Prognostic and clinicopathological significance of GPRC5A in various cancers: A systematic review and meta-analysis

Background GPRC5A is associated with various cancer initiation and progression. Controversial findings have been reported about GPRC5A prognostic characteristics, and no meta-analysis has been conducted to assess the relationship between GPRC5A and cancer prognosis. Therefore, the objective of this meta-analysis is to evaluate the overall prognostic effectiveness of GPRC5A. Methods We first conducted a systematic search in the PubMed, Embase, Web of Science, CNKI, Cochrane, and WangFang databases. The hazard ratio (HR) and odds ratios (OR) with 95% CI were then pooled to assess the associations between GPRC5A expression and overall survival (OS), disease-free survival (DFS), event-free survival (EFS), and clinicopathological characteristics. Chi-squared test and I2 statistics were completed to evaluate the heterogeneity in our study. A random‐effects model was used when significant heterogeneity existed (I2>50% and p<0.05); otherwise, we chose the fixed-effect model. Subgroup analysis was stratified by tumor type, region, HR obtained measurements, and sample capacity to explore the source of heterogeneity. Results In total, 15 studies with 624 patients met inclusion criteria of this study. Our results showed that higher expression of GPRC5A is associated with worse OS (HR:1.69 95%CI: 1.20–2.38 I2 = 75.6% p = 0.000), as well as worse EFS (HR:1.45 95%CI: 1.02–1.95 I2 = 0.0% p = 0.354). Subgroup analysis indicated that tumor type might be the source of high heterogeneity. Additionally, cancer patients with enhanced GPRC5A expression were more likely to lymph node metastasis (OR:1.95, 95%CI 1.33–2.86, I2 = 43.9%, p = 0.129) and advanced tumor stage (OR: 1.83, 95%CI 1.15–2.92, I2 = 61.3%, p = 0.035), but not associated with age, sex, differentiation, and distant metastasis. Conclusion GPRC5A can be a promising candidate for predicting medical outcomes and used for accurate diagnosis, prognosis prediction for patients with cancer; however, the predictive value of GPRC5A varies significantly according to cancer type. Further studies for this mechanism will be necessary to reveal novel insights into application of GPRC5A in cancers.

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Correlation between miR-200 Family Overexpression and Cancer Prognosis

Disease Markers ◽

10.1155/2018/6071826 ◽

2018 ◽

Vol 2018 ◽

pp. 1-16 ◽

Cited By ~ 2

Author(s):

Wen Liu ◽

Kaiping Zhang ◽

Pengfei Wei ◽

Yue Hu ◽

Yaqin Peng ◽

...

Keyword(s):

Meta Analysis ◽

Disease Free Survival ◽

Progression Free Survival ◽

Convincing Evidence ◽

Test Method ◽

Cancer Prognosis ◽

Cochrane Library ◽

Cancer Type ◽

China National Knowledge Infrastructure ◽

Free Survival

The correlation between miR-200 family overexpression and cancer prognosis remains controversial. Therefore, we conducted a systematic review and meta-analysis by searching PubMed, Embase, Cochrane Library, China Biology Medicine disc (CBM), and China National Knowledge Infrastructure (CNKI) to identify eligible studies. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to evaluate the strength of the correlations. Additionally, different subgroup analyses and publication bias test were performed. Eventually, we analyzed 23 articles that included five tumor types and 3038 patients. Consequently, high expression of miR-200 family in various tumors was associated with unfavorable overall survival (OS) in both univariate (HR=1.32, 95% CI: 1.14–1.54, P<0.001) and multivariate (HR=1.32, 95% CI: 1.16–1.49, P<0.001) analyses. Likewise, a similar result was found in different subgroups of the patient source, cancer type, test method, sample source, miR-200 component, and sample size. However, no association of miR-200 family was detected with recurrence- or relapse-free survival (RFS) (univariate: HR=1.02, 95% CI: 0.96–1.09, P=0.47; multivariate: HR=1.07, 95% CI: 1.00–1.14, P=0.07), progression-free survival (PFS) (univariate: HR=0.96, 95% CI: 0.54–1.70, P=0.88; multivariate: HR=1.17, 95% CI: 0.86–1.61, P=0.32), and disease-free survival (DFS) (univariate: HR=0.90, 95% CI: 0.74–1.09, P=0.29; multivariate: HR=0.98, 95% CI: 0.68–1.41, P=0.90). Our findings have provided convincing evidence that miR-200 family overexpression suggested poor prognosis of various cancer types, which efforts may raise the potential use of miR-200 family for cancer prognosis in clinical practice.

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Prognostic Impact of Monocyte to Lymphocyte Ratio in Clinical Outcome for Patients with Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Galen Medical Journal ◽

10.31661/gmj.v9i0.1948 ◽

2020 ◽

Vol 9 ◽

pp. 1948

Author(s):

Masoud Nouri-Vaskeh ◽

Mohammad Mirza-Aghazadeh-Attari ◽

Fariba Pashazadeh ◽

Saber Azami-Aghdash ◽

Hadi Alizadeh ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Subgroup Analysis ◽

Meta Analysis ◽

Prognostic Significance ◽

Surrogate Marker ◽

Disease Free Survival ◽

Systemic Review ◽

Significant Heterogeneity ◽

Prognostic Impact ◽

Free Survival

Background: Lymphocyte to monocyte ratio (LMR) is a surrogate marker of systemic inflammation which is shown to be related to patient’s survival in multiple malignancies. An important implication of this marker potentially is neoplasms in which there is no correlation between prognosis and histopathological staging, or has no reliable chemical markers associated with prognosis. Herein, this meta-analysis aimed to investigate the prognostic role of LMR in the patients with hepatocellular carcinoma (HCC).Methods: In the current systemic review and meta-analysis, we conducted a systemic search of databases and indexing sources, including Medline (PubMed), EMBASE, Cochrane, Scopus, and ProQuest up to May 2019. We include studies evaluating the prognostic significance of LMR on patients with HCC. Overall survival (OS), disease free survival (DFS) and recurrence free survival (RFS) values were extracted from the studies and analyzed. The pooled hazard ratio with 95% confidence interval explored to identify the prognostic value of LMR in survival of the patients with HCC.Results: A total of 12 studies with a total sample size of 3750 were included. There was significant heterogeneity among the studies, so subgroup analysis was also performed. Overall analysis regarding OS showed an insignificant relationship between LMR and patient’s prognosis, subgroup based on LMR cut-offs did not yield any significant result, subgroup analysis for RFS founded statistically significant results and LMR was significantly related to DFS.Conclusion: High LMR was associated with increased DFS and RFS, in return this correlation was not observed for OS.

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Prognostic Value of MicroRNA-497 in Various Cancers: A Systematic Review and Meta-Analysis

Disease Markers ◽

10.1155/2019/2491291 ◽

2019 ◽

Vol 2019 ◽

pp. 1-9 ◽

Cited By ~ 2

Author(s):

Zhiqiang Liu ◽

Shanshan Wu ◽

Lei Wang ◽

Shuling Kang ◽

Bixing Zhao ◽

...

Keyword(s):

Overall Survival ◽

Prognostic Biomarker ◽

Data Extraction ◽

Meta Analysis ◽

Disease Free Survival ◽

Cancer Prognosis ◽

Cancer Type ◽

Free Survival ◽

Knowledge Infrastructure ◽

Hazard Ratios

Background. Some studies showed that microRNA-497 (miR-497) might act as a prognostic biomarker of cancer. However, the conclusion was not consistent. The aim of this study was to investigate the prognostic role of miR-497 in various carcinomas. Methods. We systematically searched the databases of PubMed, Embase, Web of Science, Chinese National Knowledge Infrastructure (CNKI), and Wanfang Data to identify relevant studies. Two independent reviewers performed the data extraction and assessed the study quality. Hazard ratios (HRs) with corresponding 95% confidence intervals (CIs) for overall survival (OS) and disease-free survival/relapse-free survival (DFS/RFS) were used to assess the associations between miR-497 expression and cancer prognosis. Results. A total of 15 studies involving 1760 participants fulfilled the inclusion criteria. The lower level of miR-497 expression was significantly associated with shorter overall survival (HR=2.19, 95% CI: 1.84-2.60). No significant association was found between miR-497 expression and DFS/RFS in various carcinomas (HR=1.17, 95% CI: 0.53-2.57). Subgroup analyses by ethnicity and cancer type showed the consistent results. Conclusion. Our studies suggested that miR-497 might be a prognostic biomarker in cancers. However, further multicenter prospective clinical researches are needed to confirm the association between miR-497 expression and cancer prognosis.

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Prognostic Value of Long Noncoding RNA NORAD in Various cancers: a meta-analysis

10.1101/2020.07.09.20150185 ◽

2020 ◽

Author(s):

Qin Yang ◽

Zheng Zhang ◽

Yuan-Yuan Gong ◽

Zhi-Ran Li ◽

Hua-Zhu Zhang ◽

...

Keyword(s):

Risk Factor ◽

Long Noncoding Rna ◽

Noncoding Rna ◽

Bioinformatics Analysis ◽

Meta Analysis ◽

Disease Free Survival ◽

Cancer Prognosis ◽

Clinicopathological Parameters ◽

Survival Outcomes ◽

Free Survival

Abstract Objective: Accumulating studies reported that noncoding RNA activated by DNA damage (NORAD) was correlated with poor survival outcomes for patients in different cancers. However, the effects of NORAD on cancer prognosis were controversial. Therefore, a meta-analysis was carried out to elucidate this issue. Methods: Literature search was performed to collect eligible relevant publications until June 2020. The pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association of NORAD with prognosis and clinical features in diverse cancers. In addition, bioinformatics analysis was also utilized to validate the results of the meta-analysis. Results: Fourteen relevant articles involving 867 patients were enrolled in the present study. The pooled results showed that elevated expression of NORAD was a risk factor for overall survival (HR = 1.46, 95% CI: 1.06-2.01, P = 0.020), disease-free survival (HR = 1.74, 95% CI: 1.18-2.57, P = 0.005) and recurrence-free survival. Besides, overexpression of NORAD significantly correlated with lymph node metastasis and T stage. Additionally, bioinformatics analysis further strengthened and complemented the results of the present study. Conclusion: Our results showed that NORAD was a risk factor for survival outcomes and clinicopathological parameters in cancer patients. These findings indicated that NORAD may be a promising candidate for prognosis prediction and potential therapeutic target in diverse cancers. Key words: Long noncoding RNA, NORAD, prognosis, cancer, meta-analysis

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The prognostic relevance of 14-3-3 expression in cancers: a meta-analysis

Journal of the Pakistan Medical Association ◽

10.47391/jpma.03-402 ◽

2021 ◽

pp. 1-9

Author(s):

Caihong Li ◽

Honglan Zhu ◽

Changlu Liu ◽

Ya Liu ◽

Ting Huang ◽

...

Keyword(s):

Cancer Patients ◽

Meta Analysis ◽

Disease Free Survival ◽

Size Analysis ◽

Tumor Type ◽

Cancer Specific Survival ◽

Free Survival ◽

Hazard Ratios ◽

Prognostic Importance ◽

Patient Prognosis

AbstractObjective: A number of recent clinical studies have identified a relationship between elevated expressions of 14-3-3 and poorer patient prognosis in the context of several cancers. The present meta-analysis was therefore conducted to gain an enhanced understanding of the prognostic importance of 14-3-3 levels in cancer patients. Methods: Two reviewers independently systematically reviewed the Web of Science, Embase, and PubMed databases to identify published, suitable studies through October 2019. The correlation between the level of 14-3-3 and cancer patient survival were assessed based upon pooled HR (hazard ratios) and 95% CI (confidence intervals) derived from chosen studies. Results: In total we were able to identify 22 eligible studies that had enrolled 2676 patients in the present meta-analysis. Assessment of these studies revealed that elevated 14-3-3 level correlated significantly with poorer OS (overall survival) (HR : 1.93, 95% CI : 1.42-2.61) in cancer patients. This was true even when studies were analyzed in subgroups according to tumor type, sample size, analysis type, and method of HR determination. With respect to disease-free survival (DFS), the pooled HR for cancer patients expressing high levels of 14-3-3 was 1.89 (95% CI: 1.56-2.30). Patients with elevated 14-3-3 expression also exhibited reduced CSS (cancer-specific survival) (HR: 3.47, 95% CI: 2.12-5.69).Conclusions: The outcomes indicate that higher level of 14-3-3 correlates with poorer patient prognosis in a range of cancer types.Keywords: Meta-analysis, Prognosis, 14-3-3 Proteins C Continuous...

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Prognostic Significance of microRNA-221/222 Expression in Cancers: Evidence from 1,204 Subjects

The International Journal of Biological Markers ◽

10.5301/jbm.5000058 ◽

2014 ◽

Vol 29 (2) ◽

pp. 129-141 ◽

Cited By ~ 4

Author(s):

Jin Wang ◽

Sha Liu ◽

Guo Ping Sun ◽

Fang Wang ◽

Yan Feng Zou ◽

...

Keyword(s):

Meta Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

Published Data ◽

Cancer Type ◽

Free Survival ◽

Patients With Cancer ◽

Elevated Expression ◽

Strength Of Association

Background The prognostic significance of the expression of the miR-221/222 family in cancer remains controversial. We here performed a meta-analysis of published data investigating the effects of miR-221/222 expression on both overall survival (OS) and disease-free survival (DFS) among patients with cancer. Methods A systematic search of the PubMed, Embase, Cochrane, and CNKI databases was performed with the last search being updated on March 15, 2013. The hazard ratio (HR) and its 95% confidence interval (95% CI) were used to assess the strength of association. Results A total of 17 studies involving 1,204 subjects were included in this meta-analysis. When assessing the prognostic significance of miR-221 expression, the pooled HR was 1.91 (95% CI: 1.28-2.85, p=0.002) for OS and 1.36 (95% CI: 0.88-2.09, p=0.163) for DFS. When assessing the prognostic significance of miR-222 expression, the pooled HR was 2.15 (95% CI: 1.51-3.06, p<0.0001) for OS and 1.37 (95% CI: 0.45-4.13, p=0.581) for DFS. We also found that an elevated miR-221 expression was significantly associated with poor OS when stratifying by ethnicity, cancer type, statistical methodology, sample, and quality assessment. There was no evidence of publication bias. Conclusion The meta-analysis demonstrates that the elevated expression of miR-221 and miR-222 is associated with poor OS in patients with cancer. The miR-221/222 cluster might be used as a potential therapeutic strategy in clinical practice. More work is required to fully elucidate the role of the miR-221/222 family in human tumors.

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Prognostic Role of EGFR/p-EGFR in Patients With Nasopharyngeal Carcinoma: A Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2021.697369 ◽

2021 ◽

Vol 11 ◽

Author(s):

Xishan Chen ◽

Renba Liang ◽

Lin Lai ◽

Kaihua Chen ◽

Xiaodong Zhu

Keyword(s):

Nasopharyngeal Carcinoma ◽

Subgroup Analysis ◽

Meta Analysis ◽

Prognostic Significance ◽

Group Analysis ◽

High Expression ◽

Sensitivity Analyses ◽

Significant Heterogeneity ◽

Free Survival ◽

Egfr Expression

BackgroundThe prognostic value of epidermal growth factor receptor (EGFR)/phosphorylated EGFR (p-EGFR) expression in nasopharyngeal carcinoma remains controversial. A meta-analysis was performed to investigate prognostic significance of EGFR/p-EGFR expression in patients with nasopharyngeal carcinoma.MethodsLiteratures published before November 2020 were systematically searched in relevant databases, including PubMed, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), and Wan fang databases. STATA 13 statistical software was used to analyze the pooled hazard ratio (HR) and 95% confidence interval (CI). Heterogeneity of the studies was examined by I2. Sensitivity and subgroup analysis were performed to explore sources of heterogeneity. The potential publication bias was assessed using both Egger’s and Begg’s tests.ResultsA total of 20 literatures with 1545 patients were included for the meta-analysis. The meta-analysis results suggested that high expression of EGFR was significantly associated with poor overall survival (OS) (HR = 1.70, 95% CI: 1.24–3.15, P = 0.001) and disease-free survival (DFS) (HR = 2.58, 95% CI: 1.87–3.56, P = 0.000). However, it was not significantly associated with progression-free survival (PFS) (HR = 1.85, 95% CI: 0.90–3.82, P = 0.09) and distant metastasis-free survival (DMFS) (HR = 1.39, 95% CI: 0.73–2.67, P = 0.319). The subgroup analysis indicated that patients with EGFR high expression in studies of higher TNM stage (III–IV) ratio had significantly poor OS (HR = 2.27, 95% CI: 1.09–4.73, P = 0.03), but heterogeneity existed in studies (I2 = 95.1%, P = 0.000). Sensitivity analyses revealed that EGFR expression did not significantly affect OS by an individual study solely, indicating there was inherent heterogeneity in OS cohorts. There was no significant heterogeneity among eight studies in the DFS cohorts (I2 = 0%, P = 0.606). There was significant heterogeneity between EGFR expression and DMFS (I2 = 82.8%, P = 0.000). Sub-group analysis in differentiated carcinoma demonstrated a smaller heterogeneity (I2 = 33.2%). In addition, p-EGFR high expression had no significant correlation with OS (HR = 1.00, 95% CI: 0.88–1.14, P = 0.982) and DMFS (HR = 1.21, 95% CI: 0.96–1.52, P = 0.112). The heterogeneity among p-EGFR and OS studies was small (I2 = 21%, P = 0.26). There was no significant heterogeneity in the DMFS cohorts (I2 = 0%, P = 0.497).ConclusionEGFR high-expression was significantly associated with poor OS and DFS, which may serve as a prognostic predictor for nasopharyngeal cancer.Systematic Review Registration[https://www.crd.york.ac.uk/PROSPERO], identifier [number CRD42021258457].

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Prognostic role of high cathepsin D expression in breast cancer: a systematic review and meta-analysis

Therapeutic Advances in Medical Oncology ◽

10.1177/1758835920927838 ◽

2020 ◽

Vol 12 ◽

pp. 175883592092783

Author(s):

Junho Kang ◽

Yeuni Yu ◽

Seongdo Jeong ◽

Hansong Lee ◽

Hye Jin Heo ◽

...

Keyword(s):

Breast Cancer ◽

Subgroup Analysis ◽

Cathepsin D ◽

Poor Prognosis ◽

Early Stage ◽

Meta Analysis ◽

Disease Free Survival ◽

Breast Cancer Prognosis ◽

Cancer Prognosis ◽

Risk Of Relapse

Background: High cathepsin D has been associated with poor prognosis in breast cancer; however, the results of many studies are controversial. Here, we assessed the association between high cathepsin D levels and worse breast cancer prognosis by conducting a meta-analysis. Methods: A comprehensive search strategy was used to search relevant literature in PUBMED and EMBASE by September 2018. The meta-analysis was performed in Review Manager 5.3 using hazard ratios (HRs) with 95% confidence intervals (CIs). Results: A total of 15,355 breast cancer patients from 26 eligible studies were included in this meta-analysis. Significant associations between elevated high cathepsin D and poor overall survival (OS) (HR = 1.61, 95% CI: 1.35–1.92, p < 0.0001) and disease-free survival (DFS) (HR = 1.52, 95% CI: 1.31–2.18, p < 0.001) were observed. In the subgroup analysis for DFS, high cathepsin D was significantly associated with poor prognosis in node-positive patients (HR = 1.38, 95% CI: 1.25–1.71, p < 0.00001), node-negative patients (HR = 1.78, 95% CI: 1.39–2.27, p < 0.0001), early stage patients (HR = 1.73, 95% CI: 1.34–2.23, p < 0.0001), and treated with chemotherapy patients (HR = 1.60, 95% CI: 1.21–2.12, p < 0.001). Interestingly, patients treated with tamoxifen had a low risk of relapse when their cathepsin D levels were high (HR = 0.71, 95% CI: 0.52–0.98, p = 0.04) and a high risk of relapse when their cathepsin D levels were low (HR = 1.50, 95% CI: 1.22–1.85, p = 0.0001). Conclusions: Our meta-analysis suggests that high expression levels of cathepsin D are associated with a poor prognosis in breast cancer. Based on our subgroup analysis, we believe that cathepsin D can act as a marker for poor breast cancer prognosis and also as a therapeutic target for breast cancer.

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Overexpression of lncRNA SNGH3 Predicts Unfavorable Prognosis and Clinical Outcomes in Human Cancers: Evidence from a Meta-Analysis

BioMed Research International ◽

10.1155/2020/7974034 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Yaofei Jiang ◽

Lulu Le

Keyword(s):

Clinical Outcomes ◽

Histological Grade ◽

Meta Analysis ◽

Disease Free Survival ◽

The Cancer Genome Atlas ◽

Cochrane Library ◽

Cancer Type ◽

Free Survival ◽

Human Cancers ◽

Tcga Dataset

Long noncoding RNAs (lncRNAs) have been confirmed to play a crucial role in human disease, especially in tumor development and progression. Small nucleolar RNA host gene (SNHG3), a newly identified lncRNA, has been found dysregulated in various cancers. Nevertheless, the results remain controversial. Thus, we aim to analyze the comprehensive data to elaborate the association between SNHG3 expression and clinical outcomes in multiple cancers. We searched PubMed, Web of Science, Cochrane Library, Embase, and MEDLINE database to identify eligible articles. STATA software was applied to calculate the hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (95% CI) for survival outcomes and clinical parameters, respectively. Besides, the data from The Cancer Genome Atlas (TCGA) dataset was extracted to verify the results in our meta-analysis. There were thirteen studies totaling 919 cancer patients involved in this meta-analysis. The results demonstrated that high SNHG3 expression was significantly associated with poor overall survival (OS) (HR=2.53, 95% CI: 1.94-3.31) in cancers, disease-free survival (DFS) (HR=3.89, 95% CI: 1.34-11.3), and recurrence-free survival (RFS) (HR=2.42, 95% CI: 1.14-5.15) in hepatocellular carcinoma. Analysis stratified by analysis method, sample size, follow-up time, and cancer type further verified the prognostic value of SNHG3. Additionally, patients with high SNHG3 expression tended to have more advanced clinical stage, higher histological grade, earlier distant metastasis, and earlier lymph node metastasis. Excavation of TCGA dataset valuated that SNHG3 was upregulated in various cancers and predicted worse OS and DFS. Overexpressed SNHG3 was strongly associated with poor survival and clinical outcomes in human cancers and therefore can serve as a promising biomarker for predicting patients’ prognosis.

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Prognostic Value of MicroRNA-182 in Cancers: A Meta-Analysis

Disease Markers ◽

10.1155/2015/482146 ◽

2015 ◽

Vol 2015 ◽

pp. 1-8 ◽

Cited By ~ 9

Author(s):

Fei Wang ◽

Shanliang Zhong ◽

Haijun Zhang ◽

Wei Zhang ◽

Hongming Zhang ◽

...

Keyword(s):

Prognostic Value ◽

Meta Analysis ◽

Disease Free Survival ◽

Cancer Prognosis ◽

Relapse Free Survival ◽

Altered Expression ◽

Free Survival ◽

Chinese Populations ◽

Hazard Ratios ◽

Disease Free

Objective. MicroRNA-182 (miR-182) exhibits altered expression in various cancers. The aim of this study was to investigate the predictive value of miR-182 expression for cancer patient survival.Methods. Eligible studies were identified through multiple search strategies, and the hazard ratios (HRs) for patient outcomes were extracted and estimated. A meta-analysis was performed to evaluate the prognostic value of miR-182.Results. In total, 14 studies were included. A high miR-182 expression level predicted a worse outcome with a pooled HR of 2.18 (95% CI: 1.53–3.11) in ten studies related to overall survival (OS), especially in Chinese populations. The results of seven studies evaluating disease-free survival/relapse-free survival/recurrence-free interval/disease-specific survival (DFS/RFS/RFI/DSS) produced a pooled HR of 1.77 (95% CI: 0.91–3.43), which was not statistically significant; however, the trend was positive. When disregarding the DSS from one study, the expression of miR-182 was significantly correlated with DFS/RFS/RFI (pooled HR = 2.52, 95% CI: 1.67–3.79).Conclusions. High miR-182 expression is associated with poor OS and DFS/RFS/RFI in some types of cancers, and miR-182 may be a useful prognostic biomarker for predicting cancer prognosis. However, given the current insufficient relevant data, further clinical studies are needed.

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