Discovery and function exploration of microRNA-155 as a molecular biomarker for early detection of breast cancer

Abstract Background MicroRNA-155 (miR-155) may function as a diagnostic biomarker of breast cancer (BC). Nevertheless, the available evidence is controversial. Therefore, we performed this study to summarize the global predicting role of miR-155 for early detection of BC and preliminarily explore the functional roles of miR-155 in BC. Methods We first collected published studies and applied the bivariate meta-analysis model to generate the pooled diagnostic parameters of miR-155 in diagnosing BC such as sensitivity, specificity and area under curve (AUC). Then, we applied function enrichment and protein–protein interactions (PPI) analyses to explore the potential mechanisms of miR-155. Results A total of 21 studies were finally included. The results indicated that miR-155 allowed for the discrimination between BC patients and healthy controls with a sensitivity of 0.87 (95% CI 0.78–0.93), specificity of 0.82 (0.72–0.89), and AUC of 0.91 (0.88–0.93). In addition, the overall sensitivity, specificity and AUC for circulating miR-155 were 0.88 (0.76–0.95), 0.83 (0.72–0.90), and 0.92 (0.89–0.94), respectively. Function enrichment analysis revealed several vital ontologies terms and pathways associated with BC occurrence and development. Furthermore, in the PPI network, ten hub genes and two significant modules were identified to be involved in some important pathways associated with the pathogenesis of BC. Conclusions We demonstrated that miR-155 has great potential to facilitate accurate BC detection and may serve as a promising diagnostic biomarker for BC. However, well-designed cohort studies and biological experiments should be implemented to confirm the diagnostic value of miR-155 before it can be applied to routine clinical procedures.

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Diagnostic value of RASSF1A methylation for breast cancer: a meta-analysis

Bioscience Reports ◽

10.1042/bsr20190923 ◽

2019 ◽

Vol 39 (6) ◽

Cited By ~ 4

Author(s):

Mingyi Li ◽

Chunpeng Wang ◽

Binbin Yu ◽

Xueyuan Zhang ◽

Fang Shi ◽

...

Keyword(s):

Breast Cancer ◽

Meta Analysis ◽

Characteristic Curve ◽

High Specificity ◽

Diagnostic Odds Ratio ◽

Diagnostic Value ◽

Cochrane Library ◽

Diagnostic Biomarker ◽

Summary Receiver Operating Characteristic ◽

Rassf1a Methylation

Abstract Background: Numerous studies reported that RAS-association domain family 1 isoform A (RASSF1A) methylation might act as diagnostic biomarker for breast cancer (BC), this meta-analysis aimed to evaluate the value of RASSF1A methylation for diagnosing BC. Methods: Such databases as PubMed, Cochrane Library and Web of Science databases were searched for literatures until May 2019. A meta-analysis was performed utilizing STATA and Revman softwares. Furthermore, subgroup analysis was adopted to determine likely sources of heterogeneity. Results: Totally 19 literatures with 1849 patients and 1542 controls were included in the present study. Sensitivity, specificity, diagnostic odds ratio (DOR) and the area under the summary receiver operating characteristic curve (AUC) of RASSF1A methylation for diagnosing BC were 0.49, 0.95, 19.0 and 0.83, respectively. The sensitivity (0.54 vs 0.43), DOR (30.0 vs 10.0) and AUC (0.84 vs 0.81) of RASSF1A methylation in Caucasian were higher than other ethnicities. The sensitivity (0.64 vs 0.57), DOR (21.0 vs 14.0) and AUC (0.89 vs 0.86) of methylation-specific PCR (MSP) were superior to other methods (q-MSP, OS-MSP and MethyLight). The sensitivity, DOR and AUC of serum RASSF1A methylation vs RASSF1A methylation in other samples (tissue or plasma) were 0.55 vs 0.40, 22.0 vs 14.0 and 0.86 vs 0.74, respectively. Conclusions: RASSF1A methylation might be a potential diagnostic biomarker for BC. Considering its low sensitivity and high specificity, it should combine with others to upgrade the sensitivity. Besides, under such conditions, MSP detection, serum RASSF1A methylation and Caucasian are shown to be more effective and suitable for diagnosing BC.

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Potential Role of MicroRNA-375 as Biomarker in Human Cancers Detection: A Meta-Analysis

BioMed Research International ◽

10.1155/2017/1875843 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 3

Author(s):

Jin Yan ◽

Qiang She ◽

Xiaoran Shen ◽

Yifeng Zhang ◽

Bingtuan Liu ◽

...

Keyword(s):

Test Performance ◽

Meta Analysis ◽

Area Under The Curve ◽

Diagnostic Odds Ratio ◽

Diagnostic Value ◽

Circulating Microrna ◽

Cancer Type ◽

Analysis Model ◽

Summary Receiver Operating Characteristic ◽

Sensitivity Specificity

The association between circulating microRNA-375 (miR-375) expression and cancers has been studied; however, the results are inconsistent. We searched PubMed, Embase, and Web of Science for studies concerning the diagnostic value of miR-375 for cancer. The bivariate meta-analysis model was employed to summarize sensitivity, specificity, and diagnostic odds ratio (DOR) for miR-375 in the diagnosis of cancer. Summary receiver operating characteristic (SROC) curve analysis and the area under the curve (AUC) were also used to check the overall test performance. A total of 645 cancer patients and 421 cancer-free individuals from 12 studies were contained in this meta-analysis. The summary estimates revealed that the pooled sensitivity was 78% (95% confidence interval (CI): 64%–87%), the specificity was 74% (95% CI: 62%–84%), the DOR was 10.04 (95% CI: 6.01–16.77), and the AUC was 0.82 (95% CI: 0.79–0.85). In addition, we found that the diagnostic effect of miR-375 varies according to the race and cancer type. Our data suggest that miR-375 profiling has a potential to be used as a screening test for cancers but the specific race and cancer should be considered. More studies on the diagnostic value of miR-375 for cancer are needed in the future.

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Evaluation of alpha-l-fucosidase for the diagnosis of hepatocellular carcinoma based on meta-analysis

LaboratoriumsMedizin ◽

10.1515/labmed-2019-0152 ◽

2020 ◽

Vol 0 (0) ◽

Cited By ~ 1

Author(s):

Lei Xi ◽

Chunqing Yang

Keyword(s):

Hepatocellular Carcinoma ◽

Operating Characteristic ◽

Meta Analysis ◽

Area Under The Curve ◽

Diagnostic Odds Ratio ◽

Diagnostic Value ◽

Receiver Operating Characteristic Curves ◽

Sensitivity Specificity ◽

Review Manager

AbstractObjectivesThe main aim of the present study was to assess the diagnostic value of alpha-l-fucosidase (AFU) for hepatocellular carcinoma (HCC).MethodsStudies that explored the diagnostic value of AFU in HCC were searched in EMBASE, SCI, and PUBMED. The sensitivity, specificity, and DOR about the accuracy of serum AFU in the diagnosis of HCC were pooled. The methodological quality of each article was evaluated with QUADAS-2 (quality assessment for studies of diagnostic accuracy 2). Receiver operating characteristic curves (ROC) analysis was performed. Statistical analysis was conducted by using Review Manager 5 and Open Meta-analyst.ResultsEighteen studies were selected in this study. The pooled estimates for AFU vs. α-fetoprotein (AFP) in the diagnosis of HCC in 18 studies were as follows: sensitivity of 0.7352 (0.6827, 0.7818) vs. 0.7501 (0.6725, 0.8144), and specificity of 0.7681 (0.6946, 0.8283) vs. 0.8208 (0.7586, 0.8697), diagnostic odds ratio (DOR) of 7.974(5.302, 11.993) vs. 13.401 (8.359, 21.483), area under the curve (AUC) of 0.7968 vs. 0.8451, respectively.ConclusionsAFU is comparable to AFP for the diagnosis of HCC.

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The diagnostic value of EBV-DNA and EBV-related antibodies detection for nasopharyngeal carcinoma: a meta-analysis

Cancer Cell International ◽

10.1186/s12935-021-01862-7 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Weixing Liu ◽

Gui Chen ◽

Xin Gong ◽

Yingqi Wang ◽

Yaoming Zheng ◽

...

Keyword(s):

Nasopharyngeal Carcinoma ◽

Test Performance ◽

Meta Analysis ◽

Diagnostic Value ◽

Cochrane Library ◽

Control Group ◽

Summary Receiver Operating Characteristic ◽

Ebv Dna ◽

The Difference ◽

Sensitivity Specificity

Abstract Background Numerous individual studies have investigated the diagnostic value of EBV-DNA, EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG detection for nasopharyngeal carcinoma (NPC), but the conclusions remain controversial. This meta-analysis aimed to determine the value of EBV-DNA, EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG detection in the diagnosis of NPC. Methods PROSPERO registration number: CRD42019145532. PubMed, EMBASE, Cochrane Library, and Chinese data libraries (Wanfang, CNKI, and CBM) were searched up to January 2019. The pooled sensitivity, specificity, and positive likelihood, negative likelihood, and diagnostic odds ratios were conducted in this meta-analysis. Summary receiver operating characteristic curves evaluated the test-performance global summary. Publication bias was examined by Deek’s funnel plot asymmetry test. Results Forty-seven studies with 8382 NPC patients (NPC group) and 15,089 individuals without NPC (Control group) were included in this meta-analysis. The sensitivity, specificity, positive likelihood (+ LR), negative likelihood (-LR), DOR and AUC of EBV-DNA in diagnosis of NPC were: 0.76 (95% CI 0.73–0.77), 0.96 (95% CI 0.95–0.97), 14.66 (95% CI 9.97–21.55), 0.19 (95% CI 0.13–0.28), 84 (95% CI 50.45–139.88), 0.96 (SE: 0.001), and 0.55 (95% CI 0.54–0.57), 0.96 (95% CI 0.96–0.97), 12.91 (95% CI 9.55–17.45), 0.35 (95% CI 0.29–0.43), 39.57 (95% CI 26.44–59.23), 0.94 (SE: 0.002) for the EA-IgA, and 0.85 (95% CI 0.84–0.85), 0.89 (95% CI 0.88–0.89), 6.73 (95% CI5.38–8.43), 0.17 (95% CI 0.12–0.23), 43.03 (95% CI 31.51–58.76), 0.93 (SE: 0.007) for the VCA-IgA, and 0.86 (95% CI 0.85–0.88), 0.87 (95% CI 0.88–0.90), 7.55 (95% CI 5.79–9.87), 0.16 (95% CI 0.13–0.19), 50.95 (95% CI 34.35–75.57), 0.94 (SE: 0.008) for the EBNA1-IgA, and 0.70 (95% CI 0.69–0.71), 0.94 (95% CI 0.94–0.95), 9.84 (95% CI 8.40–11.54), 0.25 (95% CI 0.21–0.31), 40.59 (95% CI 32.09–51.35), 0.95 (SE: 0.005) for the Rta-IgG. The EBV-DNA had larger AUC compared with other EBV-based antibodies (P < 0.05), while the difference between EA-IgA, VCA-IgA, EBNA1-IgA and Rta-IgG was not statistically significant (P > 0.05). Conclusions EBV-DNA, VCA-IgA, EBNA1-IgA and Rta-IgG detection have high accuracy in early diagnosis NPC. In addition, EBV-DNA detection has the higher diagnosis accuracy in NPC. On the other hand, EA-IgA is suitable for the diagnosis but not NPC screening.

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Comparison of conventional, doppler and contrast-enhanced ultrasonography in differential diagnosis of ovarian masses: a systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2021-052830 ◽

2021 ◽

Vol 11 (12) ◽

pp. e052830

Author(s):

Lizhang Xun ◽

Lamei Zhai ◽

Hui Xu

Keyword(s):

Systematic Review ◽

Ovarian Cancer ◽

Data Extraction ◽

Meta Analysis ◽

Diagnostic Value ◽

Doppler Us ◽

Contrast Enhanced ◽

Contrast Enhanced Ultrasonography ◽

Sensitivity Specificity ◽

Ovarian Masses

ObjectivesTo assess the value of conventional, Doppler and contrast-enhanced ultrasonography (CEUS) (conventional ultrasonography (US), Doppler US and CEUS) for diagnosing ovarian cancer.DesignSystematic review and meta-analysis.Data sourcesPubMed, Embase and the Cochrane Library were conducted for studies published until October 2021.Eligibility criteriaStudies assessed the diagnostic value of conventional US, Doppler US or CEUS for detecting ovarian cancer, with no restrictions placed on published language and status.Data extraction and synthesisThe study selection and data extraction were performed by two independent authors. The sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), diagnostic OR (DOR) and area under the receiver operating characteristic curve (AUC) were pooled using the bivariate generalised linear mixed model and random effects model.ResultsThe meta-analysis included 72 studies and involved 9296 women who presented with ovarian masses. The pooled sensitivity, specificity, PLR, NLR, DOR and AUC for conventional US were 0.91 (95% CI: 0.87 to 0.94) and 0.87 (95% CI: 0.82 to 0.91), 6.87 (95% CI: 4.98 to 9.49) and 0.10 (95% CI: 0.07 to 0.15), 57.52 (95% CI: 36.64 to 90.28) and 0.95 (95% CI: 0.93 to 0.97), respectively. The sensitivity, specificity, PLR, NLR, DOR and AUC for Doppler US were 0.93 (95% CI: 0.91 to 0.95) and 0.85 (95% CI: 0.80 to 0.89), 6.10 (95% CI: 4.59 to 8.11) and 0.08 (95% CI: 0.06 to 0.11), 61.76 (95% CI: 39.99 to 95.37) and 0.96 (95% CI: 0.94 to 0.97), respectively. The pooled sensitivity, specificity, PLR, NLR, DOR and AUC for CEUS were 0.97 (95% CI: 0.92 to 0.99) and 0.92 (95% CI: 0.85 to 0.95), 11.47 (95% CI: 6.52 to 20.17) and 0.03 (95% CI: 0.01 to 0.09), 152.11 (95% CI: 77.77 to 297.51) and 0.99 (95% CI: 0.97 to 0.99), respectively. Moreover, the AUC values for conventional US (p=0.002) and Doppler US (p=0.005) were inferior to those of CEUS.ConclusionsConventional US, Doppler US and CEUS have a relatively high differential diagnostic value for differentiating between benign and malignant ovarian masses. The diagnostic performance of CEUS was superior to that of conventional US and Doppler US.

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Identification of differentially methylated genes as diagnostic and prognostic biomarkers of breast cancer

World Journal of Surgical Oncology ◽

10.1186/s12957-021-02124-6 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Xiao-hong Mao ◽

Qiang Ye ◽

Guo-bing Zhang ◽

Jin-ying Jiang ◽

Hong-ying Zhao ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Diagnosis ◽

High Sensitivity ◽

Breast Cancer Diagnosis ◽

Diagnostic Value ◽

Methylation Pattern ◽

Clinical Value ◽

Roc Curve Analysis ◽

Differentially Methylated Genes ◽

Sensitivity Specificity

Abstract Background Aberrant DNA methylation is significantly associated with breast cancer. Methods In this study, we aimed to determine novel methylation biomarkers using a bioinformatics analysis approach that could have clinical value for breast cancer diagnosis and prognosis. Firstly, differentially methylated DNA patterns were detected in breast cancer samples by comparing publicly available datasets (GSE72245 and GSE88883). Methylation levels in 7 selected methylation biomarkers were also estimated using the online tool UALCAN. Next, we evaluated the diagnostic value of these selected biomarkers in two independent cohorts, as well as in two mixed cohorts, through ROC curve analysis. Finally, prognostic value of the selected methylation biomarkers was evaluated breast cancer by the Kaplan-Meier plot analysis. Results In this study, a total of 23 significant differentially methylated sites, corresponding to 9 different genes, were identified in breast cancer datasets. Among the 9 identified genes, ADCY4, CPXM1, DNM3, GNG4, MAST1, mir129-2, PRDM14, and ZNF177 were hypermethylated. Importantly, individual value of each selected methylation gene was greater than 0.9, whereas predictive value for all genes combined was 0.9998. We also found the AUC for the combined signature of 7 genes (ADCY4, CPXM1, DNM3, GNG4, MAST1, PRDM14, ZNF177) was 0.9998 [95% CI 0.9994–1], and the AUC for the combined signature of 3 genes (MAST1, PRDM14, and ZNF177) was 0.9991 [95% CI 0.9976–1]. Results from additional validation analyses showed that MAST1, PRDM14, and ZNF177 had high sensitivity, specificity, and accuracy for breast cancer diagnosis. Lastly, patient survival analysis revealed that high expression of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 were significantly associated with better overall survival. Conclusions Methylation pattern of MAST1, PRDM14, and ZNF177 may represent new diagnostic biomarkers for breast cancer, while methylation of ADCY4, CPXM1, DNM3, PRDM14, PRKCB, and ZNF177 may hold prognostic potential for breast cancer.

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Circular RNA hsa_circ_0005046 and hsa_circ_0001791 May Become Diagnostic Biomarkers for Breast Cancer Early Detection

Journal of Oncology ◽

10.1155/2021/2303946 ◽

2021 ◽

Vol 2021 ◽

pp. 1-7

Author(s):

Melika Ameli-Mojarad ◽

Mandana Ameli-Mojarad ◽

Mitra Nourbakhsh ◽

Ehsan Nazemalhosseini-Mojarad

Keyword(s):

Breast Cancer ◽

Roc Curve ◽

Expression Profiles ◽

Circular Rna ◽

Diagnostic Value ◽

High Expression ◽

Expression Level ◽

Diagnostic Biomarker ◽

Expression Levels ◽

Normal Tissues

Breast cancer (BC) is one of the most common lethal diseases in women worldwide. Recent evidence has shown that covalently closed Circular RNA (circRNA) deregulation is observed in different human malignancies and cancers. Lately, circRNAs are being considered as a new diagnostic biomarker; however, the mechanism and the correlation of action between circRNAs and BC are still unclear. In the present study, we try to investigate the expression level of hsa_circ_0005046 and hsa_circ_0001791 in BC. By using quantitative real-time polymerase chain reaction (qRT-PCR), expression profiles of candidate circRNAs were detected in 60 BC tissue and paired adjacent normal tissues. Furthermore, the clinicopathological relation and diagnostic value were estimated. Our results showed the higher expression levels of hsa_circ_0005046 and hsa_circ_0001791 in BC tissues compared to paired adjacent normal tissues with P value ( P < 0.0001 ) for both circRNAs, and the area under the receiver operating characteristic (ROC) curve was 0.857 and 1.0, respectively; in addition, a total 10 miRNAs that can be targeted by each candidate circRNAs was predicted base on bioinformatics databases. Taken together, for the first time, the results of our study presented high expression levels of hsa_circ_0005046 and hsa_circ_00017916 in BC; although there was no direct correlation between the high expression level of both circRNAs with clinic pathological factors, except hsa_circ_0001791 association with estrogen receptors (ER), high ROC curve in expressed samples indicated that both circRNAs could be used as a new diagnostic biomarker for BC. Moreover, miRNAs selection tools predicted that miR-215 and mir-383-5p which have a tumor suppressor role in BC can be targeted by our candidate circRNAs to affect the PI3K/AKT pathway; in conclusion, further studies are required to validate the oncogene role of our candidate circRNAs through the PI3k pathway.

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Diagnostic Value of sST2 in Cardiovascular Diseases: A Systematic Review and Meta-Analysis

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.697837 ◽

2021 ◽

Vol 8 ◽

Author(s):

Tianyi Zhang ◽

Chengyang Xu ◽

Rui Zhao ◽

Zhipeng Cao

Keyword(s):

Myocardial Infarction ◽

Cardiac Troponin ◽

Weighted Mean Difference ◽

Meta Analysis ◽

Diagnostic Value ◽

Mean Difference ◽

Diagnostic Biomarker ◽

Healthy Individuals ◽

Weighted Mean ◽

Standard Mean Difference

Biomarkers such as B-type natriuretic peptide (BNP), N-terminal pro-BNP (NT-proBNP), cardiac troponin (cTn), and CK-MB contribute significantly to the diagnosis of cardiovascular disease (CVD). Recent studies have demonstrated that suppression of tumorigenicity 2 (ST2) is associated with CVD, but a meta-analysis of ST2 levels in different CVDs has yet to be conducted. Therefore, the present study aimed to investigate soluble ST2 (sST2) levels in patients with ischemic heart disease (IHD), myocardial infarction (MI), and heart failure (HF). A total of 1,425 studies were searched across four databases, of which 16 studies were included in the meta-analysis. The Newcastle–Ottawa Quality Assessment Scale (NOS) values of all 16 studies were ≥7. The meta-analysis results indicated that the sST2 level was not correlated with IHD (standard mean difference [SMD] = 0.58, 95% confidence interval [95% CI] = 0.00 to 1.16, p = 0.05) or MI (weighted mean difference [WMD] = 0.17, 95% CI = −0.22 to 0.55, p = 0.40) but was significantly associated with HF (WMD = 0.21, 95% CI = 0.04 to 0.38, p = 0.02; I2 = 99%, p < 0.00001). sST2 levels did not differ significantly between patients with IHD or MI and healthy individuals; however, we believe that ST2 could be used as an auxiliary diagnostic biomarker of HF.

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MRI and bone scintigraphy for breast cancer bone metastase: a meta-analysis

Open Medicine ◽

10.1515/med-2019-0029 ◽

2019 ◽

Vol 14 (1) ◽

pp. 317-323 ◽

Cited By ~ 1

Author(s):

Yue Rong ◽

Hong Ren ◽

Xianjun Ding

Keyword(s):

Breast Cancer ◽

Magnetic Resonance ◽

Comparative Study ◽

Bone Metastases ◽

Bone Scintigraphy ◽

Magnetic Resonance Image ◽

Meta Analysis ◽

Diagnostic Value ◽

Satisfactory Method ◽

The Comparative Study

AbstractObjectiveThe aim of this study was to compare the diagnostic value of magnetic resonance image (MRI) and bone scintigraphy (BS) in the diagnosis of breast cancer bone metastases.MethodsSearching in the databases including PubMed, Embase about the comparative study of MRI and bone scintigraphy in the diagnosis of breast cancer bone metastases during 2000~2018. After we screened further, the extracted effective data were calculated by Meta-Disc 1.4 software.ResultsWe obtained 4 articles. The pooled estimates for sensitivity of MRI, BS were 0.99 (95% CI, [0.95, 1.00]) and 0.93 (95% CI, [0.88, 0.97]) respectively; For specificity were 0.99 (95% CI, [0.95, 1.00]) and 0.86 (95% CI, [0.79, 0.92]) respectively. The AUC of SROC curve for MRI and BS were 0.9948 and 0.9675 respectively.ConclusionMRI remains to be a satisfactory method for the diagnosis of breast cancer bone metastases and should first be considered for patients.

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