinoma patients who received immune checkpoint inhibitors (ICIs) are not known yet.Methods:We screened the articles that meet the criteria from the database. The relationship between NLR/PLR/LMR levels and the survival and prognosis of non-small cell lung cancer patients treated with ICIs was analyzed. Summarize hazard ratio (HR) with 95% confidence interval (CI) to study progression-free survival (PFS) and overall survival (OS).Results:Thirty-four studies involving 3124 patients were enrolled in the final analysis. In short, high pre-treatment NLR was related to poor OS (HR = 2.13, 95% CI:1.74–2.61, P < .001, I² = 83.3%, P < .001) and PFS (HR = 1.77, 95% CI:1.44–2.17, P < .001, I² = 79.5%, P < .001). Simultaneously, high pre-treatment PLR was related to poor OS (HR = 1.49, 95% CI:1.17–1.91, P < .001, I² = 57.6%, P = .003) and PFS (HR = 1.62, 95% CI:1.38–1.89, P < .001, I² = 47.1%, P = .036). In all subgroup analysis, most subgroups showed that low LMR was related to poor OS (HR = 0.45, 95% CI: 0.34–0.59, P < .001) and PFS (HR = 0.60, 95% CI: 0.47–0.77, P < 0.001, I² = 0.0%, P < .001).Conclusion:High pre-treatment NLR and pre-treatment PLR in non-small cell lung carcinoma patients treated with ICIs are associated with low survival rates. Low pre-treatment and post-treatment LMR are also related to unsatisfactory survival outcomes. However, the significance of post-treatment NLR and post-treatment PLR deserve further prospective research to prove.     

Plasma Epstein–Barr Viral Deoxyribonucleic Acid Predicts Worse Outcomes in Pediatric Nonmetastatic Nasopharyngeal Carcinoma Patients: An Observational Study of 89 Cases in an Endemic Area

To evaluate the clinical significance of pretreatment levels of plasma Epstein–Barr virus DNA (pEBV DNA) on prognoses in pediatric nasopharyngeal carcinoma (NPC) patients.Eighty-nine patients aged 21 years old or younger with nonmetastatic NPC were evaluated to determine the effect of pEBV DNA levels on progression-free survival (PFS), distant metastasis-free survival (DMFS), and overall survival (OS). Survival probabilities in patient groups that were segregated by clinical stage or pEBV DNA load (low or high) were compared.The median pretreatment concentrations of pEBV DNA were 3440 copies/mL in 35 patients with stage III disease and 14,900 copies/mL in 50 patients with stage IV disease (P = 0.059). The median concentration of pEBV DNA was 34,500 copies/mL in 17 patients with relapse, which was higher than the concentration in 72 patients without relapse, who had a median level of 4985 copies/mL (P = 0.057). Further study showed that pretreatment pEBV DNA load was an independent prognostic indicator in pediatric NPC patients. High pEBV DNA was associated with adverse clinical outcomes, including PFS [3-year PFS rate = 80.5% versus 95.8%, hazard ratio (HR) = 5.00, 95% confidence interval (CI) = 1.00–25.00; P = 0.050], DMFS (3-year DMFS rate = 80.5% versus 95.8%, HR = 5.20, 95% CI = 1.04–26.00; P = 0.045), and OS (3-year OS rate = 82.9% versus 95.8%, HR = 5.41, 95% CI = 1.08–27.22; P = 0.040).Pretreatment pEBV DNA load was an independent prognostic indicator for PFS, DMFS, and OS in pediatric patients with NPC. Prospective studies, however, are needed to validate these results.     

The prognostic value of lncRNA AGAP2-AS1 in cancer patients: A meta-analysis

Background:ArfGAP with GTPase domain, Ankyrin repeat and PH domain 2 Antisense 1 (AGAP2-AS1) is a promising long noncoding RNA that may possess prognostic value for different types of tumors. The objective of this meta-analysis is to evaluate the prognostic value of long noncoding RNA AGAP2-AS1 in cancer patients.Methods:A systematic literature search of the PubMed, Cochrane Library, EMBASE, Medline, Web of Science, CNKI, Weipu, and Wanfang electronic databases were carried out in this meta-analysis. Synthetic hazard ratios (HRs) or odd ratios (ORs) with 95% confidence intervals (CIs) were obtained to determine the prognostic and clinicopathological significance of AGAP2-AS1 expression in tumors.Results:The final meta-analysis included 10 studies that contained 948 patients. The pooled results provided evidence that AGAP2-AS1 overexpression predicted reduced overall survival (OS) (HR = 1.77, 95% CI: 1.49–2.09, P < .00001), disease-free survival (HR = 1.84, 95% CI: 1.40–2.41, P < .0001), and progression-free survival (HR = 1.84, 95% CI: 1.01–3.33, P = .04) and for various cancers. Additionally, the AGAP2-AS1 overexpression was concerned with lymph node metastasis (positive vs negative, OR = 2.95, 95% CI: 1.96–4.45, P < .00001), advanced tumor node metastasis stage (III/IV vs I/II, OR = 3.73, 95% CI: 2.71–5.13, P < .00001), and tumor size (larger vs smaller, OR = 2.28, 95% CI: 1.24–4.18, P = .008). Besides, data from gene expression profiling interactive analysis dataset verified the results in our meta-analysis. The results showed that the expression level of AGAP2-AS1 was higher in most tumor tissues than in the corresponding normal tissues and was linked to poor OS and disease-free survival.Conclusions:Our results indicated that AGAP2-AS1 overexpression was closely correlated with shorter OS in multiple cancer types, suggesting that AGAP2-AS1 might function as a promising predictor for clinical outcomes in cancer.     

Prognostic and clinicopathological significance of miR-638 in cancer patients: A meta-analysis

Introduction:MiR-638 is believed to be involved in human cancers. However, the prognostic value of miR-638 in human carcinomas is controversial and inconclusive. Therefore, we conducted this meta-analysis to investigate the association between miR-638 expression and clinical outcomes in the patients with various cancers.Methods:We searched Pubmed, Embase, Wanfang, and the China National Knowledge Infrastructure (CNKI) up to September 1, 2020 to identify relevant studies. Hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were used to correlate expression of miR-638 with prognosis and clinicopathological features.Results:A total of 18 studies involving 1886 patients were included in the meta-analysis. The results revealed that low miR-638 expression was significantly correlated with poor overall survival (OS) (HR = 2.09, 95% CI: 1.46–2.98, P < .001), but not with disease-free survival (DFS) (HR = 1.71, 95% CI: 0.31–9.56, P = .540). Subgroup analysis found that low miR-638 expression was associated with worse OS in patients with digestive system cancer (HR = 2.47, 95% CI: 1.85–3.30, P < .001), the reported directly from articles group (HR = 2.12, 95% CI: 1.34–3.33, P < .001), survival curves group (HR = 2.02, 95% CI: 1.07–3.80, P = .029), in studies with sample size ≥100 (HR = 2.12, 95% CI: 1.34–3.35, P = .001), and in studies with sample size <100 (HR = 2.02, 95%CI: 1.09–3.75, P = .025). Moreover, cancer patients with low miR-638 expression were prone to tumor size (OR = 1.47, 95% CI: 1.03–2.09, P = .035), earlier lymph node metastasis (present vs absent, OR = 2.26, 95% CI: 1.63–3.14, P < .001), earlier distant metastasis (present vs absent, OR = 2.60, 95% CI: 1.45–4.67, P < .001), TNM stage (III-IV vs I-II, OR = 2.01, 95% CI: 1.35–2.99, P = .001), and portal vein invasion (present vs absent, OR = 4.39, 95% CI:2.23–8.64, P < .001), but not associated with age, gender, tumor differentiation, and vascular invasion.Conclusions:MiR-638 may serve as a promising indicator in the prediction of prognosis and clinicopathological features in patients with different kinds of cancers.     

Prognostic significance of ANO1 expression in cancers

Background:Anoctamin-1 (ANO1) plays a pivotal role in cancer progression. A meta-analysis was conducted to assess the potential prognostic role of ANO1 in cancers.Methods:A total of 1760 patients from 7 eligible studies were included into the analysis. Pooled hazard ratios or odds ratios were extracted and calculated with a random-effects model, and analyses of heterogeneity bias were conducted.Results:Our results showed that over expression of ANO1 was significantly correlated with poor overall survival in all cancers (HR = 1.52; 95% CI: 1.19–1.92; P = .0006). Subgroup analysis indicated that there was a significant association between over expression of ANO1 and poor prognosis breast cancer (HR = 3.24; 95% CI: 1.74–6.04), head and neck squamous cell carcinoma (HR = 1.14; 95% CI: 1.00–1.30), esophageal squamous cell carcinoma (HR = 1.93; 95% CI: 1.07–3.50), gastric cancer (HR = 1.62; 95% CI: 1.12–2.34) and colorectal cancer (HR = 1.38; 95% CI: 1.03–1.85). In addition, over expression of ANO1 was not associated with TNM stage, histological grade, lymph node metastasis, tumor size, age and gender. However, ANO1 was significantly associated with human epidermal growth factor receptor 2, but not associated with progesterone receptor or estrogen receptor in breast cancer.Conclusions:Our results indicate that ANO1 can be a predictive factor for prognosis of cancer.     

Association between Alpha B-crystallin expression and prognosis in patients with solid tumors: A protocol for systematic review and meta-analysis

Background:Alpha B-crystallin (CRYAB), as a small heat shock protein, may play critical roles in the tumorigenesis and progression of several kinds of human cancers. However, the prognostic value of CRYAB in solid malignancies remains controversial. The aim of the present study was to investigate the association between CRYAB expression and clinicopathology and prognosis of solid tumor patients.Methods:PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure, and WanFang databases were systematically searched to retrieve studies that investigated the prognostic value of CRYAB expression in various solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to determine the strength of association between CRYAB expression and survival in patients with solid tumors. Odds ratios (ORs) with 95% CIs were pooled to assess the correlation between CRYAB expression and clinicopathological characteristics of patients with solid tumors.Results:A total of 17 studies, including 18 cohorts with 6000 patients, were included in this meta-analysis. Our results showed that increased CRYAB expression could predict poor overall survival (HR = 1.81, 95% CI: 1.50–2.19, P < .001), disease-free survival (HR = 1.47, 95% CI: 1.16–1.86, P = .001), and disease-specific survival (HR = 1.40, 95% CI: 1.19–1.63, P < .001) in patients with cancer. Furthermore, the high expression level of CRYAB was associated with certain phenotypes of tumor aggressiveness, such as lymph node metastasis (OR = 2.46, 95% CI: 1.48–4.11, P = .001), distant metastasis (OR = 3.34, 95% CI: 1.96–5.70, P < .001), advanced clinical stage (OR = 2.24, 95% CI: 1.24–4.08, P = .008), low OS rate (OR = 4.81, 95% CI: 2.82–8.19, P < .001), and high recurrence rate (OR = 1.38, 95% CI: 1.11–1.72, P = .004).Conclusions:CRYAB may serve as a valuable prognostic biomarker and therapeutic target in human solid tumors.     

Prognostic role of tripartite motif containing 24 in various human solid malignant neoplasms: An updated meta-analysis and systematic review

Background:Currently, clinical studies of tripartite motif containing 24 (TRIM24) on human solid malignant neoplasms were developing, but the prognosis value of TRIM24 continues to be controversial. The aim of our study is to explore the prognostic effect of TRIM24 in various human solid malignant neoplasms.Methods:We performed a comprehensive research for eligible studies which evaluated the prognostic roles of TRIM24 in cancer patients based on PubMed, Embase, Web of Science, and China National Knowledge Infrastructure. The hazard ratios (HRs) with 95% confidence intervals (CIs) for various malignances were extracted from eligible studies.Results:A total of 13 studies with 1909 patients were enrolled in this analysis. Combined analyses showed that high expression of TRIM24 significantly predicted poorer overall survival both in univariate analysis (HR = 1.61, 95% CI 1.21–2.15, P = .001) and multivariate analysis (HR = 2.19, 95% CI 1.10–4.38, P = .026). In stratified analyses, high TRIM24 expression level predicted even worse overall survival in hormone-related cancers (HR = 1.92, 95% CI 1.28–2.86, P = .001). Although, expression of TRIM24 failed to show a significant relation with progression-free survival/disease-free survival/recurrence-free survival (HR = 1.42, 95% CI 0.93–2.16, P = .106), high expression predicted significant worse progression-free survival/disease-free survival/recurrence-free survival in hormone-related cancer (HR = 1.71, 95% CI 1.12–2.59, P = .013).Conclusion:TRIM24 could serve as a new biomarker for patients with solid malignancies and could be a potential therapeutic target for patients especially for patients with hormone-related malignancies.     

Pooled-analysis of efficacy and safety of minimally invasive versus standard percutaneous nephrolithotomy

Background:This study aimed to assess the efficacy and safety of minimally invasive percutaneous nephrolithotomy (MPCNL) versus standard percutaneous nephrolithotomy in patients with renal and upper ureteric stones.Methods:We conducted a pooled analysis on randomized controlled trials (RCTs). The eligible RCTs were selected from the following databases: MEDLINE, Embase, Web of Science, and the Cochrane Library. The reference lists of retrieved studies were also investigated.Results:Our analysis included 10 RCTs with 1612 patients. Pooled data from 10 RCTs revealed the following: stone-free rate (odds ratio = 1.46, 95% confidence interval (CI) [1.12,1.88], P = .004), operative time (mean difference [MD]  = 4.10, 95% CI [–1.37,9.56], P = .14), length of hospital stay (MD = –15.31, 95% CI [–29.43,–1.19], P = .03), hemoglobin decrease (MD = –0.86, 95% CI [–1.19,–0.53], P < .00001), postoperative fever (MD = 0.83, 95% CI [0.49,1.40], P = .49), and urine leakage (MD = 0.59, 95% CI [0.25,1.37], P = .22). Besides, we performed sub-group analysis based on vacuum suction effect and multiple kidney stones. For vacuum suction effect, it revealed the following: stone-free rate in vacuum suction group (P = .007) and in non-vacuum suction group (P = .19). Operative time in vacuum suction group (P = .89), non-vacuum suction group (P = .16). Postoperative fever in vacuum suction group (P = .49), non-vacuum suction group (P = .85).Conclusion:This pooled analysis indicated that MPCNL was a safe and effective method for treating renal stones compared with standard percutaneous nephrolithotomy. Besides, the vacuum suction effect in MPCNL played a more important role. When it comes to multiple or staghorn stones, the longer operative time in MPCNL could not be ignored.     

Efficacy and safety of PD-1/PD-L1 inhibitors combined with CTLA-4 inhibitor versus chemotherapy for advanced lung cancer: A meta-analysis

Background:This meta-analysis was performed to compare efficacy and tolerability between antiprogrammed cell death (PD-1)/programmed cell death-ligand-1 (PD-L1) + anticytotoxic T-lymphocyte-associated protein-4 (CTLA-4) treatment and chemotherapy in advanced lung cancer.Methods:Cochrane Library, Embase, and PubMed databases were searched for potential articles. The fixed-effect model or random-effect model was adopted for pooled analysis based on the I² and P-value.Results:Six articles with 1338 patients were identified and subjected to meta-analysis. Compared with chemotherapy, anti-PD-1/PD-L1 + anti-CTLA-4 treatment could significantly improve the overall survival (hazard ratio [HR] = 0.78, 95%confidence interval [CI]: 0.71–0.84, P = .21) and progression-free survival (HR = 0.77, 95%CI: 0.71–0.83, P = .30) of advanced lung cancer patients. Moreover, there was no obvious difference in the incidence of 3 to 4 adverse events (AEs) serious adverse reactions (HR = 1.35, 95%CI: 0.66–2.74, P < .00001) between the 2 treatment groups, but the incidence rates of AEs leading to discontinuation (HR = 2.56, 95%CI: 1.53–4.30, P < .00001) and AEs leading to death (HR = 2.10, 95%CI: 1.21–3.63, P = .20) were higher. Furthermore, no remarkable differences in objective response rate (HR = 1.31, 95%CI: 0.97–1.77, P = .02) were observed between the 2 groups.Conclusion:Our meta-analysis revealed that PD-1/PD-L1 inhibitors plus CTLA-4 inhibitor could markedly improve the endpoint outcomes of patients compared with chemotherapy alone, and did not significantly increase the serious adverse reactions. Thus, it can serve as a new treatment strategy for advanced lung cancer.     

The effect of glucocorticoids on mortality in severe COVID-19 patients: Evidence from 13 studies involving 6612 cases

Background:Since the start of the coronavirus disease 2019 (COVID-19) pandemic, there is an urgent need for effective therapies for patients with COVID-19. In this study, we aimed to assess the therapeutic efficacy of glucocorticoids in severe COVID-19.Methods:A systematic literature search was performed across PubMed, Web of Science, EMBASE, and the Cochrane Library (up to June 26, 2021). The literature investigated the outcomes of interest were mortality and invasive mechanical ventilation.Results:The search identified 13 studies with 6612 confirmed severe COVID-19 patients. Our meta-analysis found that using glucocorticoids could significantly decrease COVID-19 mortality (hazard ratio (HR) 0.60, 95% confidence interval (CI) 0.45–0.79, P < .001), relative to non-use of glucocorticoids. Meanwhile, using glucocorticoids also could significantly decrease the risk of progression to invasive mechanical ventilation for severe COVID-19 patients (HR = 0.69, 95% CI 0.58–0.83, P < .001). Compared with using dexamethasone (HR = 0.68, 95% CI 0.50–0.92, P = .012), methylprednisolone use had a better therapeutic effect for reducing the mortality of patients (HR = 0.35, 95% CI 0.19–0.64, P = .001).Conclusion:The result of this meta-analysis showed that using glucocorticoids could reduce mortality and risk of progression to invasive mechanical ventilation in severe COVID-19 patients.     

Association of the VEGFR2 single nucleotide polymorphism rs2305948 with glioma risk

Background:Many studies have reported a relationship between the vascular endothelial growth factor receptor 2 single nucleotide polymorphism (SNP) rs2305948 and glioma, but their conclusions have been controversial. A meta-analysis was performed to assess the association between rs2305948 and glioma susceptibility.Methods:Inclusion criteria and a strategy for screening of original literature were created. Eligible articles on the correlation between the SNP rs2305948 and glioma were identified in the PubMed, Embase, Web of Science, Cochrane Library, CNKI and Wanfang databases. After extracting the data, Stata 12. 0 software was used to perform statistical analysis under 5 genetic models and to calculate the combined odds ratio (OR) value and its 95% confidence interval (CI).Results:Four case-control studies including 1595 cases and 1657 controls were entered into the study. The overall analysis showed that no obvious association existed between rs2305948 and glioma risk (allele: OR = 1.20, 95% CI = 0.93–1.54, P = .162; dominant: OR = 1.17, 95% CI = 0.93–1.46, P = .174; recessive: OR = 1.72, 95% CI = 0.94–3.15, P = .076; heterozygous: OR = 1.11, 95% CI = 0.94–1.30, P = .226; homozygous: OR = 1.74, 95% CI = 0.92–3.29, P = .088). The subgroup analysis suggested that the SNP rs2305948 was related to glioma susceptibility under allele, dominant, recessive and homozygote models in the Asian population (allele: OR = 1.34, 95% CI = 1.16–1.55, P < .001; recessive: OR = 2.24, 95% CI = 1.49–3.36, P < .001; homozygous: OR = 2.32, 95% CI = 1.54–3.50, P < .001).Conclusion:The vascular endothelial growth factor receptor 2 rs2305948 gene polymorphism may be related to glioma susceptibility in the Asian population. However, the association is not clear in non-Asian populations, for which there has been less research.     

LKB1 expression and the prognosis of lung cancer: A meta-analysis

Background:In the past few decades, many lines of evidence implicate the importance of liver kinase B1 (LKB1) as a tumor suppressor gene in the development and progression of solid tumours. However, the prognostic and clinicopathological value of LKB1 in patients with lung cancer are controversial. This article aimed to investigate the latest evidence on this question.Methods:A systematic literature searched in the PubMed, Web of Science, Embase, Cochrane library, Scopus until September 20, 2020. The association between overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), clinicopathological features and LKB1 were analysed by meta-analysis.Results:Eleven studies including 1507 patients were included in this meta-analysis. The pooled results revealed that low LKB1 expression was significantly associated with poor overall survival (OS) (HR = 1.67, 95% CI: 1.07–2.60, P = .024) in lung cancer. However, no association was found between LKB1 expression and DFS/PFS (HR = 1.29, 95% CI: 0.70–2.39, P = .410). Pooled results showed that low LKB1 expression was associated with histological differentiation (poor vs moderate or well, OR = 4.135, 95% CI:2.524–6.774, P < .001), nodal metastasis (absent vs present, OR = 0.503, 95% CI: 0.303–0.835, P = .008) and smoking (yes vs no, OR = 1.765, 95% CI: 1.120–2.782, P = .014).Conclusion:These results suggest that low expression of LKB1 can be considered as a unfavorable prognostic biomarker for human lung cancer, which should be further researched.     

Prognostic significance of A-kinase interacting protein 1 expression in various cancers: A meta-analysis based on the Chinese population

Background:Cumulative evidence suggests that A-kinase interacting protein 1 (AKIP1) plays an important role in tumor progression. However, the prognostic value of AKIP1 expression in various cancers remains unclear. Here, we conducted a meta-analysis to evaluate the prognostic value of AKIP1 expression in patients with cancer.Methods:The PubMed, Web of Science, EMBASE, CNKI, and Wanfang databases were systematically searched to identify studies in which the effect of AKIP1 expression on prognosis (overall survival or disease-free survival) was investigated. Hazard ratios (HRs) with 95% confidence intervals (CIs) were combined to assess the effect of AKIP1 expression on patient survival. Odds ratios (ORs) with 95% CIs were pooled to estimate the association between AKIP1 expression and clinicopathological characteristics of patients with cancer.Results:Nineteen eligible studies, encompassing 3979 patients, were included in the meta-analysis. AKIP1 expression was negatively associated with overall survival (HR = 1.86, 95% CI: 1.58–2.18, P < .001) and disease-free survival (HR = 1.69, 95% CI: 1.53–1.87, P < .001) in patients with cancer. Moreover, AKIP1 overexpression was positively correlated with adverse clinicopathological features, such as tumor size (OR = 2.22, 95% CI: 1.67–2.94, P < .001), clinical stage (OR = 2.05, 95% CI: 1.45–2.90, P < .001), depth of tumor invasion (OR = 2.98, 95% CI: 2.21–4.02, P < .001), and degree of lymph node metastasis (OR = 2.12, 95% CI: 1.75–2.57, P < .001).Conclusions:High AKIP1 expression is an unfavorable prognostic biomarker and may serve as a potential therapeutic target in patients with cancer.     

Overexpression of macrophage-colony stimulating factor-1 receptor as a prognostic factor for survival in cancer: A systematic review and meta-analysis

Background:The relation between the expression of macrophage-colony stimulating factor-1 receptor (CSF-1R) and prognosis of cancer patients has been evaluated in multiple studies, but the results remain controversial. We, therefore, performed a meta-analysis and systematic review to figure out the role of CSF-1R in the prognosis of patients with cancer.Methods:Several databases were searched, including Web of Science, PubMed, and EMBASE. All human studies were published as full text. The Newcastle–Ottawa risk of bias scale was applied to evaluate the research. We extracted hazard ratios (HRs) with 95% confidence interval (95% CI) which assessed progression-free survival (PFS) and overall survival (OS) in order to assess the impacts of CSF-1R on the prognosis of cancer patients.Results:A total of 12 citations were identified, with studies including 2260 patients in different cancer types that met the eligibility criteria. It was suggested in a pooled analysis that the over-expression of CSF-1R was significantly related to worse PFS (HR: 1.68; P < .001, 1.25–2.10, 95% CI) and also poorer OS (HR=1.28; P < .001, 1.03–1.54, 95% CI). Analysis in subgroups indicated over-expressed CSF-1R was significantly associated with worse OS in hematological malignancy (HR = 2.29; P < .001, 1.49–3.09, 95% CI; model of fixed-effects; I² = 0.0%, P < .001). Sensitivity analysis suggested that there was no study influencing the stability of the results.Conclusions:The overexpression of CSF-1R was significantly predictive of worse prognosis in those who suffer from different kinds of malignancies, particularly in hematological malignancy, which indicates that it might be a potential biomarker of prognosis in cancer survival and a potential molecular target in the treatment of malignant tumors.     

Efficacy and safety of sacubitril-valsartan in patients with heart failure: a systematic review and meta-analysis of randomized clinical trials: A PRISMA-compliant article

Background:To investigate the efficacy and safety of sacubitril-valsartan in patients with heart failure, relevant randomized clinical trials (RCTs) were analyzed.Methods:We used Cochrane Library, PubMed web of science, CNKI, VIP, Medline, ISI Web of Science, CBMdisc, and Wanfang database to conduct a systematic literature research. A fixed-effects model was used to evaluate the standardized mean differences (SMDs) with 95% confidence intervals. We conducted sensitivity analysis and analyzed publication bias to comprehensively estimate the efficacy and safety of sacubitril-valsartan in patients with heart failure.Results:Among 132 retrieved studies, 5 relevant RCTs were included in the meta-analysis. The result showed that left ventricular ejection fraction (LVEF) was improved after sacubitril-valsartan in patients with heart failure, with an SMD (95% CI of 1.1 [1.01, 1.19] and P < .00001 fixed-effects model). Combined outcome indicators showed that, combined outcome indicators showed that, compared with control group, the left ventricular volume index (LAVI) (WMD = −2.18, 95% CI [−3.63, −0.74], P = .003), the E/e’ (WMD = −1.01, 95% CI [−1.89, −0.12], P = .03), the cardiovascular death (RR = 0.89, 95% CI [0.83, 0.96], P = .003], and the rehospitalization rate of heart failure (RR = 0.83, 95% CI [0.78, 0.88], P < .01) decreased more significantly, but it had no effect on renal function (WMD = 0.74, 95% CI [0.54, 1.01], P = .06).Conclusions:The present meta-analysis suggested that sacubitril-valsartan may improve the cardiac function of heart failure. Given the limited number of included studies, additional large sample-size RCTs are required to determine the long-term effect of cardiac function of sacubitril-valsartan in patients with heart failure.