Comparative Efficacy and Safety of 11 Drugs as Therapies for Adults With Neuropathic Pain After Spinal Cord Injury: A Bayesian Network Analysis Based on 20 Randomized Controlled Trials.

Objective: To provide an updated analysis of the efficacy and safety of drugs for the management of neuropathic pain (NP) after spinal cord injury (SCI) based on Bayesian network analysis. Methods: A Bayesian network meta-analysis of literature searches within PubMed, Cochrane Library, Embase, and Web of Science databases from their inception to February 21 2021 was conducted without language restrictions. Paired and network meta-analyses of random effects were used to estimate the total standardized mean deviations (SMDs) and odds ratios (ORs). Results: A total of 1,133 citations were identified and 20 RCTs (including 1,198 patients) involving 11 drugs and placebos for post-SCI NP selected. The 5 outcomes from all 11 drugs and placebos had no inconsistencies after Bayesian network analysis. BTX-A gave the most effective pain relief for the 4 weeks, following a primary outcome. No significant differences were found among drugs with regard to adverse events of the primary outcome. Gabapentin, BTX-A, and pregabalin were found to be the most helpful in relieving secondary outcomes of mental or sleep-related symptoms with differences in SMDs, ranging from -0.63 to -0.86. Tramadol triggered more serious adverse events than any of the other drugs with differences in ORs ranging from 0.09 to 0.11. Conclusion: BTX-A, gabapentin, pregabalin, amitriptyline, ketamine, lamotrigine, and duloxetine were all effective for NP management following SCI. Lamotrigine and gabapentin caused fewer side effects and had better efficacy in relieving mental or sleep-related symptoms caused by SCI-related NP. Tramadol, levetiracetam, carbamazepine, and cannabinoids could not be recommended due to inferior safety or efficacy. Systematic Review Registration: [https://inplasy.com/inplasy-2020-7-0061/], identifier [INPLASY202070061].

Heterogeneity of tumor-infiltrating myeloid cells in era of single-cell genomics.

Tumor microenvironment (TME) is highly heterogeneous and composed of complex cellular components, including multiple kinds of immune cells. Among all immune cells in TME, tumor-infiltrating myeloid cells (TIMs) account for a large proportion and play roles as key regulators in a variety of functions, ranging from immune-mediated tumor killing to tumor immune evasion. Understanding the heterogeneity of TIMs will provide valuable insights for new therapeutic targeting of myeloid cells. Single-cell genomic technologies deciphering cell composition and gene expression at single-cell resolution have largely improved our understanding of the cellular heterogeneity of TIMs and highlighted several novel cell subtypes contributing to the variation of patient survival and treatment response. However, these cell subtypes were defined based on limited data without a concordant nomenclature, which makes it difficult to understand whether they exist in different studies. Thus, in this review, we comprehensively summarized the common agreements and current different opinions on the heterogeneity of TIMs gained from single-cell studies; evaluated the feasibility of current myeloid cell targets at single-cell level and proposed a uniform nomenclature for TIM subsets.

Interrogation of the microenvironmental landscape in spinal ependymomas reveals dual functions of tumor-associated macrophages.

Spinal ependymomas are the most common spinal cord tumors in adults, but their intratumoral cellular heterogeneity has been less studied, and how spinal microglia are involved in tumor progression is still unknown. Here, our single-cell RNA-sequencing analyses of three spinal ependymoma subtypes dissect the microenvironmental landscape of spinal ependymomas and reveal tumor-associated macrophage (TAM) subsets with distinct functional phenotypes. CCL2+ TAMs are related to the immune response and exhibit a high capacity for apoptosis, while CD44+ TAMs are associated with tumor angiogenesis. By combining these results with those of single-cell ATAC-sequencing data analysis, we reveal that TEAD1 and EGR3 play roles in regulating the functional diversity of TAMs. We further identify diverse characteristics of both malignant cells and TAMs that might underlie the different malignant degrees of each subtype. Finally, assessment of cell-cell interactions reveal that stromal cells act as extracellular factors that mediate TAM diversity. Overall, our results reveal dual functions of TAMs in tumor progression, providing valuable insights for TAM-targeting immunotherapy.

Innate immune cells in the tumor microenvironment.

The tumor immune microenvironment (TIME) is a complex ecosystem that contains adaptive and innate immune cells that have tumor-promoting and anti-tumor effects. There is still much to learn about the diversity, plasticity, and functions of innate immune cells in the TIME and their roles in determining the response to immunotherapies. Experts discuss recent advances in our understanding of their biology in cancer as well as outstanding questions and potential therapeutic avenues.

A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells.

Tumor-infiltrating myeloid cells (TIMs) are key regulators in tumor progression, but the similarity and distinction of their fundamental properties across different tumors remain elusive. Here, by performing a pan-cancer analysis of single myeloid cells from 210 patients across 15 human cancer types, we identified distinct features of TIMs across cancer types. Mast cells in nasopharyngeal cancer were found to be associated with better prognosis and exhibited an anti-tumor phenotype with a high ratio of TNF+/VEGFA+ cells. Systematic comparison between cDC1- and cDC2-derived LAMP3+ cDCs revealed their differences in transcription factors and external stimulus. Additionally, pro-angiogenic tumor-associated macrophages (TAMs) were characterized with diverse markers across different cancer types, and the composition of TIMs appeared to be associated with certain features of somatic mutations and gene expressions. Our results provide a systematic view of the highly heterogeneous TIMs and suggest future avenues for rational, targeted immunotherapies.

An expanded landscape of human long noncoding RNA.

Long noncoding RNAs (lncRNAs) are emerging as key regulators of multiple essential biological processes involved in physiology and pathology. By analyzing the largest compendium of 14,166 samples from normal and tumor tissues, we significantly expand the landscape of human long noncoding RNA with a high-quality atlas: RefLnc (Reference catalog of LncRNA). Powered by comprehensive annotation across multiple sources, RefLnc helps to pinpoint 275 novel intergenic lncRNAs correlated with sex, age or race as well as 369 novel ones associated with patient survival, clinical stage, tumor metastasis or recurrence. Integrated in a user-friendly online portal, the expanded catalog of human lncRNAs provides a valuable resource for investigating lncRNA function in both human biology and cancer development.

Distinct epigenetic features of tumor-reactive CD8+ T cells in colorectal cancer patients revealed by genome-wide DNA methylation analysis.

BACKGROUND: Tumor-reactive CD8+ tumor-infiltrating lymphocytes (TILs) represent a subtype of T cells that can recognize and destroy tumor specifically. Understanding the regulatory mechanism of tumor-reactive CD8+ T cells has important therapeutic implications. Yet the DNA methylation status of this T cell subtype has not been elucidated. RESULTS: In this study, we segregate tumor-reactive and bystander CD8+ TILs, as well as naïve and effector memory CD8+ T cell subtypes as controls from colorectal cancer patients, to compare their transcriptome and methylome characteristics. Transcriptome profiling confirms previous conclusions that tumor-reactive TILs have an exhausted tissue-resident memory signature. Whole-genome methylation profiling identifies a distinct methylome pattern of tumor-reactive CD8+ T cells, with tumor-reactive markers CD39 and CD103 being specifically demethylated. In addition, dynamic changes are observed during the transition of naïve T cells into tumor-reactive CD8+ T cells. Transcription factor binding motif enrichment analysis identifies several immune-related transcription factors, including three exhaustion-related genes (NR4A1, BATF, and EGR2) and VDR, which potentially play an important regulatory role in tumor-reactive CD8+ T cells. CONCLUSION: Our study supports the involvement of DNA methylation in shaping tumor-reactive and bystander CD8+ TILs, and provides a valuable resource for the development of novel DNA methylation markers and future therapeutics.

CCGD-ESCC: A Comprehensive Database for Genetic Variants Associated with Esophageal Squamous Cell Carcinoma in Chinese Population.

Esophageal squamous-cell carcinoma (ESCC) is one of the most lethal malignancies in the world and occurs at particularly higher frequency in China. While several genome-wide association studies (GWAS) of germline variants and whole-genome or whole-exome sequencing studies of somatic mutations in ESCC have been published, there is no comprehensive database publically available for this cancer. Here, we developed the Chinese Cancer Genomic Database-Esophageal Squamous Cell Carcinoma (CCGD-ESCC) database, which contains the associations of 69,593 single nucleotide polymorphisms (SNPs) with ESCC risk in 2022 cases and 2039 controls, survival time of 1006 ESCC patients (survival GWAS) and gene expression (expression quantitative trait loci, eQTL) in 94 ESCC patients. Moreover, this database also provides the associations between 8833 somatic mutations and survival time in 675 ESCC patients. Our user-friendly database is a resource useful for biologists and oncologists not only in identifying the associations of genetic variants or somatic mutations with the development and progression of ESCC but also in studying the underlying mechanisms for tumorigenesis of the cancer. CCGD-ESCC is freely accessible at http://db.cbi.pku.edu.cn/ccgd/ESCCdb.

Transcatheter mitral valve implantation for degenerated mitral bioprostheses or failed surgical annuloplasty rings: A systematic review and meta-analysis.

BACKGROUND: Transcatheter mitral valve-in-valve (TMVIV) and valve-in-ring (TMVIR) implantation for degenerated mitral bioprostheses and failed annuloplasty rings have recently emerged as treatment options for patients deemed unsuitable for repeat surgery. METHODS: A systematic literature review was conducted to summarize the data regarding the baseline characteristics and clinical outcomes of patients undergoing TMVIV and TMVIR procedures. RESULTS: A total of 245 patients (172 patients who underwent TMVIV surgery and 73 patients who underwent TMVIR surgery) were included in the study; 93.5% of patients experienced successful TMVIV or TMVIR implantation. The mortality rates at discharge, 30 days, and 6 months were 5.7%, 8.1%, and 23.4%, respectively. The transapical (TA) access route was used in most procedures (55.2%). The TA and transseptal (TS) access routes resulted in similar outcomes. No significant differences were observed in the short-term outcomes between the patients who developed mitral stenosis versus mitral regurgitation as the mode of failure. CONCLUSIONS: TMVIV and TMVIR implantation for degenerated mitral bioprostheses and failed annuloplasty rings are safe and effective. Both procedures, via TA or TS access, can result in excellent short-term clinical outcomes in patients with mitral stenosis or regurgitation, but long-term follow-up data are currently lacking to determine the durability of these procedures.

Systematic identification and annotation of multiple-variant compound effects at transcription factor binding sites in human genome.

Understanding the functional effects of genetic variants is crucial in modern genomics and genetics. Transcription factor binding sites (TFBSs) are one of the most important cis-regulatory elements. While multiple tools have been developed to assess functional effects of genetic variants at TFBSs, they usually assume that each variant works in isolation and neglect the potential "interference" among multiple variants within the same TFBS. In this study, we presented COPE-TFBS (Context-Oriented Predictor for variant Effect on Transcription Factor Binding Site), a novel method that considers sequence context to accurately predict variant effects on TFBSs. We systematically re-analyzed the sequencing data from both the 1000 Genomes Project and the Genotype-Tissue Expression (GTEx) Project via COPE-TFBS, and identified numbers of novel TFBSs, transformed TFBSs and discordantly annotated TFBSs resulting from multiple variants, further highlighting the necessity of sequence context in accurately annotating genetic variants. COPE-TFBS is freely available for academic use at http://cope.cbi.pku.edu.cn/.

Percutaneous Endoscopic Lumbar Discectomy for L5S1 Lumbar Disc Herniation Using a Transforaminal Approach Versus an Interlaminar Approach: A Systematic Review and Meta-Analysis.

BACKGROUND: Several studies have compared the clinical efficacy of percutaneous endoscopic lumbar discectomy for L5-S1 lumbar disc herniation (LDH) using a transforaminal approach with an interlaminar approach, but with contradictory results. The aim of this study was to explore the comparison of efficacy and safety between percutaneous endoscopic transforaminal discectomy (PETD) and percutaneous endoscopic interlaminar discectomy (PEID) for L5-S1 LDH. METHODS: Six common databases were comprehensively searched, and relevant studies were included into the analysis when they met all the inclusion criteria. RESULTS: Nine studies involving 621 patients were included into the study. The results indicated that PETD was significantly associated with greater fluoroscopy times (mean difference [MD], 9.28 times; 95% confidence interval [CI], 6.84-11.71; P < 0.01) and longer operative time (MD, 16.51 minutes; 95% CI, 4.01-29.02; P = 0.01) compared with PEID. However, there were no distinct differences between PETD and PEID in estimated blood loss (P = 0.24), bed time after surgery (P = 0.32), hospitalization time (P = 0.27), or MacNab evaluation (P = 0.78). Similarly, no obvious differences were detected between PETD and PEID regarding Visual Analogue Scale score, Japanese Orthopedic Association (JOA) score, or Oswestry Disability Index (ODI) when measured preoperatively, 1 day postoperatively, 3 months postoperatively, or at the last follow up. In addition, no significant difference was found regarding overall incidence of complications between PETD and PEID (P = 0.14). Nevertheless, a significantly lower incidence rate of dural tear was observed in PETD compared with PEID (P = 0.04). CONCLUSIONS: PETD had comparable clinical efficacy and safety compared with PEID; however, PEID was superior to PETD regarding fluoroscopy times and operative time. Therefore, PEID might be a better surgical procedure for L5S1 LDH.

Prognostic and clinicopathological value of SIRT3 expression in various cancers: a systematic review and meta-analysis.

BACKGROUND: Several studies have explored the prognostic value of sirtuin 3 (SIRT3) in various cancers, but obtained inconsistent results. The current systematic review and meta-analysis was conducted to investigate the association between SIRT3 expression and prognosis in various cancers. METHODS: PubMed, Embase, Web of Science and the Cochrane Library were comprehensively retrieved by the end of September 29, 2017. All the relevant studies were checked and included in the meta-analysis if they met the inclusion criteria. RESULTS: A total of 17 studies involving 2,865 patients were included in the systematic review and meta-analysis. The results indicated that SIRT3 expression was not significantly associated with overall survival (OS) (hazard ratio [HR]=0.87, 95% CI=0.59-1.29, P=0.50) and disease-free survival (HR=0.87, 95% CI=0.57-1.31, P=0.50) in total various cancers. However, significant relationship between SIRT3 expression and OS in specific cancers was detected, including chronic lymphocytic leukemia (CLL) (HR=0.48, 95% CI=0.26-0.89, P=0.019), hepatocellular carcinoma (HCC) (HR=0.56, 95% CI=0.42-0.74, P<0.001), pancreatic carcinoma (PC) (HR=0.55, 95% CI=0.30-1.00, P=0.049), renal cell carcinoma (RCC) (HR=0.13, 95% CI=0.02-0.98, P=0.048), breast cancer (BC) (HR=2.53, 95% CI=1.83-3.67, P<0.001), colon cancer (CC) (HR=1.87, 95% CI=1.12-3.26, P=0.022) and non-small-cell lung cancer (NSCLC) (HR=2.20, 95% CI=1.38-3.50, P=0.001). Moreover, SIRT3 expression was obviously associated with tumor size (odds ratio [OR]=1.41, 95% CI=1.02-1.94, P=0.04), tumor differentiation (OR=1.52, 95% CI=1.08-2.16, P=0.02) and clinical stage (OR=2.07, 95% CI=1.23-3.46, P=0.01) in HCC. CONCLUSION: SIRT3 was distinctly related to the OS in specific cancers. SIRT3 was an unfavorable prognostic factor in BC, CC and NSCLC; however, it was also a favorable prognostic factor in CLL, HCC, PC and RCC, especially in HCC.

Prognostic value of platelet-to-lymphocyte ratio in pancreatic cancer: a comprehensive meta-analysis of 17 cohort studies.

BACKGROUND AND AIMS: Several studies were conducted to explore the prognostic value of platelet-to-lymphocyte ratio (PLR) in pancreatic cancer and have reported contradictory results. This study aims to summarize the prognostic role of PLR in pancreatic cancer. MATERIALS AND METHODS: Embase, PubMed and Cochrane Library were completely searched. The cohort studies focusing on the prognostic role of PLR in pancreatic cancer were eligible. The overall survival (OS) and progression-free survival (PFS) were analyzed. RESULTS: Fifteen papers containing 17 cohort studies with pancreatic cancer were identified. The results showed patients that with low PLR might have longer OS when compared to the patients with high PLR (hazard ratio=1.28, 95% CI=1.17-1.40, P<0.00001; I2=42%). Similar results were observed in the subgroup analyses of OS, which was based on the analysis model, ethnicity, sample size and cut-off value. Further analyses based on the adjusted potential confounders were conducted, including CA199, neutrophil-to-lymphocyte ratio, modified Glasgow Prognostic Score, albumin, C-reactive protein, Eastern Cooperative Oncology Group, stage, tumor size, nodal involvement, tumor differentiation, margin status, age and gender, which confirmed that low PLR was a protective factor in pancreatic cancer. In addition, low PLR was significantly associated with longer PFS when compared to high PLR in pancreatic cancer (hazard ratio=1.27, 95% CI=1.03-1.57, P=0.03; I2=33%). CONCLUSION: In conclusion, it was found that high PLR is an unfavorable predictor of OS and PFS in patients with pancreatic cancer, and PLR is a promising prognostic biomarker for pancreatic cancer.

The prognostic value of high LncRNA AFAP1-AS1 expression in various cancers: A systematic review and meta-analysis containing 21 studies.

BACKGROUNDS: Plenty of studies have been conducted to explore the prognostic value of LncRNA AFAP1-AS1 in various cancers, however, with contradictory outcomes. The aim of the current study was to explore the prognostic value of high LncRNA AFAP1-AS1 expression in various cancers. METHODS: PubMed, EMBASE, Web of Science, Cochrane library, China National Knowledge Internet (CNKI) and Wan-fang database were comprehensively retrieved, and all the relevant studies were included into the study. RESULTS: A total of 21 studies involving 2179 patients were finally included into the systematic review and meta-analysis. Compared to low LncRNA AFAP1-AS1 expression, high LncRNA AFAP1-AS1 expression was significantly related to shorter OS (HR = 2.02, 95%CI = 1.51-2.70, P < 0.001; I2 = 78%), DFS(HR = 1.80, 95%CI = 1.16-2.80, P = 0.009; I2 = 0%), RFS (HR = 2.90, 95%CI = 1.79-4.69, P < 0.001; I2 = 38%)and PFS(HR = 2.18, 95%CI = 1.62-2.92, P < 0.001; I2 = 0%) in patients with various cancers. Besides, high LncRNA AFAP1-AS1 expression was significantly associated with smoking (P < 0.001), advanced clinical stage (P < 0.001), larger tumor size (P < .001), earlier tumor metastasis (P < 0.001), earlier lymph nodal involvement (P = 0.002) and vascular invasion (P < 0.001) in various cancers. CONCLUSIONS: Cancer patients with high LncRNA AFAP1-AS1 expression had shorter OS, DFS, RFS and PFS compared to those with low expression. Moreover, high LncRNA AFAP1-AS1 expression was significantly related to advanced clinical stage, larger tumor size, earlier tumor metastasis, earlier lymph nodal involvement and vascular invasion. High LncRNA AFAP1-AS1 expression was an unfavorable prognostic factor in various cancers.

Prognostic role of the neutrophil-to-lymphocyte ratio in pancreatic cancer: A meta-analysis containing 8252 patients.

Several studies were carried out to explore the prognostic role of neutrophil-to-lymphocyte ratio (NLR) in pancreatic cancer, however, with contradictory results. The objectives of this study were to summarize the prognostic value of NLR in pancreatic cancer. Embase, PubMed and Cochrane Library were comprehensively retrieved. All the cohort studies focusing on the prognostic value of NLR in pancreatic cancer were eligible. 37 papers containing 43 cohort studies with pancreatic cancer were finally included into this study. The results presented that patients with low NLR might have longer OS when compared to the patients with high NLR (HR = 1.81, 95%CI = 1.59-2.05, P < 0.00001; I2 = 82%). Similar results were detected in the subgroup analyses of OS, which was based on the analysis model, ethnicity, treatment, sample size and cut-off value. In additions, low NLR was significantly associated with longer DFS when compared to high NLR in pancreatic cancer (HR = 1.66, 95%CI = 1.17-2.35, P = 0.005; I2 = 67%). Moreover, patients with low NLR had significantly smaller tumor size (P = 0.0007), better differentiation (P = 0.003), earlier stage (P = 0.02) and low CA-199 level (P = 0.007). In conclusion, it was revealed that low NLR was a favorable predictor of OS and DFS in patients with pancreatic cancer, and NLR is a promising prognostic biomarker for pancreatic cancer.

Prognostic role of podocalyxin-like protein expression in various cancers: A systematic review and meta-analysis.

Several studies were conducted to explore the prognostic significance of podocalyxin-like protein (PODXL) expression in various cancers, with contradictory. This study aims to summarize the prognostic significance of PODXL expression in cancers. PubMed, the Cochrane Library and Embase were completely retrieved. The prospective or retrospective studies focusing on the prognostic role of PODXL expression in cancers were eligible. The endpoints were overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS).12 studies involving a total of 5,309 patients were identified. The results indicated that high PODXL expression was significantly associated with worse OS when compared to the low PODXL expression (HR=1.76, 95%CI=1.53-2.04, p<0.00001; I2=41%, p=0.08). And similar results were detected in the subgroup analysis of analysis model, ethnicity, sample size, tumor type and antibody type. And the results also showed that high PODXL expression was obviously related to shorter DSS (HR=2.47, 95%CI=1.53-3.99, p=0.0002; I2=66%, p=0.03) and DFS (HR=2.12, 95%CI=1.58-2.85, p<0.00001; I2=19%, p=0.29). In conclusion, it was revealed that high PODXL expression is an unfavorable predictor of OS, DSS and DFS in patients with cancers, and high PODXL expression is a promising prognostic biomarker for cancers, especially for patients in European.

Neutrophil-to-Lymphocyte Ratio Is a Potential Prognostic Biomarker in Patients with Ovarian Cancer: A Meta-Analysis.

BACKGROUND AND AIMS: Plenty of studies were conducted to explore the prognostic significance of neutrophil-to-lymphocyte ratio (NLR) in ovarian cancer with contradictory results. This study aims to summarize the prognostic significance of NLR in patients with ovarian cancer. METHODS: A literature search in PubMed, Cochrane Library, and Embase was conducted. The endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: Eleven studies involving a total of 2,892 patients were identified. The results indicated that patients with high NLR had shorter PFS compared to patients with low NLR in ovarian cancer (HR = 1.55, 95% CI = 1.15-2.08, p = 0.004, and I2 = 61%). Similarly, high NLR was related to shorter OS (HR = 1.51, 95% CI = 1.03-2.23, p = 0.04, and I2 = 85%). Moreover, high NLR was significantly associated with shorter PFS when the NLR cut-off was less than 3.3 (p = 0.03) or when treatment is operation (p = 0.002). In addition, high NLR was distinctly related to worse OS in Asian people (p = 0.04) or operation (p = 0.04). CONCLUSION: High NLR was associated with shorter PFS and shorter OS in ovarian cancer. NLR is potentially a promising prognostic biomarker in patients with ovarian cancer.

Accurately annotate compound effects of genetic variants using a context-sensitive framework.

In genomics, effectively identifying the biological effects of genetic variants is crucial. Current methods handle each variant independently, assuming that each variant acts in a context-free manner. However, variants within the same gene may interfere with each other, producing combinational (compound) rather than individual effects. In this work, we introduce COPE, a gene-centric variant annotation tool that integrates the entire sequential context in evaluating the functional effects of intra-genic variants. Applying COPE to the 1000 Genomes dataset, we identified numerous cases of multiple-variant compound effects that frequently led to false-positive and false-negative loss-of-function calls by conventional variant-centric tools. Specifically, 64 disease-causing mutations were identified to be rescued in a specific genomic context, thus potentially contributing to the buffering effects for highly penetrant deleterious mutations. COPE is freely available for academic use at http://cope.cbi.pku.edu.cn.

Prognostic role of platelet to lymphocyte ratio in hepatocellular carcinoma: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Several studies were conducted to explore the prognostic significance of platelet to lymphocyte ratio (PLR) in hepatocellular carcinoma (HCC), however, contradictory results across most reports were documented. To this end, we present a systematic review that aims to summarize the prognostic significance of PLR in patients with HCC. RESULTS: A total of 10 studies involving a total of 2,315 patients were identified. The Newcastle-Ottawa Quality Assessment Scale (NOS) of each included study was greater than or equal to 5. The results indicated that high PLR was significantly associated with a worse OS when compared to the low PLR (HR = 1.60, 95% CI = 1.23-2.08, p = 0.0005; I2 = 88%, p < 0.00001). Similar results were detected in the subgroup analysis of the analysis model, cut-off value, ethnicity, sample size and therapy. However, no obvious correlation between the PLR and DFS/RFS in patients with HCC was observed (HR = 1.21, 95% CI = 0.87-1.67, p = 0.26; I2 = 61%, p = 0.07). MATERIALS AND METHODS: A complete literature search in the PubMed, Cochrane Library and Embase database was performed. Retrospective and prospective studies focusing on the role of PLR on the prognosis in HCC were all deemed as "suitable" for our scope. The endpoints determined were: the overall survival (OS), disease-free survival (DFS), recurrence-free survival (RFS) and the progress free survival (PFS). CONCLUSIONS: The study revealed that high PLR is an unfavorable predictor of OS in patients with HCC, and high PLR is a promising prognostic biomarker for HCC, especially for patients in Asia.

Comparative effectiveness of combined therapy inhibiting EGFR and VEGF pathways in patients with advanced non-small-cell lung cancer: a meta-analysis of 16 phase II/III randomized trials.

BACKGROUND & AIMS: Combined therapy inhibiting EGFR and VEGF pathways is becoming a promising therapy in the treatment of advanced non-small-cell lung cancer (NSCLC), however, with controversy. The study aims to compare the efficacy of combined inhibition therapy versus control therapy (including placebo, single EGFR inhibition and single VEGF inhibition) in patients with advanced NSCLC. MATERIALS AND METHODS: An adequate literature search in EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) was conducted. Phase II or III randomized controlled trials (RCTs) that compared effectiveness between combined inhibition therapy and control therapy in patients with advanced NSCLC were eligible. The endpoint was overall response rate (ORR), progression free survival (PFS) and overall survival (OS). RESULTS: Sixteen phase II or III RCTs involving a total of 7,109 patients were included. The results indicated that the combined inhibition therapy significantly increased the ORR (OR = 1.59, 95% CI = 1.36-1.87, p<0.00001; I2 = 36%) when compared to control therapy. In the subgroup analysis, the combined inhibition therapy clearly increased the ORR (OR = 2.04, 95% CI = 1.60-2.60, p<0.00001; I2 = 0%) and improved the PFS (HR = 0.78, 95% CI = 0.71-0.85, p<0.00001;I2 = 0%) when compared with the placebo, and similar results was detected when compared with the single EGFR inhibition in terms of ORR (OR = 1.39, 95% CI = 1.12-1.74, p = 0.003; I2 = 30%) and PFS (HR = 0.73, 95% CI = 0.67-0.81, p<0.0001; I2 = 50%). No obvious difference was found between the combined inhibition therapy and single VEGF inhibition in term of ORR, however, combined inhibition therapy significantly decreased the PFS when compared to the single VEGF inhibition therapy (HR = 1.70, 95% CI = 1.34-2.17, p<0.0001; I2 = 50%). Besides, no significant difference was observed between the combined inhibition therapy and control therapy in term of OS (including placebo, single EGFR inhibition and single VEGF inhibition) (HR = 0.98, 95% CI = 0.92-1.04, p = 0.41; I2 = 0%). CONCLUSIONS: Combined inhibition therapy was superior to placebo and single EGFR inhibition in terms of ORR, PFS for advanced NSCLC, however, no statistical difference were found in term of OS. Besides, combined inhibition therapy was not superior to single VEGF inhibition in terms of ORR, PFS and OS. Therefore, combined inhibition therapy is recommended to treat advanced NSCLC patients.