SPP1 Might Be A Novel Prognostic Biomarker For Patients With Malignancy: A Meta-Analysis And Sequential Verification Based on Bioinformatic Analysis

Abstract Background: Several studies have investigated the relationship between secreted phosphoprotein 1 (SPP1) expression level and prognosis of various tumors, but the results are far from conclusive. Therefore, we performed the present meta-analysis to investigate the prognostic value of SPP1 in pan-cancer. Furthermore, a followed confirmation based on The Cancer Genome Atlas (TCGA) database was also performed to verify our results.Methods: We performed a systematic search from PubMed, Embase, Web of Science, and Cochrane Library databases and 19 articles, including 3403 patients and 9 types of tumors, were pooled in our meta-analysis. Overall survival (OS) and disease-free survival (DFS), which correlated with SPP1 expression, were considered as the primary outcome. Subgroup analyses, sensitivity analysis, and publication bias were used to investigate heterogeneity and reliability of the results. Furthermore, we also explored the relationship between SPP1 expression and clinical parameters of tumor patients. Finally, the results were verified with TCGA database and we further explored the relationship between SPP1 expression and tumor immuno-microenvironment (TIME), DNA methylation, and enriched gene pathway.Results: Our meta-analysis showed that high-expressed SPP1 was significantly related to poor OS and DFS in various cancers, especially in liver hepatocellular carcinoma (LIHC). Furthermore, we also identified that the high expression level of SPP1 was significantly correlated with tumor grade. The expression level of SPP1 in the majority of tumor types were much higher than the corresponding normal tissues analyzed from databases. Besides, we also observed that high-expressed SPP1 was related to poor OS and DFS in LIHC, which supported the conclusion of meta-analysis. In addition, high-expressed SPP1 is related to 6 immune cells in TIME and DNA methylation regulatory genes. Ultimately, the results of Gene Set Enrichment Analysis (GSEA) suggested that tumor-related gene sets, such as hypoxia and lipid metabolism, were significantly enriched in high-expressed SPP1 group.Conclusions: SPP1 is high-expressed in various tumor tissues and correlated with poor prognosis. SPP1 might promote cancer invasion and metastasis by affecting tumor grade, TIME, DNA methylation, hypoxia, and lipid metabolism. SPP1 is expected to become a new clinical indicator for tumor detection and prognosis, and provide a new idea for tumor targeted therapy.

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SPP1 Might Be a Novel Prognostic Biomarker for Patients With Malignancy: a Meta-analysis and Sequential Verification Based on Bioinformatic Analysis

10.21203/rs.3.rs-132455/v1 ◽

2020 ◽

Author(s):

Hao-ran Zheng ◽

Ai-Min Jiang ◽

Na Liu ◽

Qian-Qian Ding ◽

Fu-Mei Zhao ◽

...

Keyword(s):

Dna Methylation ◽

Lipid Metabolism ◽

Meta Analysis ◽

Disease Free Survival ◽

Tumor Grade ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Expression Level ◽

Cochrane Library ◽

The Relationship

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Prognostic and clinicopathological significance of YAP in Colorectal carcinoma: A systematic review and meta-analysis

10.21203/rs.3.rs-33708/v1 ◽

2020 ◽

Author(s):

Lu Dai ◽

Xiao Jin ◽

Jiayan Wang ◽

Yilan Ma ◽

Haihao Yan ◽

...

Keyword(s):

Meta Analysis ◽

Great Influence ◽

Tumor Location ◽

Clinicopathological Features ◽

Expression Level ◽

Cochrane Library ◽

Hazard Ratios ◽

Clinicopathological Significance ◽

Prediction Of Prognosis ◽

The Relationship

Abstract Background: YAP is a protein encoded by the YAP gene in humans. Numerous studied showed that YAP expressed in colorecal carcinoma (CRC) and has a association with poor clinical outcomes. However, the association between YAP expression level with prognostic and clinicopathological features in CRC patients remains unclear. Therefore, we performed a meta-analysis to investigate the prognostics effect of YAP expression on CRC patients.Methods: A systematic search of the PubMed, Web of Science, Cochrane Library and Embase databases was conducted based on predefined selection criteria in April 26, 2020. The correlation between YAP expression level and survival outcomes or clinicopathological characteristic was analyzed by hazard ratios (HR) or odds ratios (OR) at 95% confdence intervals (CI).Results: 12 studies were included, with a total of 2286 CRC patients,in our meta-analysis.the results show the relationship between YAP expression level with overall survival (OS) in CRC patients HR (2.02, 95%CI 1.67-2.44 I2 =19.7% P= 0.25) . In addition to clinicpathological features, CRC patients with overexpression of YAP were tend to advanced TNM stage(OR:2.99, 95%CI 2.11-4.25, I2=0.0%, P=0.699), lymph node metastasis(OR:3.73, 95% CI 2.63-5.30, I2=4.8%, P=0.386), distant metastasis(OR:3.03, 95% CI 1.21-7.56, I2=65.3%, P=0.021), tumor invasion depth HR (2.82 95%CI 1.65-4.83 I2=0.0%, p=0.413), but have no associated with sex, tumor size, tumor location and tumor differentiation.Conclusion: The results of this meta-analysis show that high expression of YAP tended to have a worse progosis and have great influence on clinicpathological features. which means YAP may serve as a promising indicator in the prediction of prognosis and clinicopathological features in CRC patients.

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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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TP73-AS1 as a Predictor of Clinicopathological Parameters and Prognosis in Human Malignancies: A Meta and Bioinformatics Analysis

10.21203/rs.3.rs-1124245/v1 ◽

2021 ◽

Author(s):

Caizhi Chen ◽

Jingjing Wang ◽

Yeqian Feng ◽

Ye Liang ◽

Yan Huang ◽

...

Keyword(s):

Prognostic Value ◽

Meta Analysis ◽

Disease Free Survival ◽

The Cancer Genome Atlas ◽

Prognostic Indicators ◽

Cochrane Library ◽

Clinicopathological Parameters ◽

Oncogenic Signaling ◽

Poor Overall Survival ◽

The Cochrane Library

Abstract Background: LncRNA TP73-AS1 is dysregulated in various tumors but the correlation between its expression and clinicopathological parameters and/or prognoses in cancer patients is inconclusive. Here, we performed a meta-analysis to evaluate the prognostic value of lncRNA TP73-AS1 for malignancies.Methods: We systematically searched four online databases including PubMed, the Web of Science, Embase, and the Cochrane Library for eligible articles published up to June 29/2020. Odds ratios (ORs) and Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used to assess the association of TP73-AS1 expression with prognostic and clinicopathological parameters. We further validated TP73-AS1 expression in various malignancies and its potential prognostic value using the GEPIA online database. We predicted potential biological processes and relevant signal mechanisms through the public databases.Results: A total of 26 studies including 1770 patients were analyzed to evaluate the relationship between TP73-AS1 expression, clinicopathological features and prognostic indicators. The results indicated that TP73-AS1 expression markedly correlates with TNM stage, tumor size, lymph node metastasis and distant metastasis. No correlation with age, gender or differentiation was observed. TP73-AS1 overexpression was a biomarker of poor Overall survival (OS) and Disease-Free-Survival (DFS). Dysregulated TP73-AS1 expression and its prognostic value in various cancers was validated based on The Cancer Genome Atlas (TCGA). Further biological function predictions indicated that TP73-AS1 was involved in pro-oncogenic signaling.Conclusions: The upregulation of LncRNA TP73-AS1 was related to detrimental clinicopathological parameters and can be considered an indicator of poor prognosis for cancer malignancies.

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Renal cell carcinoma: a systematic review and meta-analysis on expression of androgen receptor

Biomedical Research and Therapy ◽

10.15419/bmrat.v5i11.500 ◽

2018 ◽

Vol 5 (11) ◽

pp. 2820-2826

Author(s):

Hossein Abdi ◽

Hamid Reza Mozaffari ◽

Mehrdad Payandeh ◽

Edris Sadeghi

Keyword(s):

Androgen Receptor ◽

Web Of Science ◽

Meta Analysis ◽

Tumor Grade ◽

Cochrane Library ◽

Low Grade ◽

Version 2.0 ◽

Role Of It ◽

The Relationship

Background: Chromosome Xq11-12 is the place that the androgen receptor (AR) sequence appears. Herein, the prevalence of this biomarker and its relation with pT stage and tumor grade was reported. Methods: Four online sites (PubMed, Scopus, Web of Science, and Cochrane Library) have been searched up to Sep 2018 systematically. Meta-Analysis software version 2.0 (CMA 2.0) and STATA 14.0 statistical software were utilized. Publication bias did not exist. Results: From the initial 1141 articles identified from the systematically searches. At last, nine of them remained for analysis. The meta-analysis included 1447 patients that 345 of them had AR expression. AR expression significantly correlated with low tumor grade and low tumor pT stage. Conclusion: AR expression was 28.2%, and it had the relationship with tumor low grade and low pT stage. Additional studies required to figure out the role of it on RCC patients.

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Overexpression of SHMT2 Predicts a Poor Prognosis and Promotes Tumor Cell Growth in Bladder Cancer

Frontiers in Genetics ◽

10.3389/fgene.2021.682856 ◽

2021 ◽

Vol 12 ◽

Author(s):

Peng Zhang ◽

Qian Yang

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Bladder Cancer ◽

Disease Free Survival ◽

Enrichment Analysis ◽

Tumor Grade ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Normal Bladder

SHMT2 was overexpressed in many tumors, however, the role of SHMT2 in bladder cancer (BLCA) remains unclear. We first analyzed the expression pattern of SHMT2 in BLCA using the TNMplot, Oncomine, the Cancer Genome Atlas (TCGA), and the Gene Expression Omnibus (GEO) databases. Next, the association between SHMT2 expression and overall survival (OS)/disease-free survival (DFS) in BLCA patients were analyzed using TCGA and PrognoScan database. The correlation between SHMT2 expression and clinicopathology was determined using TCGA database. Furthermore, the genes co-expressed with SHMT2 and their underlying molecular function in BLCA were explored based on the Oncomine database, Metascape and gene set enrichment analysis (GSEA). Finally, the effects of SHMT2 on cell proliferation, cell cycle, and apoptosis were assessed using in vitro experiments. As a results, SHMT2 was significantly overexpressed in BLCA tissues and cells compared to normal bladder tissues and cells. A high SHMT2 expression predicts a poor OS of BLCA patients. In addition, SHMT2 expression was higher in patients with a high tumor grade and in those who were older than 60 years. However, the expression of SHMT2 was not correlated with gender, tumor stage, lymph node stage, and distant metastasis stage. Finally, overexpression of SHMT2 promoted BLCA cell proliferation and suppressed apoptosis, the silencing of SHMT2 significantly inhibited BLCA cell proliferation by impairing the cell cycle, and promoting apoptosis. SHMT2 mediates BLCA cells growth by regulating STAT3 signaling. In summary, SHMT2 regulates the proliferation, cell cycle and apoptosis of BLCA cells, and may act as a candidate therapeutic target for BLCA.

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Prognostic Value of MUC2 Expression in Colorectal Cancer: A Systematic Review and Meta-Analysis

Gastroenterology Research and Practice ◽

10.1155/2018/6986870 ◽

2018 ◽

Vol 2018 ◽

pp. 1-12 ◽

Cited By ~ 5

Author(s):

Chao Li ◽

Didi Zuo ◽

Libin Yin ◽

Yuyang Lin ◽

Chenguang Li ◽

...

Keyword(s):

Colorectal Cancer ◽

Meta Analysis ◽

Disease Free Survival ◽

Expression Level ◽

Cochrane Library ◽

Depth Of Invasion ◽

Poor Prognostic Factor ◽

Free Survival ◽

Expression Levels ◽

Muc2 Expression

Background. The reliability of MUC2 as a prognostic marker in colorectal cancer (CRC) is controversial. This study evaluated the association between MUC2 expression levels in CRC tissues and prognosis. Methods. The PubMed, Web of Science, Embase, Cochrane Library, China Biology Medicine disc (CBMdisc), Wanfang Database, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies exploring the relationship between MUC2 expression in CRC tissues and overall survival (OS). Pooled hazard ratios (HRs) and risk ratios (RRs) with 95% confidence intervals (CIs) were used to evaluate the associations between MUC2 expression levels and prognosis and MUC2 expression levels and CRC clinicopathological characteristics, respectively. Results. The meta-analysis included 11 studies (2619 patients). Low MUC2 expression level was significantly associated with poor OS (HR, 1.67; 95% CI, 1.43–1.94; P<0.00001) and disease-free survival (DFS)/recurrence-free survival (RFS) (HR, 1.60; 95% CI, 1.21–2.12; P=0.001) in patients with CRC. Low MUC2 expression level was associated with advanced TNM stage (RR, 1.42; 95% CI, 1.26–1.60; P<0.00001), lymph node metastasis (RR, 1.41; 95% CI, 1.25–1.60; P<0.00001), lymphatic invasion (RR,1.64; 95% CI, 1.26–2.12; P=0.0002), rectal tumor site (RR, 1.26; 95% CI, 1.09–1.46; P=0.001), and large tumor size (RR,1.32; 95% CI, 1.02–1.70; P=0.03). There were no associations between low MUC2 expression level and gender, histological grade, depth of invasion, and distant metastasis. Conclusion. The low levels of MUC2 in CRC tissues are poor prognostic factor independent of stage or other well-recognized markers of later-stage disease. Large well-designed cohort studies are required to validate MUC2 as a biomarker for poor prognosis in CRC.

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Gene Alterations of N6-Methyladenosine (m6A) Regulators in Colorectal Cancer: A TCGA Database Study

BioMed Research International ◽

10.1155/2020/8826456 ◽

2020 ◽

Vol 2020 ◽

pp. 1-13

Author(s):

Qian Zhang ◽

Yuping Cai ◽

Vadim Kurbatov ◽

Sajid A. Khan ◽

Lingeng Lu ◽

...

Keyword(s):

Mrna Expression ◽

Messenger Rna ◽

Immune Cell ◽

Disease Free Survival ◽

Enrichment Analysis ◽

Gene Set Enrichment Analysis ◽

The Cancer Genome Atlas ◽

Cell Infiltration ◽

Immune Cell Infiltration ◽

The Relationship

N6-methyladenosine (m6A) plays an important role in many cancers. However, few studies have examined the role of m6A in colorectal CRC. To examine the effect of m6A on CRC, we studied the genome of 591 CRC cases from The Cancer Genome Atlas (TCGA). The relationship between the messenger RNA (mRNA) expression, copy number variation (CNVs), and mutations of m6A “Writers,” “Readers,” and “Erasers,” prognosis, immune cell infiltration, and genetic mutations in CRC cases were analyzed. CNVs and mutations were found in thirteen m6A regulators. As expected, gain and amplification of m6A regulators increased the mRNA expression of these regulators, while deletion led to reduction in the mRNA expression. Moreover, CNVs and mutation of these regulators were significantly associated with APC, TP53, and microsatellite instability (MSI) status ( p < 0.001 , p < 0.001 , and p = 0.029 , respectively). CNVs of m6A regulators also correlated with inferred immune cell infiltration in CRC tissues, especially in colon tissues. Additionally, alterations of RBM15, YTHDF2, YTHDC1, YTHDC2, and METTL14 genes were related to the worse overall survival and disease-free survival (DFS) of CRC patients. Specifically, the deletion status of “Writers” was also correlated to the DFS of CRC patients ( p = 0.02 ). Gene set enrichment analysis found that FTO was involved in mRNA 3 ′ end processing, polyubiquitin binding, and RNA polymerase promoter elongation, while YTHDC1 was related to interferon-alpha and gamma response. In conclusion, a novel relationship was identified between CNVs and mutations of m6A regulators with prognosis and inferred immune function of CRC. These findings will improve the understanding of the relationship of m6A in CRC.

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High lncSNHG15 expression may predict poor cancer prognosis: a meta-analysis based on the PRISMA and the bio-informatics analysis

Bioscience Reports ◽

10.1042/bsr20194468 ◽

2020 ◽

Vol 40 (7) ◽

Cited By ~ 1

Author(s):

Shi Xu Fang ◽

Cheng Chen ◽

Qiang Guo ◽

Xi Xian Ke ◽

Hong Ling Lu ◽

...

Keyword(s):

Histological Grade ◽

Meta Analysis ◽

Disease Free Survival ◽

Cancer Prognosis ◽

High Expression ◽

Expression Level ◽

Cochrane Library ◽

Multiple Cancer ◽

Cancer Types ◽

High Expression Level

Abstract Background: SNHG15 has been reported to be aberrantly expressed in various tumor tissues and could serve as a promising prognostic cancer biomarker. Previous studies on SNHG15 yielded inconsistent results with insufficient sampling. Here, a meta-analysis was conducted to investigate the prognostic value of SNHG15 in multiple cancers. Methods: Relevant studies were retrieved from six electronic databases including PubMed, Cochrane Library, Google Scholar, Embase, Web of Science and China National Knowledge Infrastructure (CNKI). Fifteen publications comprising 1318 patients were included. The publication bias was identified by the Begg’s Test, and the sensitivity analysis was also performed. Results: The results demonstrated a positive correlation between high expression level of lncSNHG15 and short overall survival (hazard ratio (HR) = 2.07, 95% confidence interval (CI), 1.48–2.88; P<0.0001) and disease-free survival (DFS) (HR = 2.32, 95% CI, 1.53–3.53; P<0.0001). The analysis based on different cancer types showed that SNHG15 had the most prominent prognostic potential in Glioma (HR = 3.81; 95% CI, 0.84–42.69; P=0.28). Moreover, the high expression level of lncSNHG15 indicated advanced TNM stage (OR = 2.52; 95% CI, 1.33–4.76; P=0.00001), lymph node metastasis (OR = 2.41, 95% CI, 0.99–4.81; P=0.05), bigger tumor size (OR = 2.06; 95% CI, 1.03–4.13; P=0.04) and poor histological grade (OR = 2.62, 95% CI, 1.90–3.59; P<0.00001), yet no association with distant metastasis (OR = 1.64, 95% CI, 0.40–6.74; P=0.49), age (OR = 0.98, 95% CI, 0.78–1.22; P=0.84) and gender (OR = 0.9, 95% CI, 0.71–1.14; P=0.3838) was found. Its conclusions further confirmed by exploring TCGA databases. Conclusion: It revealed that lncSNHG15 might be a promising prognostic biomarker of multiple cancer types, especially in Glioma.

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Prognostic significance of microRNA-135 in patients with digestive system cancers: a systematic review and meta-analysis

Bioscience Reports ◽

10.1042/bsr20190845 ◽

2019 ◽

Vol 39 (12) ◽

Author(s):

Ce Chao ◽

Chen Sang ◽

Min Wang ◽

Zijin Wang ◽

Yanfei Li ◽

...

Keyword(s):

Prognostic Value ◽

Large Scale ◽

Digestive System ◽

Meta Analysis ◽

Prognostic Significance ◽

Disease Free Survival ◽

The Cancer Genome Atlas ◽

Cochrane Library ◽

Free Survival ◽

Non Coding Rna

Abstract Background: MicroRNA-135 (miR-135) is a well-known non-coding RNA that has been demonstrated to participate in tumorigenesis and cancer development; however, the clinical prognostic value of miR-135 in digestive system cancers remains controversial. This meta-analysis aims to explore the potential value of miR-135 as a prognostic marker for digestive system cancers. Methods: The PubMed, Embase, Cochrane Library, and Web of Science databases were searched for eligible articles published before 31 August 2019. Stata 12.0 software was used to analyze the overall survival (OS), disease-free survival (DFS), and recurrence-free survival (RFS) rates to access the prognostic value of miR-135 in digestive system cancers. We then used The Cancer Genome Atlas (TCGA) datasets to validate the meta-analysis results. Results A total of 1470 patients from 17 studies were included in this meta-analysis. The pooled results showed that enhanced miR-135 expression was significantly associated with poor OR (hazard ratio (HR): 1.790; 95% confidence interval (95% CI): 1.577–2.031; P=0.000), DFS (HR: 1.482; 95% CI: 0.914–2.403; P=0.110), and RFS (HR: 3.994; 95% CI: 1.363–11.697; P=0.012) in digestive system cancers. A sensitivity analysis confirmed the reliability of our findings, and no significant publication bias was observed. Conclusion: MiR-135 can be used as a novel biomarker for patients with digestive system cancers. We look forward to future large-scale clinical studies that will investigate the prognostic value of miR-135.

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