Accumulating studies have focused on the clinicopathological and prognostic roles of large intergenic noncoding RNA regulator of reprogramming (lincRNA-ROR) in cancer patients. However, the results were controversial and unconvincing. Thus, we performed a meta-analysis to assess the associations between lincRNA-ROR expression and survival and clinicopathological characteristics of cancer patients.

We conducted this research to investigate the relationship between long intergenic non-protein coding RNA 673 (linc00673) expression and prognosis and clinicopathological parameters in human malignancies.

Butterfly glioblastoma (bGBM) is a rare brain tumor that invades both hemispheres by crossing the corpus callosum. bGBM is associated with a dismal prognosis with a median survival time of a few months. Surgical resection is a rare treatment option due to the unfavorable location and assumed poor risk-to-benefit ratio. Therefore, a biopsy-alone approach is considered the main treatment option. This meta-analysis aimed to systematically evaluate whether resection of bGBM is associated with improved overall survival compared with biopsy alone. We searched three databases to find studies that compare resection with biopsy in 6-, 12- and 18-months overall survival in patients with bGBM. We calculated the pooled relative risk (RR) of mortality using a random-effects model. Five studies with 194 patients were included in the meta-analysis. Mortality was decreased for resection compared with biopsy at 6-months (RR 0.63 [95% CI 0.44-0.91]). No significant differences in overall survival were found at 12 (RR 0.76 [95% CI 0.50-1.14]) and 18-months (RR 0.84 [95% CI 0.56-1.26]). Surgical resection of bGBM is associated with an improved 6-months overall survival compared with biopsy alone. We have not found strong evidence supporting the superiority of resection over biopsy alone in overall survival at 12 and 18-months.

To explore the expression profile and prognostic relevance of GLUT-1 in pancreatic cancer, a meta-analysis, bioinformatics analysis based on Gene Expression Omnibus (GEO), Oncomine dataset and The Cancer Genome Atlas (TCGA) database, and immunohistochemistry in tumor and normal tissue from 88 pancreatic ductal adenocarcinoma (PDAC) patients were performed. GLUT-1 was significantly overexpressed in pancreatic cancer but it could not be a significant biomarker for prognosis. TNM stage and pathological grade could be biomarker of poor prognosis of patients with pancreatic cancer.

Pancreatic neuroendocrine tumors (PanNETs) are a heterogeneous group of neoplasms with increasing incidence and unpredictable behavior. Whole-exome sequencing recently has shown very frequent somatic mutations in the alpha-thalassemia/mental retardation X-linked (ATRX) and death domain-associated protein (DAXX) genes in PanNETs. And the prognostic significance of altered ATRX/DAXX genes in PanNETs patients have been revealed in several reports. However, many of these include small sample size and hold controversial opinions. To increase statistical power, we performed a systematic review and meta-analysis to determine a pooled conclusion. We examined the impact of altered ATRX/DAXX genes mainly on overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) in PanNETs.

Breast cancer heterogeneity in histology and molecular subtype influences metabolic and proliferative activity and hence the acid load on cancer cells. We hypothesized that acid-base transporters and intracellular pH (pHi) dynamics contribute inter-individual variability in breast cancer aggressiveness and prognosis. We show that Na+,HCO3- cotransport and Na+/H+ exchange dominate cellular net acid extrusion in human breast carcinomas. Na+/H+ exchange elevates pHi preferentially in estrogen receptor-negative breast carcinomas, whereas Na+,HCO3- cotransport raises pHi more in invasive lobular than ductal breast carcinomas and in higher malignancy grade breast cancer. HER2-positive breast carcinomas have elevated protein expression of Na+/H+ exchanger NHE1/SLC9A1 and Na+,HCO3- cotransporter NBCn1/SLC4A7. Increased dependency on Na+,HCO3- cotransport associates with severe breast cancer: enlarged CO2/HCO3--dependent rises in pHi predict accelerated cell proliferation, whereas enhanced CO2/HCO3--dependent net acid extrusion, elevated NBCn1 protein expression, and reduced NHE1 protein expression predict lymph node metastasis. Accordingly, we observe reduced survival for patients suffering from luminal A or basal-like/triple-negative breast cancer with high SLC4A7 and/or low SLC9A1 mRNA expression. We conclude that the molecular mechanisms of acid-base regulation depend on clinicopathological characteristics of breast cancer patients. NBCn1 expression and dependency on Na+,HCO3- cotransport for pHi regulation, measured in biopsies of human primary breast carcinomas, independently predict proliferative activity, lymph node metastasis, and patient survival.

We conducted a comprehensive analysis to explore whether multiple interleukin (IL), IL-1β, IL-4, IL-6, IL-8 and IL-10, polymorphisms and IL proteins (IL-6, IL-10) relate to lung cancer (LC) susceptibility or clinical characteristics.

Epithelial to mesenchymal transition (EMT) is a highly conserved cellular process in several species, from worms to humans. EMT plays a fundamental role in early embryogenesis, wound healing, and cancer metastasis. For neural crest cell (NCC) development, EMT typically results in forming a migratory and potent cell population that generates a wide variety of cell and tissue, including cartilage, bone, connective tissue, endocrine cells, neurons, and glia amongst many others. The degree of conservation between the signaling pathways that regulate EMT during development and metastatic cancer (MC) has not been fully established, despite ample studies. This systematic review and meta-analysis dissects the major signaling pathways involved in EMT of NCC development and MC to unravel the similarities and differences. While the FGF, TGFβ/BMP, SHH, and NOTCH pathways have been rigorously investigated in both systems, the EGF, IGF, HIPPO, Factor Receptor Superfamily, and their intracellular signaling cascades need to be the focus of future NCC studies. In general, meta-analyses of the associated signaling pathways show a significant number of overlapping genes (particularly ligands, transcription regulators, and targeted cadherins) involved in each signaling pathway of both systems without stratification by body segments and cancer type. Lack of stratification makes it difficult to meaningfully evaluate the intracellular downstream effectors of each signaling pathway. Finally, pediatric neuroblastoma and melanoma are NCC-derived malignancies, which emphasize the importance of uncovering the EMT events that convert NCC into treatment-resistant malignant cells.

Various studies investigating the clinical significance of FBXW7 mutation and/or expression have yielded inconclusive results in colorectal cancer (CRC) patients. Therefore, the present meta-analysis summarizes previous evidence and evaluates the clinical significance, including the prognostic role, of FBXW7 status in CRCs.

Colorectal cancer (CRC) is reported to be associated with some gene polymorphisms. However, the effect of the fat mass and obesity associated (FTO) gene on colorectal cancer is not yet clear. This meta-analysis aimed to investigate the association of the FTO gene polymorphism and colorectal cancer.

Several studies have highlighted the diagnostic potential of salivary microRNA (miRNA) in head and neck squamous cell cancer (HNSCC). The purpose of this meta-analysis was to summarize published studies and evaluate the diagnostic accuracy of salivary miRNA in HNSCC detection. In this meta-analysis, we systematically searched PubMed, EMBASE, and Cochrane Library databases for studies on miRNA and HNSCC diagnosis. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) with a summary receiver-operating characteristic curve were calculated using a bivariate random-effect meta-analysis model. Furthermore, subgroup analyses were conducted to explore the main sources of heterogeneity. Seventeen studies from ten articles, including 23 miRNA and a total of 759 subjects, were included in this meta-analysis. The pooled sensitivity and specificity of salivary miRNA in the diagnosis of HNSCC were 0.697 (95% CI: 0.644-0.744) and 0.868 (95% CI: 0.811-0.910), respectively. The overall area under the curve was 0.803 with a DOR of 12.915 (95% CI: 9.512-17.534). Salivary miRNAs are a promising non-invasive diagnostic biomarker with moderate accuracy for HNSCC. These results must be verified by large-scale prospective studies.

To analyze the prevalence of homologous recombination deficiency (HRD) in patients with pancreatic ductal adenocarcinoma (PDAC).

Objective: Associations between gene mutations and metastasis in gastric cancer (GC) remain contradictory, resulting in the inaccurate estimation of the magnitude of the risk associated with specific genotypes.Methods: In this study, we first screened out four key driver genes (TP53, PIK3CA, APC and ARID1A) by jointly analyzing the mutation levels and searching the literature for genes associated with GC metastasis. We then performed a meta-analysis to demonstrate the relationship between these key driver gene mutations and GC metastasis, including lymphatic and distance metastasis.Results: We found out four key driver genes (TP53, PIK3CA, APC and ARID1A), associated with risk of GC metastasis. The results showed that TP53 (OR 1.39, 95% CI 1.12-1.72) and APC mutations (OR 0.58, 95% CI 0.38-0.89) were associated with lymph node metastasis and distant metastasis in GC. And TP53 mutations (OR 1.65, 95% CI 1.25-2.18) were significantly related to GC metastasis in the Asian population. APC mutations (OR 0.54, 95% CI 0.29-1.00) were also related to GC metastasis in the European and American populations. There was no significant association with GC metastasis in PIK3CA or ARID1A mutations.Expert opinion:Mutations of TP53 and APC play important roles in lymph node metastasis and distant metastasis of GC and may be potential important biomarkers of progression and therapeutic targets. These observations should be further prospectively verified.

Objective: Several systematic reviews (SRs) have assessed the diagnostic accuracy of microRNAs (miRNAs) for NSCLC, and this overview aimed to assess the relationship between diagnostic accuracy of miRNAs for NSCLC and number of microRNAs combinations. Methods: Embase.com, PubMed, the Cochrane Library, and Web of Science were searched. The PRISMA-DTA was used for reporting quality evaluation. Meta-analysis was conducted to assess the pooled diagnostic accuracy of different miRNAs combinations, and subgroup analyses were performed based on the source of miRNA. Results: Fourteen SRs with 91 original studies were included. Three SRs had minimal reporting flaws, and 11 SRs had medium flaws. The pooled sensitivity and specificity were 0.76 and 0.80 for single miRNA, 0.80 and 0.81 for two miRNAs combined, 0.82 and 0.88 for three miRNAs combined, 0.88 and 0.92 for four miRNAs combined, 0.87 and 0.87 for five miRNAs combined, and 0.87 and 0.89 for six or more miRNAs combined. And miR-21 was mostly appeared. Subgroup analyses suggested that the serum-derived miRNA had the relatively best diagnostic value compared to other sources. Conclusions: Future studies should explore specific and serum-derived miRNAs in NSCLC and combine them to improve the diagnosis accuracy of NSCLC, which had great significance in economic efficiency.

Thirty-five previous meta-analyses have been reported on the individual glutathione S-transferase M1 (GSTM1) present/null, glutathione S-transferase T1 (GSTT1) present/null, and glutathione S-transferase P1 (GSTP1) IIe105Val polymorphisms with lung cancer (LC) risk. However, they did not appraise the credibility and explore the combined effects between the 3 genes and LC risk.We performed a meta-analysis and re-analysis of systematic previous meta-analyses to solve the above problems.Meta-analyses of Observational Studies in Epidemiology guidelines were used. Moreover, we employed false-positive report probability (FPRP), Bayesian false discovery probability (BFDP), and the Venice criteria to verify the credibility of current and previous meta-analyses.Significantly increased LC risk was considered as "highly credible" or "positive" for GSTM1 null genotype in Japanese (odds ratio (OR) = 1.30, 95% confidence interval (CI) = 1.17-1.44, I2 = 0.0%, statistical power = 0.997, FPRP = 0.008, BFDP = 0.037, and Venice criteria: AAB), for GSTT1 null genotype in Asians (OR = 1.23, 95% CI = 1.12-1.36, I2 = 49.1%, statistical power = 1.000, FPRP = 0.051, BFDP = 0.771, and Venice criteria: ABB), especially Chinese populations (OR = 1.31, 95% CI = 1.16-1.49, I2 = 48.9%, Statistical power = 0.980, FPRP = 0.039, BFDP = 0.673, and Venice criteria: ABB), and for GSTP1 IIe105Val polymorphism in Asians (Val vs IIe: OR = 1.28, 95% CI = 1.17-1.42, I2 = 30.3%, statistical power = 0.999, FPRP = 0.003, BFDP = 0.183, and Venice criteria: ABB). Significantly increased lung adenocarcinoma (AC) risk was also considered as "highly credible" or "positive" in Asians for the GSTM1 (OR = 1.35, 95% CI = 1.22-1.48, I2 = 25.5%, statistical power = 0.988, FPRP < 0.001, BFDP < 0.001, and Venice criteria: ABB) and GSTT1 (OR = 1.36, 95% CI = 1.17-1.58, I2 = 30.2%, statistical power = 0.900, FPRP = 0.061, BFDP = 0.727, and Venice criteria: ABB) null genotype.This study indicates that GSTM1 null genotype is associated with increased LC risk in Japanese and lung AC risk in Asians; GSTT1 null genotype is associated with increased LC risk in Chinese, and GSTP1 IIe105Val polymorphism is associated with increased LC risk in Asians.

Prostate adenocarcinoma, with its rising numbers and high fatality rate, is a daunting healthcare challenge to clinicians and researchers alike. The mainstay of our meta-analysis was to decipher differentially expressed genes (DEGs), their corresponding transcription factors (TFs), miRNAs (microRNA) and interacting pathways underlying the progression of prostate cancer (PCa). We have chosen multiple datasets from primary, castration-resistant, chemo-resistant and metastatic prostate cancer stages for investigation. From our tissue-specific and disease-specific co-expression networks, fifteen hub genes such as ACTB, ACTN1, CDH1, CDKN1A, DDX21, ELF3, FLNA, FLNC, IKZF1, ILK, KRT13, KRT18, KRT19, SVIL and TRIM29 were identified and validated by molecular complex detection analysis as well as survival analysis. In our attempt to highlight hub gene-associated mutations and drug interactions, FLNC was found to be most commonly mutated and CDKN1A gene was found to have highest druggability. Moreover, from DAVID and gene set enrichment analysis, the focal adhesion and oestrogen signalling pathways were found enriched which indicates the involvement of hub genes in tumour invasiveness and metastasis. Finally by Enrichr tool and miRNet, we identified transcriptional factors SNAI2, TP63, CEBPB and KLF11 and microRNAs, namely hsa-mir-1-3p, hsa-mir-145-5p, hsa-mir-124-3p and hsa-mir-218-5p significantly controlling the hub gene expressions. In a nutshell, our report will help to gain a deeper insight into complex molecular intricacies and thereby unveil the probable biomarkers and therapeutic targets involved with PCa progression.

Hematopoietic stem cell transplantation (HSCT) is the current mainstay treatment for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). However, tyrosine kinase inhibitors (TKI) also play a significant role in the treatment of these patients. We conducted this systematic review and meta-analysis to compare the efficacy of allogeneic (allo-) HSCT, autologous (auto-) HSCT, and chemotherapy (CMT) alone-all in combination with TKIs in adult Ph+ ALL patients.

Abnormal telomerase activity plays a key role in the development of carcinogenesis. The variants rs2736100 and rs2736098 of the telomerase reverse transcriptase (TERT) gene, which encodes the telomerase catalytic subunit, are associated with the risk of different types of cancers. However, the results remain controversy. We conducted a meta-analysis to more precisely assess this association. We comprehensively searched the PubMed and Web of Science databases up to June 1, 2020, and retrieved a total of 103 studies in 82 articles, including 89,320 cases and 121,654 controls. Among these studies, 69 published studies including 75,274 cases and 10,3248 controls were focused on rs2736100, and 34 published studies including 14,046 cases and 18,362 controls were focused on rs2736098. The results showed a strong association between variant rs2736100 and cancer risk in all populations. (G vs. T: OR 1.18, 95% CI 1.12-1.24; TG+GG vs. TT: OR 1.23, 95% CI 1.15-1.31; GG vs. TG+TT: OR 1.25, 95% CI 1.16-1.36); the variant rs2736098 was associated with cancer risk in all populations as well (A vs. G: OR 1.13, 95% CI 1.05-1.22; GA+AA vs. GG: OR 1.15, 95% CI 1.04-1.27; AA vs. GA+GG: OR 1.22, 95% CI 1.10-1.38). Stratified analysis based on the cancer type indicated that rs2736100 was associated with an increased risk of thyroid cancer, bladder cancer, lung cancer, glioma, and myeloproliferative neoplasms. rs2736098 only increased the risk of bladder cancer and lung cancer. Moreover, the TERT variants rs2736100 and rs2736098 were associated with a decreased risk of breast cancer and colorectal cancer. The variants rs2736098 and rs2736100 located in 5p15.33 around TERT were associated with increased cancer risk in all populations. These two variants had bidirectional effects in different tumors.

This study was conducted to evaluate the predictive efficacy of tumor mutation burden (TMB) in patients with non-small-cell lung cancer (NSCLC) receiving PD-1 antibodies. Embase, PubMed, Ovid Medline, and the Cochrane Library were systematically searched until May 24, 2020. The keywords included "PD-1," "TMB," and "NSCLC." Overall survival (OS) and progression-free survival (PFS) were summarized and combined using the hazard ratio (HR) and 95% confidence interval. Twenty-one studies with 9883 patients were included in the meta-analysis. The overall relapse rate ranged from 39.3% to 64.3% in the higher TMB group as compared with 0% to 40% in the lower TMB group. The median OS ranged from 2.9 to 23 mo in the higher TMB group as compared with 4.3 to 16.2 mo in the lower TMB group. Patients with a higher TMB had a better OS as compared with patients with a lower TMB (HR = 0.61, P < 0.001). Similarly, a higher TMB was also a good predictor of PFS in patients treated with PD1/PDL1 antibodies (HR = 0.55, P < 0.001). Our results suggest that among NSCLC patients receiving PD1/PDL1 antibodies, patients with higher TMB could have a better survival outcome.

Gastric cancer is a leading cause of cancer-related deaths with considerable heterogeneity among patients. Appropriate classifications are essential for prognosis prediction and individualized treatment. Although immunotherapy showed potential efficacy in a portion of patients with gastric cancer, few studies have tried to classify gastric cancer specifically based on immune signatures. In this study, we established a 3-subtype cluster with low (CLIM), medium (CMIM), and high (CHIM) enrichment of immune signatures based on immunogenomic profiling. We validated the classification in multiple independent datasets. The CHIM subtype exhibited a relatively better prognosis and showed features of "hot tumors", including low tumor purity, high stromal components, overexpression of immune checkpoint molecules, and enriched tumor-infiltrated immune cells (activated T cells and macrophages). In addition, CHIM tumors were also characterized by frequent ARID1A mutation, rare TP53 mutation, hypermethylation status, and altered protein expression (HER2, β-catenin, Cyclin E1, PREX1, LCK, PD-L1, Transglutaminase, and cleaved Caspase 7). By Gene Set Variation Analysis, "TGFβ signaling pathway" and "GAP junction" were enriched in CLIM tumors and inversely correlated with CD8+ and CD4+ T cell infiltration. Of note, the CHIM patients showed a higher response rate to immunotherapy (44.4% vs. 11.1% and 16.7%) and a more prolonged progression-free survival (4.83 vs. 1.86 and 2.75 months) than CMIM and CLIM patients in a microsatellite-independent manner. In conclusion, the new immune signature-based subtypes have potential therapeutic and prognostic implications for gastric cancer management, especially immunotherapy.