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Systems biomarkers for papillary thyroid cancer prognosis and treatment through multi-omics networks.
Gulfidan, G, Soylu, M, Demirel, D, Erdonmez, HBC, Beklen, H, Ozbek Sarica, P, Arga, KY, Turanli, B
Archives of biochemistry and biophysics. 2022;:109085
Abstract
The identification of biomolecules associated with papillary thyroid cancer (PTC) has upmost importance for the elucidation of the disease mechanism and the development of effective diagnostic and treatment strategies. Despite particular findings in this regard, a holistic analysis encompassing molecular data from different biological levels has been lacking. In the present study, a meta-analysis of four transcriptome datasets was performed to identify gene expression signatures in PTC, and reporter molecules were determined by mapping gene expression data onto three major cellular networks, i.e., transcriptional regulatory, protein-protein interaction, and metabolic networks. We identified 282 common genes that were differentially expressed in all PTC datasets. In addition, six proteins (FYN, JUN, LYN, PML, SIN3A, and RARA), two Erb-B2 receptors (ERBB2 and ERBB4), two cyclin-dependent receptors (CDK1 and CDK2), and three histone deacetylase receptors (HDAC1, HDAC2, and HDAC3) came into prominence as proteomic signatures in addition to several metabolites including lactaldehyde and proline at the metabolome level. Significant associations with calcium and MAPK signaling pathways and transcriptional and post-transcriptional activities of 12 TFs and 110 miRNAs were also observed at the regulatory level. Among them, six miRNAs (miR-30b-3p, miR-15b-5p, let-7a-5p, miR-130b-3p, miR-424-5p, and miR-193b-3p) were associated with PTC for the first time in the literature, and the expression levels of miR-30b-3p, miR-15b-5p, and let-7a-5p were found to be predictive of disease prognosis. Drug repositioning and molecular docking simulations revealed that 5 drugs (prochlorperazine, meclizine, rottlerin, cephaeline, and tretinoin) may be useful in the treatment of PTC. Consequently, we report here biomolecule candidates that may be considered as prognostic biomarkers or potential therapeutic targets for further experimental and clinical trials for PTC.
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2.
Prognostic Value of NOX4 Expression in Cancer Patients: A Systematic Review and Meta-analysis.
Koh, HM, Jang, BG, Hyun, CL, Kim, DC
Disease markers. 2022;:8567642
Abstract
BACKGROUND Recent studies have shown that nicotinamide adenosine dinucleotide phosphate oxidase 4 (NOX4) is related to cancer development, proliferation, invasion, epithelial-to-mesenchymal transition, and metastasis. The prognostic value of NOX4 expression although has been reported in various cancers, it remains unclear as several studies have reported conflicting results. Therefore, the purpose of this study was to systematically investigate the prognostic value of NOX4 expression in cancer patients. METHOD Appropriate studies were collected by searching the PubMed, EMBASE, and Cochrane library databases, and the prognostic value of NOX4 expression in cancer patients was assessed through a meta-analysis. RESULTS Nine eligible studies involving 2675 cancer patients were included in this meta-analysis. We found that NOX4 expression is related to prognosis in cancer patients. In particular, high expression of NOX4 was significantly associated with overall survival in patients with gastrointestinal cancer (hazard ratio [HR]: 1.83, 95% confidence interval [CI]: 1.39-2.42, p < 0.001). CONCLUSION NOX4 expression is significantly correlated with overall survival in patients with gastrointestinal cancer, indicating that it could be a potential prognostic marker.
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3.
Urinary Angiogenin as a Marker for Bladder Cancer: A Meta-Analysis.
Aalami, AH, Abdeahad, H, Mesgari, M, Sathyapalan, T, Sahebkar, A
BioMed research international. 2021;:5557309
Abstract
AIMS: Bladder cancer (BCa) is a common cancer in North America and Europe that carries considerable morbidity and mortality. A reliable biomarker for early detection of the bladder is crucial for improving the prognosis of BCA. In this meta-analysis, we examine the diagnostic role of the angiogenin (ANG) protein in patients' urine with bladder neoplasm. METHODS We performed a systematic literature search using ScienceDirect, Web of Science, PubMed/MEDLINE, Scopus, Google Scholar, and Embase, up to 10th October 2020 databases. Meta-Disc V.1.4 and Comprehensive Meta-Analysis V.2.2 software calculated the pooled specificity, sensitivity, area under the curve (AUC), diagnostic odds ratio (DOR), positive likelihood ratio (LR+), negative likelihood ratio (LR-), Q ∗ index, and summary receiver-operating characteristic (SROC) for the role of ANG as a urinary biomarker for BCa patients. RESULTS Four case-control studies were included with 656 participants (417 cases and 239 controls) in this meta-analysis. The pooled sensitivity of 0.71 (95% CI: 0.66-0.75), specificity of 0.78 (95% CI: 0.73-0.81), LR+ of 3.34 (95% CI: 2.02-5.53), LR- of 0.37 (95% CI: 0.32-0.44), DOR of 9.99 (95% CI: 4.69-21.28), and AUC of 0.789 and Q ∗ index of 0.726 demonstrate acceptable diagnostic precision of ANG in identifying BCa. CONCLUSION This meta-analysis showed that ANG could be a fair biomarker for the diagnosis of BCa patients.
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Meta-analysis of the prognostic and clinical value of serum 25-hydroxyvitamin D levels in previously untreated lymphoma.
Tao, Y, Chen, H, Zhou, Y, Shi, Y
Future oncology (London, England). 2021;(14):1825-1838
Abstract
Background: This meta-analysis explored the prognostic and clinical value of serum 25-hydroxyvitamin D, 25(OH)D, levels in previously untreated lymphoma. Materials & methods: PubMed, Web of Science, Embase and the Cochrane Central Register of Controlled Trials databases were searched for eligible studies. Summary effect estimates and 95% CIs were pooled using random-effects or fixed-effects models. Results: Twelve studies with 4139 patients were included. Low level of serum 25(OH)D was associated with inferior progression-free survival (hazard ratio [HR]: 2.06; 95% CI: 1.82-2.32) and overall survival (HR: 1.94; 95% CI: 1.71-2.19), advanced disease (odds ratio [OR]: 1.52; 95% CI: 1.09-2.13) and elevated lactate dehydrogenase (OR: 1.84; 95% CI: 1.08-3.15). Conclusions: Low level of serum 25(OH)D is a prognostic risk factor for newly diagnosed lymphoma.
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Prognostic value of aldo-keto reductase family 1 member B10 (AKR1B10) in digestive system cancers: A meta-analysis.
Liu, R, Zheng, S, Yang, CY, Yu, Y, Peng, S, Ge, Q, Lin, Q, Li, Q, Shi, W, Shao, Y
Medicine. 2021;(14):e25454
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Abstract
BACKGROUND Numbers of studies have reported that the expression of aldo-keto reductase family 1 member B10 (AKR1B10) is abnormal in digestive system cancers, and could be used as a prognostic biomarker. However, the results are argued. Therefore, we conduct a meta-analysis to comprehensively evaluate the prognostic value of high AKR1B10 expression for overall survival (OS), disease specific survival (DSS), and disease-free survival/recurrence-free survival (DFS/PFS) in digestive system cancers. METHODS Hazard ratios (HRs) with its 95% confidence intervals (CIs) were calculated to assess the prognostic value of AKR1B10 by using the random effects model. The STATA version 12.0 software were used to perform all the analyses. RESULTS Eleven articles including 1428 patients involved in this meta-analysis. The pooled analysis suggested that high AKR1B10 expression was not associated with OS (HR: 1.18; 95% CI: 0.69-2.00) and DFS/PFS (HR: 1.08, 95% CI: 0.67-1.76) in digestive system cancers. However, Further analysis revealed that high AKR1B10 expression indicated poor OS in oral squamous cell carcinomas (OSCC) (HR: 2.92, 95% CI: 1.86-4.58) and favorable DSS in hepatocellular carcinoma (HCC) (HR: 0.71, 95% CI: 0.52-0.97). CONCLUSIONS The prognostic value of high AKR1B10 expression varied in different types of digestive system cancers. Further studies exploring the prognostic role of AKR1B10 in digestive system cancers are needed.
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Clinicopathological and prognostic value of S100A4 expression in non-small cell lung cancer: a meta-analysis.
Zhang, J, Gu, Y, Liu, X, Rao, X, Huang, G, Ouyang, Y
Bioscience reports. 2020;(7)
Abstract
BACKGROUND Numerous published studies have shown that S100A4 is frequently overexpressed in various human cancers. However, the association between S100A4 expression and prognosis or clinicopathological parameters in non-small cell lung cancer (NSCLC) remains unclear. Therefore, a meta-analysis was performed to identify the significance of S100A4 in NSCLC. METHODS Systematic literature search was conducted using PubMed, Embase, Web of Science, the Cochrane Library, the Chinese National Knowledge Infrastructure database (CNKI), and the Wanfang database to obtain relevant articles. A combined hazard ratio (HR) and its corresponding 95% confidence interval (CI) were used to evaluate the association between S100A4 expression and prognosis in NSCLC patients. Pooled odds ratio (OR) and 95% CI were calculated to assess the association between S100A4 expression and clinicopathological features in NSCLC. RESULTS NSCLC patients with overexpression of S100A4 had a worse prognosis than patients with low expression of S100A4 (HR = 1.77, 95% CI: 1.55-2.02, P<0.001). Additionally, overexpression of S100A4 was significantly correlated to patients' age (OR = 0.67, 95% CI: 0.49-0.91, P=0.010), tumor differentiation (OR = 2.20, 95% CI: 1.69-2.85, P<0.001), lymph node metastasis (LNM) (OR = 3.70, 95% CI: 2.25-6.06, P<0.001), Tumor-Node-Metastasis (TNM) stage (OR = 3.08, 95% CI: 2.10-4.53, P<0.001), and pathological subtype (OR = 1.77, 95% CI: 1.09-2.88, P=0.020). However, there was no association between S100A4 expression and other clinicopathological features in NSCLC, including gender, tumor size, and smoking. CONCLUSION S100A4 overexpression was associated with tumor progression and poor prognosis in NSCLC patients. Hence, S100A4 might serve as a potential prognostic biomarker in NSCLC.
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Serum Folate Levels and Lung Cancer Risk: A Meta- Epidemiological Study of Population-based Case-Control Studies.
Bae, JM
Asian Pacific journal of cancer prevention : APJCP. 2020;(6):1829-1833
Abstract
OBJECTIVE While it has been claimed that lung cancer occurs due to epigenetic mechanisms, four systematic reviews were reported to investigate the association between serum folate levels and lung cancer risk. Considering some methodological problems founded in the systematic review, a meta-epidemiological study was conducted. METHODS The selection criteria of this study were defined that a case-control study was conducted to determine the risk of lung cancer occurrence according to the concentration of serum folate and its results showed odds ratio and its 95% confidence interval. Additional paper was explored from cited lists of 4 papers selected by previous systematic reviews. Random effect model was applied if I-squared value was over 50%. RESULTS For 5 case-control studies selected, the summary odds ratios (and their 95% confidence intervals) were 0.82 (0.74-0.90) in men, 0.70 (0.62-0.79) in former smokers, and 0.86 (0.75-1.00) in non-smokers. CONCLUSION Higher foliate levels can decrease lung cancer risk in men and former smokers. Especially, the protective effect was highest in former smokers compared in non-smokers and current smokers. Based on these facts, folate fortification programs to reduce lung cancer risk would be focused on former smokers in men. And some epidemiological studies are needed to provide a hypothesis to explain the sex differences in the association between folate and lung cancer risk.
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A systematic review and meta-analysis of higher expression of folate receptor alpha (FOLR1) predicts poor cancer prognosis.
Liu, Y, Lian, T, Yao, Y
Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals. 2020;(5):367-374
Abstract
Folate receptor alpha (FOLR1), a glycosylphosphatidylinositol-linked protein, is a well characterized folate transporter. However, the prognostic power of FOLR1 in cancer remains controversial. We conducted a meta-analysis to assess the prognostic roles of FOLR1 on different cancers. Twelve studies involving 4471 patients were included in this meta-analysis. The pooled analysis indicated that high FOLR1 significantly predicted poor overall survival (OS) (pooled hazard ratio (HR) = 0.78, 95% confidence interval (CI) = 0.64-0.94, p = 0.009) and the disease-free survival (DFS) (HR = 1.25, 95% CI = 1.07-1.47, p = 0.005). Subgroup analyses based on tumour type found that high FOLR1 level was associated with poor OS in breast cancer (HR = 2.66, 95% CI = 1.54-4.59, p = 0.0005) and endometrial carcinoma (HR = 1.30, 95% CI = 1.05-1.61, p = 0.02). However, FOLR1 has relatively weakly correlation with gender, tumour size and chemotherapy. Additionally, overexpression of FOLR1 was correlated with grade, FIGO stage, vital status and nodule status. The present meta-analysis indicated that the high expression of FOLR1 is associated with the poor survival of cancer patients, which is helpful for the clinical decision-making process.
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Prognostic and clinicopathological significance of SR-B1 in solid tumors: A meta-analysis.
Wang, M, Chao, C, Luo, G, Wang, B, Zhan, X, Di, D, Qian, Y, Zhang, X
Pathology, research and practice. 2020;(4):152849
Abstract
BACKGROUND The expression of cell surface receptors is abnormal in malignant tumors. The scavenger receptor class B type I (SR-B1) is an integral membrane glycoprotein receptor that facilitates the selective uptake of cholesterol by malignant cells. Accumulated studies investigated the prognostic role of SR-B1 in many solid tumors, such as breast cancer, lung cancer and so on. However, the conclusions remain undefined. Therefore, we conducted this meta-analysis to obtain more accurate evaluation of prognostic significance of SR-B1 in solid tumors. MATERIALS AND METHODS We searched PubMed, Embase, Web of science and Cochrane library for eligible studies published before November 2018. The included studies investigated the association between the SR-B1 level and clinicopathological features including survival outcomes in solid tumors. Hazard ratios (HRs) with 95% confidence intervals (CIs) were adopted to assess the survival outcomes and odds ratio (ORs) with 95% confidence intervals (CIs) were pooled to evaluated the clinicopathological features. RESULTS A total of 10 studies involving 2585 patients were included in this meta-analysis. The results showed that low SR-B1 level was significantly correlated with earlier tumor grade (pooled OR = 2.09, 95%CI = 1.28-3.43, P = 0.001), less nodal involvement (pooled OR = 2.07, 95%CI = 1.43-3.0, P < 0.001), less distant metastasis (OR = 19.8, 95%CI = 2.58-151.65, P = 0.004), smaller tumor size (OR = 2.34, 95%CI = 1.53-3.57, P < 0.001), earlier TNM stage (OR = 3.77, 95%CI = 1.67-8.48, P = 0.001), lower recurrence (HR = 1.98, 95%CI = 1.57-2.49, P = 0.000), and better OS (HR = 1.99, 95%CI = 1.70-2.31, P = 0.000). CONCLUSION The low expression of SR-B1 was significantly associated with better clinicopathological status and longer survival in patients with solid tumors. SR-B1 might act as a promising prognostic biomarker for solid tumors.
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FOLFOX treatment response prediction in metastatic or recurrent colorectal cancer patients via machine learning algorithms.
Lu, W, Fu, D, Kong, X, Huang, Z, Hwang, M, Zhu, Y, Chen, L, Jiang, K, Li, X, Wu, Y, et al
Cancer medicine. 2020;(4):1419-1429
Abstract
Early identification of metastatic or recurrent colorectal cancer (CRC) patients who will be sensitive to FOLFOX (5-FU, leucovorin and oxaliplatin) therapy is very important. We performed microarray meta-analysis to identify differentially expressed genes (DEGs) between FOLFOX responders and nonresponders in metastatic or recurrent CRC patients, and found that the expression levels of WASHC4, HELZ, ERN1, RPS6KB1, and APPBP2 were downregulated, while the expression levels of IRF7, EML3, LYPLA2, DRAP1, RNH1, PKP3, TSPAN17, LSS, MLKL, PPP1R7, GCDH, C19ORF24, and CCDC124 were upregulated in FOLFOX responders compared with nonresponders. Subsequent functional annotation showed that DEGs were significantly enriched in autophagy, ErbB signaling pathway, mitophagy, endocytosis, FoxO signaling pathway, apoptosis, and antifolate resistance pathways. Based on those candidate genes, several machine learning algorithms were applied to the training set, then performances of models were assessed via the cross validation method. Candidate models with the best tuning parameters were applied to the test set and the final model showed satisfactory performance. In addition, we also reported that MLKL and CCDC124 gene expression were independent prognostic factors for metastatic CRC patients undergoing FOLFOX therapy.