Construction of a TAN-associated risk score model with integrated multi-omics data analysis and clinical validation in gastric cancer.

AIMS: An increasing number of studies have highlighted the biological significance of neutrophil activation and polarization in tumor progression. However, the characterization of tumor-associated neutrophils (TANs) is inadequately investigated. MATERIALS AND METHODS: Patients' expression profiles were obtained from TCGA, GEO, and IMvigor210 databases. Six algorithms were used to assess immune cell infiltration. RNA sequencing was conducted to evaluate the differentially expressed genes between induced N1- and N2-like neutrophils. A TAN-associated risk score (TRS) model was established using a combination of weighted gene co-expression network analysis (WGCNA) and RNA-seq data and further assessed in pan-cancer. A clinical cohort of 117 GC patients was enrolled to assess the role of TANs in GC via immunohistochemistry (IHC). KEY FINDINGS: A TRS signature was built with 10 TAN-related genes (TRGs) and most TRGs were highly abundant in the TANs of the GC microenvironment. The TRS model could accurately predict patients' prognosis, as well as their responses to chemotherapy and immunotherapy. The TRS was positively correlated with pro-tumor immune cells and exhibited negative relationship with anti-tumor immune cells. Additional functional analyses revealed that the signature was positively related to pro-tumor and immunosuppression pathways, such as the hypoxia pathway, across pan-cancer. Furthermore, our clinical cohort demonstrated TANs as an independent prognostic factor for GC patients. SIGNIFICANCE: This study constructed and confirmed the value of a novel TRS model for prognostic prediction of GC and pan-cancer. Further evaluation of TRS and TANs will help strengthen the understanding of the tumor microenvironment and guide more effective therapeutic strategies.

Integrative analysis confirms TPX2 as a novel biomarker for clinical implication, tumor microenvironment, and immunotherapy response across human solid tumors.

Targeting Protein for Xenopus Kinesin Like Protein 2 (TPX2) serves as a microtubule associated protein for the regulation of spindle assembly and tumorigenesis. We aim to investigate the prognostic and immunological role of TPX2 in pan-cancer. TCGA database, Tumor Immune Single-cell Hub (TISCH), and Human Protein Atlas (HPA) were retrieved to evaluate the expression pattern of TPX2 as well as its diagnostic and prognostic value in solid tumors. Genomic alterations of TPX2 were assessed with cBioPortal database. In vitro experiments in lung adenocarcinoma (LUAD) were performed to confirm the potential role of TPX2. Overexpression of TPX2 was found in 22 types of cancers, and was positively related with copy number variations (CNV) and negative with methylation. Up-regulated TPX2 could predict worse outcomes in the majority of cancers. Single-cell analysis revealed that TPX2 was mainly distributed in malignant cells (especially in glioma) and proliferating T cells. Genomic alteration of TPX2 was common in different types of tumors, while with prognostic value in two types of cancers. Additionally, significant correlations were found between TPX2 expression and tumor microenvironment (including stromal cells and immune cells) as well as immune related genes across cancer types. Drug sensitivity analysis revealed that TPX2 could predict response to chemotherapy and immunotherapy. Functional analyses demonstrated close relationship of TPX2 with immune function and malignant phenotypes. Finally, it was confirmed that knockdown of TPX2 could reduce proliferation and migration ability of LUAD cells. In summary, TPX2 could serve as a diagnostic and prognostic biomarker and a potential immunotherapy marker.

Evaluation of retinal structural and functional changes after silicone oil removal in patients with rhegmatogenous retinal detachment: a retrospective study.

BACKGROUND: To evaluate retinal structural and functional changes after silicone oil (SO) removal in eyes with macula-off rhegmatogenous retinal detachment (RRD). METHODS: Best-corrected visual acuity (BCVA) testing, microperimetry, and optical coherence tomography angiography were performed in 48 eyes with macula-off RRD before and 3 months after SO removal. The values of healthy contralateral eyes were used as control data. Correlations between retinal vessel density (VD), retinal nerve fiber layer thickness (RNFLT), the interval between retinal detachment and surgery, the duration of SO tamponade, the follow-up time after SO removal, and visual function were analyzed. RESULTS: Significant increases in 2˚ fixation rate (FR), 4˚ FR, 2˚ mean retinal sensitivity (MRS), 6˚ MRS, parafoveal superficial capillary plexus VD and RNFLT were observed after SO removal (all P < 0.05). The increase of 2˚ MRS and 6˚ MRS were correlated with the duration of SO tamponade and the follow-up time after SO removal respectively (all P < 0.05). The last 2˚ MRS and 6˚ MRS were correlated with the duration of SO tamponade, the interval between retinal detachment and surgery, and the follow-up time after SO removal (all P < 0.01). The last FR in RRD eyes was close to that of contralateral eyes (P > 0.05). CONCLUSION: Retinal structure and function improved to different degrees after SO removal. Fixation stability and retinal sensitivity increased more than BCVA postoperatively. Retinal sensitivity, which was affected by the interval between retinal detachment and surgery and the duration of SO tamponade, gradually recovered after SO removal.

Metabolic reprogramming involves in transition of activated/resting CD4+ memory T cells and prognosis of gastric cancer.

Background: Little is known on how metabolic reprogramming potentially prompts transition of activated and resting CD4+ memory T cells infiltration in tumor microenvironment of gastric cancer (GC). The study aimed to evaluate their interactions and develop a risk model for predicting prognosis in GC. Methods: Expression profiles were obtained from TCGA and GEO databases. An immunotherapeutic IMvigor210 cohort was also enrolled. CIBERSORT algorithm was used to evaluate the infiltration of immune cells. The ssGSEA method was performed to assess levels of 114 metabolism pathways. Prognosis and correlation analysis were conducted to identify metabolism pathways and genes correlated with activated CD4+ memory T cells ratio (AR) and prognosis. An AR-related metabolism gene (ARMG) risk model was constructed and validated in different cohorts. Flow cytometry was applied to validate the effect of all-trans retinoic acid (ATRA) on CD4+ memory T cells. Results: Since significantly inverse prognostic value and negative correlation of resting and activated CD4+ memory T cells, high AR level was associated with favorable overall survival (OS) in GC. Meanwhile, 15 metabolism pathways including retinoic acid metabolism pathway were significantly correlated with AR and prognosis. The ARMG risk model could classify GC patients with different outcomes, treatment responses, genomic and immune landscape. The prognostic value of the model was also confirmed in the additional validation, immunotherapy and pan-cancer cohorts. Functional analyses revealed that the ARMG model was positively correlated with pro-tumorigenic pathways. In vitro experiments showed that ATRA could inhibit levels of activated CD4+ memory T cells and AR. Conclusion: Our study showed that metabolic reprogramming including retinoic acid metabolism could contribute to transition of activated and resting CD4+ memory T cells, and affect prognosis of GC patients. The ARMG risk model could serve as a new tool for GC patients by accurately predicting prognosis and response to treatment.

R-LESS-RP versus C-LESS-RP: a single-institution retrospective comparative study.

This study aimed to compare the peri- and postoperative outcomes of patients treated with conventional versus robot-assisted laparoendoscopic single-site radical prostatectomy (C-LESS-RP vs. R-LESS-RP). Data of patients with prostate cancer (106 who underwent C-LESS-RP, 124 underwent R-LESS-RP) were retrospectively collected and analyzed. All operations were performed by the same surgeon from January 8, 2018, to January 6, 2021, in the same institution. Information on clinical characteristics and perioperative outcomes was obtained from records at the medical institution. Postoperative outcomes were acquired from follow-up. Intergroup differences were retrospectively analyzed and compared. All patients had similar clinical characteristics in meaningful aspects. The perioperative outcomes were better with R-LESS-RP than with C-LESS-RP in terms of operation time (120 min vs. 150 min, p < 0.05), estimated blood loss (17.68 ml vs. 33.68 ml, p < 0.05), and analgesic duration (0 days vs. 1 days, p < 0.05). The drainage tube duration and postoperative stay did not differ significantly between groups. However, R-LESS-RP was more expensive than C-LESS-RP (56559.510 CNY vs. 44818.27 CNY, p < 0.05). The patients who underwent R-LESS-RP had better urinary incontinence recovery and higher European quality of life visual analog scale scores than those who underwent C-LESS-RP. However, no significant intergroup difference was noted in biochemical recurrence. In conclusion, R-LESS-RP could achieve better perioperative outcomes, especially for those skilled surgeons who have mastered C-LESS-RP. Additionally, R-LESS-RP accelerated the recovery from urinary incontinence effectively and presented some benefits in health-related quality of life with additional costs.

Clinical implication and immunological landscape analyses of ANLN in pan-cancer: A new target for cancer research.

BACKGROUND: Anillin is a F-actin binding protein (ANLN) mainly involved in the process of cytokinesis and known to be dysregulated in diverse cancers. However, the role of ANLN in pan-cancer prognosis and tumor immunity remains unclear. METHODS: Gene expression profiles of 31 solid tumors were downloaded from The Cancer Genome Atlas (TCGA) database. ANLN mRNA and protein expression were quantified using quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC). Protein expression of ANLN was further confirmed in Human Protein Atlas (HPA) database. Cox regression and Kaplan-Meier analysis were utilized to assess the prognostic value of ANLN in pan-cancer. The correlation between ANLN and different immune gene markers and infiltration cells was analyzed via ESTIMATE and CIBERSORT. A BLCA immunotherapy cohort: IMvigor (210) was used to confirm the role of ANLN in immune response. RESULTS: ANLN upregulation was detected in 21 types of cancers and was associated with poor overall survival (OS), disease-free interval (DFI), and progression-free interval (PFI) in most cancers except in THYM (Thymoma). Additionally, correlation analysis revealed a significantly positive association between ANLN expression and tumor mutation burden (TMB), microsatellite instability (MSI), immune cells infiltration. and immune checkpoint genes in various cancers. The BLCA immunotherapy cohort confirmed that patients with higher ANLN level had better immune responses and longer OS. CONCLUSION: ANLN may serve as a prognostic biomarker for pan-cancer. ANLN upregulation is associated with higher TMB, MSI, and immune cell infiltration in multiple types of tumors, shedding new light for cancer treatment.

Prognostic and Immunological Roles of Cell Cycle Regulator CDCA5 in Human Solid Tumors.

Background: There have been several studies evaluating the prognostic significance of cell division cycle associated 5 (CDCA5). However, few reports analyzed the correlation between CDCA5 and prognosis of diverse cancers based on large clinical data. We thus comprehensively analyzed CDCA5 expression and clinical significance using The Cancer Genome Atlas (TCGA) data from 31 types of solid tumors. Methods: The expression profiles of CDCA5 were investigated across pan-cancer samples from the TCGA. Cox regression and Kaplan-Meier analysis was performed to determine CDCA5's prognostic value. CDCA5 expression was further validated by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) in lung adenocarcinoma (LUAD). Results: We found that CDCA5 was significantly overexpressed in 22 types of tumors. Up-regulated CDCA5 was significantly related to poor survival in 13 types of tumors. Furthermore, CDCA5 expression was significantly associated with immune cell infiltration. Tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint expression were significantly correlated with CDCA5 expression. Additional analysis of IMvigor 210 cohort validated that patients with high level of CDCA5 had superior response to anti-PD-L1 therapy. Conclusion: Our findings suggested that CDCA5 could provide prognostic information in most types of cancers and contributed to tumor immune microenvironment.

Integrated Analyses of m6A Regulator-Based Signature on Its Clinical Application and Immunogenomic Landscape in Stomach Adenocarcinoma.

Background: The whole tumor microenvironment (TME) infiltration features monitored by integrated roles of different RNA N6-methyladenosine (m6A) regulators remain elusive. Our study is aimed at exploring the association between m6A modification patterns, TME cell-infiltrating levels, and patients' prognosis in stomach adenocarcinoma (STAD) patients. Methods: Consensus clustering was performed based on the integrated analyses of 17 m6A regulators and 229 m6A-related hallmark genes in STAD (The Cancer Genome Atlas (TCGA) cohort, n = 443; Gene Expression Omnibus (GEO) GSE57303, n = 70, GSE62254 n = 300, and GSE84437 n = 433). A m6ASig scoring system was calculated by the principal component analysis (PCA), and its prognostic value was validated in an independent dataset GES15459. Results: Three m6A clusters were identified among 1246 STAD patients, which had significant overall survival (OS) differences and demonstrated different TME immune cell infiltration and biological behaviors. According to the m6ASig score, which was generated from the m6A-related hallmark genes, STAD patients were divided into the high-m6ASig group (n = 585) and low-m6ASig group (n = 586). Patients in the high-m6ASig group had a notably prolonged OS and higher immune cell infiltration. Moreover, patients with higher m6ASig score were associated with higher microsatellite instability (MSI); higher PD-L1, CTLA4, and ERBB2 expressions; and greater tumor mutation burden (TMB). Patients with higher m6ASig score demonstrated a better immune response and drug sensitivity. Conclusion: Our m6ASig scoring system could characterize TME immune cell infiltration, thus predict patient's prognosis and immunotherapy and chemotherapy efficacy, offering a novel tool for the individualized therapeutic implications for STAD patients.

A novel 6-gene signature derived from tumor-infiltrating T cells and neutrophils predicts survival of bladder urothelial carcinoma.

Intratumoral immune cells were reported to be associated with prognosis of bladder urothelial carcinoma (BUC). However, the role of immune cells related genes in BUC prognosis is less well defined. In the study, we analyzed data retrieved from the Cancer Genome Atlas database and found higher neutrophils and lower T cells infiltration in BUC tumor tissues were significantly correlated with patients' worse prognosis. Additionally, the expression levels of 164 genes were significantly correlated with T cells and neutrophils proportions. A Cox proportional-hazards model integrating 6 genes expression (EMP1, RASGRP4, HSPA1L, AHNAK, SLC1A6, and PRSS8) was identified. The 6-gene signature outperformed other clinical factors in risk prediction and was an independent prognostic factor for BUC. The findings were further conformed in three Gene Expression Omnibus datasets (n=331) and Jiangsu Province Hospital cohort (n = 46). Gene set enrichment analysis revealed that the model was highly involved in some immune-related pathways. A comprehensive nomogram combining the model and other clinical parameters was finally constructed to facilitate clinical application. In conclusion, a T cell and neutrophil-associated 6-gene prognostic model was identified for the survival prediction of BUC patients.

Peripapillary changes after vitrectomy and silicone oil tamponade for rhegmatogenous retinal detachment.

PURPOSE: To evaluate the peripapillary changes after vitrectomy and silicone oil (SO) tamponade in eyes with rhegmatogenous retinal detachment (RRD). METHODS: In this study, 25-gauge vitrectomy with SO tamponade was performed in 22 eyes with RRD. The radial peripapillary capillary (RPC) vessel density (VD) and retinal nerve fiber layer thickness (RNFLT) were assessed by optical coherence tomography angiography at 2, 4, 8, and 12 weeks postoperatively. The values of healthy fellow eyes were used as controls. RESULTS: The global RPC VDs were significantly lower in the eyes with RRD than in fellow healthy eyes at 2 weeks (P < 0.001), and increased at 4 weeks, then decreased over time after surgery (F = 1.046, P = 0.377). The RPC VDs in the superior-hemifield were lower than those in the inferior-hemifield at 12 weeks postoperatively (t = -2.844, P = 0.010). The global RNFLTs decreased gradually after vitrectomy in the eyes with RRD (F = 1.312, P = 0.276). The RNFLTs in the superior-hemifield were thinner than those in the inferior-hemifield at 12 weeks postoperatively (t = -2.222, P = 0.037). The global, superior, and inferior RNFLTs were correlated with corresponding RPC VDs in the eyes with RRD at all time-points postoperatively (P < 0.05). CONCLUSION: RRD resulted in the decrease of RPC VDs. The RPC VDs recovered in the early postoperative period but were still lower than the normal level. Long-term application of SO tamponade resulted in the reduction of peripapillary VDs secondary to loss of RNFLTs.

Impact of the Stress Status of Employees on the Enterprise Technology Management Cost Through Matter-Element Analysis Under Psychological Health Education.

In this study, in order to analyze the stress sources and stress-coping strategies of employees in construction enterprises, to explore the influencing factors of enterprise technical management cost, and to offer suggestions for mental health education of employees, 372 employees of Shandong Construction Engineering Group Co., Ltd. were selected for a questionnaire survey. The influences of stress sources and stress-coping strategies on the mental health of employees were compared, based on different demographic variables. The evaluation model was constructed using the matter-element analysis to rank the factors influencing the enterprise technology management cost. The results showed that the stress value of work characteristics was the highest (4.26 ± 0.511), followed by the organizational structure and atmosphere (4.15 ± 0.382); stress-coping strategies at the individual level (1.84 ± 0.315) scored higher than that at the organizational level (1.67 ± 0.248) (P < 0.05). Notable differences were observed in balance between work and family between males and females (P < 0.05); in work characteristics, role orientation, personal relationship, and balance between work and family between subjects of different ages (P < 0.05); in work characteristics, and balance between work and family between the married and the unmarried (P < 0.05); and in role stress and work characteristics between subjects in different positions (P < 0.05). The evaluation results revealed that the factors influencing the technology management cost of enterprises included price index, development cost, fixed investment proportion, power equipment rate, mechanical artificial intelligence, labor cost, rate of technical equipment, the output value, informatization of technology management, and national policy. In conclusion, the two major sources of stress for employees in Luoyang Construction Engineering Group Co., Ltd. were as follows: (1) work characteristics and (2) organizational structure and atmosphere. Besides, many employees adopted the stress-coping strategies at the individual level, and enterprises needed to strengthen the psychological health education for employees at the organizational level. In practice, the enterprise needed to add importance to the development of mechanical artificial intelligence, informatization of technology management, and national policy.

Exosomal miR-10b-5p mediates cell communication of gastric cancer cells and fibroblasts and facilitates cell proliferation.

Tumor microenvironment interacts with gastric cancer (GC) cells and affects tumor development. The communication between GC cells and fibroblasts has not been clearly studied and understood. MiR-10b-5p was found highly expressed in tissue and serum samples of patients with advanced stages (stage III+IV) than that in early stage patients (stage I+II). The expression determination of serum exosomal microRNA was also shown with high expression of miR-10b-5p in GC patients with advanced stages. Dual-luciferase activity assays indicated that miR-10b-5p targeted PTEN in GC cells and KLF11 in fibroblasts. The silence of miR-10b-5p up-regulated the expression of PTEN and repressed PI3K/Akt/mTORC1 signaling in GC cells. Clonogenic assay and MTT assay demonstrated that miR-10b-5p inhibitor could significantly reduce the colony formation and cell viability of GC cells. And the incubation of exosomal miR-10b-5p could increase the proliferation of GC cells. Immunohistochemistry staining revealed that high expression of α-SMA was detected in GC tissues with advanced stages. The overexpression of miR-10b-5p down-regulated KLF11 expression and elevated TGFßR1 expression in fibroblasts. In addition, miR-10b-5p inhibitor blocked the secretion of TGFß1 in GC cells and the directional migration of fibroblasts. Therefore, up-regulated exosomal miR-10b-5p is involved in the interaction of GC cells and fibroblasts in tumor microenvironment via participating in the regulation of TGFß signaling pathway.

A panel of 13-miRNA signature as a potential biomarker for predicting survival in pancreatic cancer.

Some reports have evaluated the prognostic relevance of microRNAs (miRNAs) in patients with pancreatic cancer (PC). However, most studies focused on limited miRNAs with small number of patients. The aim of the study is to identify a panel of miRNA signature that could predict prognosis in PC with the data from The Cancer Genome Atlas (TCGA). A total of 167 PC patients with the corresponding clinical data were enrolled in our study. The miRNAs significantly associated with overall survival (OS) in PC patients were identified with Cox proportional regression model. A risk score formula was developed to evaluate the prognostic value of the miRNA signature in PC. Thirteen miRNAs were identified to be significantly related with OS in PC patients. Patients with high risk score suffered poor overall survival compared with patients who had low risk score. The multivariate Cox regression analyses showed that the miRNA signature could act as an independent prognostic indicator. In addition, the signature might serve as a predicator for treatment outcome. Our study identified a miRNA signature including 13 miRNAs which could serve as an independent marker in prognosis of PC.

Increased androgen levels in rats impair glucose-stimulated insulin secretion through disruption of pancreatic beta cell mitochondrial function.

Although insulin resistance is recognized to contribute to the reproductive and metabolic phenotypes of polycystic ovary syndrome (PCOS), pancreatic beta cell dysfunction plays an essential role in the progression from PCOS to the development of type 2 diabetes. However, the role of insulin secretory abnormalities in PCOS has received little attention. In addition, the precise changes in beta cells and the underlying mechanisms remain unclear. In this study, we therefore attempted to elucidate potential mechanisms involved in beta cell alterations in a rat model of PCOS. Glucose-induced insulin secretion was measured in islets isolated from DHT-treated and control rats. Oxygen consumption rate (OCR), ATP production, and mitochondrial copy number were assayed to evaluate mitochondrial function. Glucose-stimulated insulin secretion is significantly decreased in islets from DHT-treated rats. On the other hand, significant reductions are observed in the expression levels of several key genes involved in mitochondrial biogenesis and in mitochondrial OCR and ATP production in DHT-treated rat islets. Meanwhile, we found that androgens can directly impair beta cell function by inducing mitochondrial dysfunction in vitro in an androgen receptor dependent manner. For the first time, our study demonstrates that increased androgens in female rats can impair glucose-stimulated insulin secretion partly through disruption of pancreatic beta cell mitochondrial function. This work has significance for hyperandrogenic women with PCOS: excess activation of the androgen receptor by androgens may provoke beta cell dysfunction via mitochondrial dysfunction.

An ER-associated miRNA signature predicts prognosis in ER-positive breast cancer.

BACKGROUND: Breast cancer patients with positive estrogen receptor (ER) have a better prognosis. However, no prognostic miRNA signature was reported in the ER-positive breast cancer. The aim of the study was to identify and assess the prognostic significance of a miRNA signature in ER-positive breast cancer. METHODS: Two cohorts from The Cancer Genome Atlas (TCGA) dataset were used as training (n =596) and testing set (n =319). Differential expression profiling was identified in the training set. And the prognostic value of the miRNA signature was then assessed in the two cohorts. RESULTS: A total of 14 miRNAs were observed to be associated with the status of ER by significance analysis of microarrays (SAM) in the training set. Patients were characterized as high score or low score group according to the calculated risk scores from each miRNA. And patients in high score group had worse overall survival compared with those in low score group both in the training and testing set. CONCLUSIONS: Our study revealed a miRNA signature including 14 miRNAs associated with ER status which could act as a prognostic marker in ER-positive breast cancer.

The preoperative lymphocyte to monocyte ratio predicts clinical outcomes in patients with stage II/III gastric cancer.

Recently, lymphocyte to monocyte ratio (LMR) has been reported to be associated with clinical outcomes in some types of cancer but has not been explored in gastric cancer. In this study, we analyzed the association between LMR and clinical outcomes in stage II/III gastric cancer patients. Preoperative LMR calculated from peripheral lymphocyte and monocyte with corresponding clinical features from 426 stage II/III gastric cancer patients was noted. Kaplan-Meier method and Cox regression model were applied for overall survival (OS) and recurrence-free survival (RFS). Related with smaller tumor size (p<0.001), increased LMR could predict better OS [hazard ratio (HR), 0.688; 95% confidence interval (CI), 0.521-0.908, p=0.008] and was borderline significantly associated with better RFS (HR, 0.775; 95% CI, 0.592-1.01, p=0.06) in stage II/III gastric cancer patients through multivariable analysis. Subgroup analyses revealed that except stage III patients for RFS which yielded borderline significance (p=0.052), lower LMR was associated with poor clinical outcomes for patients regardless of different stages or whether the patients received adjuvant chemotherapy. The elevated preoperative LMR level was a significant favorable factor in the prognosis of stage II/III gastric cancer patients, especially for those with stage II. However, further validation of our findings is warranted.

Prognostic value of miR-21 in various cancers: an updating meta-analysis.

BACKGROUND: Recently, more and more studies investigated the value of microRNA (miRNA) as a diagnostic or prognostic biomarker in various cancers. MiR-21 was found dysregulated in almost all types of cancers. While the prognostic role of miR-21 in many cancers has been studied, the results were not consistent. METHODS: We performed a meta-analysis to investigate the correlation between miR-21 and survival of general cancers by calculating pooled hazard ratios (HR) and 95% confidence intervals (CI). RESULTS: The pooled results of 63 published studies showed that elevated miR-21 was a predictor for poor survival of general carcinomas, with pooled HR of 1.91 (95%CI: 1.66-2.19) for OS, 1.42 (95% CI: 1.16-1.74) for DFS and 2.2 (95% CI: 1.64-2.96) for RFS/CSS. MiR-21 was also a prognostic biomarker in the patients who received adjuvant therapy, with pooled HR of 2.4 (95%CI: 1.18-4.9) for OS. CONCLUSIONS: Our results showed that miR-21 could act as a significant biomarker in the prognosis of various cancers. Further studies are warranted before the application of the useful biomarker in the clinical.