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World Journal of Surgical Oncology Feb 2015Screening programmes exist in many countries for colorectal cancer. In recent years, there has been a drive for a non-invasive screening marker of higher sensitivity and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Screening programmes exist in many countries for colorectal cancer. In recent years, there has been a drive for a non-invasive screening marker of higher sensitivity and specificity. Stool-based pyruvate kinase isoenzyme M2 (M2-PK) is one such biomarker under investigation. The aim of this systematic review and meta-analysis is to determine the diagnostic accuracy, sensitivity and specificity of M2-PK as a screening tool in colorectal cancer.
METHODS
A literature search of Ovid Medline, EMBASE and Google Scholar was carried out. The search strategy was restricted to human subjects and studies published in English. Data on sensitivity and specificity were extracted and pooled. Statistical analysis was conducted using summary receiver operating characteristic (SROC) curve methodology.
RESULTS
A total of eight studies were suitable for data synthesis and analysis. Our analysis showed a pooled sensitivity and specificity for M2-PK to be 79% (CI 73%-83%) and 80% (CI 73%-86%), respectively. The accuracy of M2-PK was 0.85(0.82-0.88).
CONCLUSION
Faecal M2-PK assay has a relatively good sensitivity and specificity and high accuracy for screening colorectal cancer.
Topics: Biological Assay; Case-Control Studies; Colorectal Neoplasms; Early Detection of Cancer; Humans; Prognosis; Pyruvate Kinase
PubMed: 25888768
DOI: 10.1186/s12957-015-0446-4 -
European Journal of Haematology Aug 2020Pyruvate kinase deficiency (PK deficiency) is a rare disorder caused by compound heterozygosity or homozygosity for > 300 mutations in the PKLR gene. To understand PK... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Pyruvate kinase deficiency (PK deficiency) is a rare disorder caused by compound heterozygosity or homozygosity for > 300 mutations in the PKLR gene. To understand PK deficiency prevalence, we conducted a systematic literature review.
METHODS
We queried Embase and Medline for peer-reviewed references reporting PK deficiency prevalence/incidence, PKLR mutant allele frequency (MAF) among the general population, or crude results from which these metrics could be derived.
RESULTS
Of 1390 references screened, 1296 were excluded after title/abstract review; 60 were excluded after full-text review. Four of the remaining 34 studies were considered high-quality for estimating PK deficiency prevalence. Two high-quality studies identified cases from source populations of known sizes, producing estimates of diagnosed PK deficiency prevalence of 3.2 and 8.5 per million. Another high-quality study derived an estimate of diagnosed PK deficiency prevalence of 6.5 per million by screening jaundiced newborns. The final high-quality study estimated total diagnosed and undiagnosed PK deficiency prevalence to be 51 per million through extrapolation from observed MAFs.
CONCLUSIONS
We conclude that prevalence of clinically diagnosed PK deficiency is likely between 3.2 and 8.5 per million in Western populations, while the prevalence of diagnosed and undiagnosed PK deficiency could possibly be as high as 51 per million.
Topics: Alleles; Anemia, Hemolytic, Congenital Nonspherocytic; Gene Frequency; Genetic Predisposition to Disease; Genotype; Humans; Mutation; Population Surveillance; Prevalence; Pyruvate Kinase; Pyruvate Metabolism, Inborn Errors
PubMed: 32279356
DOI: 10.1111/ejh.13424 -
International Journal of Cancer Oct 2012The measurement of fecal tumor M2-pyruvate kinase (PKM2), overexpressed in tumor cells, has been proposed as a novel tool for detecting colorectal cancer (CRC). However,... (Meta-Analysis)
Meta-Analysis
The measurement of fecal tumor M2-pyruvate kinase (PKM2), overexpressed in tumor cells, has been proposed as a novel tool for detecting colorectal cancer (CRC). However, the sensitivity and specificity of this test varied among studies. The aim of this meta-analysis was to determine the diagnostic accuracy of fecal PKM2 for CRC and to evaluate its utility in the CRC screening. It was compared to guaiac fecal occult blood test (gFOBT) or immunological fecal occult blood test (iFOBT). Through comprehensive literature search, 10 studies met the inclusion criteria and were included. Summary estimates for sensitivity and specificity were calculated by using the bivariate random effect model. The hierarchical summary receiver operating characteristic curve was also undertaken. The overall sensitivity and specificity of fecal PKM2 for detecting CRC were 79% (95% CI = 75-83%) and 81% (95% CI = 73-87%), respectively. The summary positive predictive value and negative predictive value were 74% (95% CI = 56-87%) and 86% (95% CI = 79-91%), respectively. The pooled diagnostic odds ratio was 16 (95% CI = 10-26). In head-to-head comparison, the diagnostic odds ratio of PKM2 and gFOBT for CRC were 10.167 (95% CI = 5.992-17.250) and 6.557 (95% CI = 3.467-12.403), respectively. The diagnostic odds ratio of PKM2 and iFOBT for CRC were 9.542 (95% CI = 5.893-15.452) and 67.248 (95% CI = 16.194-279.26), respectively. The fecal PKM2 test was a diagnostic tool with moderate sensitivity and specificity for detecting CRC. Its diagnostic efficiency was similar to that of gFOBT. Because of its relatively low specificity and positive predict value, fecal PKM2 was not recommended used alone as a screening tool for CRC.
Topics: Colorectal Neoplasms; Diagnostic Tests, Routine; Early Detection of Cancer; Humans; Occult Blood; Pyruvate Kinase; ROC Curve; Review Literature as Topic
PubMed: 22261915
DOI: 10.1002/ijc.27442 -
Chinese Journal of Cancer Aug 2017Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy, with a high incidence and poor prognosis. In the past several decades, hundreds of proteins have... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is an aggressive malignancy, with a high incidence and poor prognosis. In the past several decades, hundreds of proteins have been reported to be associated with the prognosis of ESCC, but none has been widely accepted to guide clinical care. This study aimed to identify proteins with great potential for predicting prognosis of ESCC.
METHODS
We conducted a systematic review on immunohistochemical (IHC) prognostic markers of ESCC according to the 2009 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Guidelines. Literature related to IHC prognostic markers of ESCC were searched from PubMed, Embase, Web of Science, and Cochrane Library until January 30th, 2017. The risk of bias of these original studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool.
RESULTS
We identified 11 emerging IHC markers with reproducible results, including eight markers [epidermal growth factor receptor (EGFR), Cyclin D1, vascular endothelial growth factor (VEGF), Survivin, Podoplanin, Fascin, phosphorylated mammalian target of rapamycin (p-mTOR), and pyruvate kinase M2 (PKM2)] indicating unfavorable prognosis and 3 markers (P27, P16, and E-cadherin) indicating favorable prognosis of ESCC.
CONCLUSION
Strong evidence supports that these 11 emerging IHC markers or their combinations may be useful in predicting prognosis and aiding personalized therapy decision-making for ESCC patients.
Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Female; Humans; Male; Neoplasm Proteins; Prognosis
PubMed: 28818096
DOI: 10.1186/s40880-017-0232-5 -
Journal of Gastrointestinal and Liver... Mar 2018Growing evidence has shown that M2-PK is involved in cancer diagnosis and prognosis. The overall diagnostic accuracy of the pyruvate kinase isoenzyme type M2 (M2-PK) in... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Growing evidence has shown that M2-PK is involved in cancer diagnosis and prognosis. The overall diagnostic accuracy of the pyruvate kinase isoenzyme type M2 (M2-PK) in biliary tract carcinoma (BTC) remains controversial. We performed a meta-analysis to evaluate the diagnostic value of M2-PK for BTC.
METHODS
The online PubMed, Cochrane, Web of Science, and Embase databases were searched for eligible studies published until August 8th, 2017. The Quality Assessment for Diagnostic Accuracy Studies 2 (QUADAS-2) was used to evaluate study quality. All statistical analyses were conducted with Stata 12.0.
RESULTS
We included 7 studies from 5 articles with 410 patients with BTC and 438 controls. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and AUC for M2-PK in the diagnosis of BTC were 0.79 (95%CI 0.70-0.86), 0.81 (95%CI 0.71-0.88), 4.1 (95%CI 2.5-6.8), 0.26 (95%CI 0.16-0.41), 17.159 (95%CI 5.468-54.071), and 0.87 (95%CI 0.83-0.89), respectively. The same indicators assessed for CA19-9 were as follows: 0.70 (95%CI 0.62-0.77), 0.71 (95%CI 0.45-0.87), 2.38 (95%CI 1.2-4.73), 0.43 (95%CI 0.34-0.53), 6.28 (95%CI 2.4-16.44) and 0.73 (95%CI 0.69-0.77), respectively. Additionally, the diagnostic value of M2-PK varied based on characteristics of golden methods and different cut-off values.
CONCLUSIONS
This meta-analysis showed that M2-PK had a better diagnostic accuracy for BTC compared with CA19-9, with moderate diagnostic performance. However, prospective studies are required to confirm its diagnostic value.
Topics: Bile; Biliary Tract Neoplasms; Biomarkers, Tumor; CA-19-9 Antigen; Cholangiocarcinoma; Humans; Pyruvate Kinase
PubMed: 29557418
DOI: 10.15403/jgld.2014.1121.271.wqw -
Neurobiology of Disease May 2024Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial... (Review)
Review
Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting 1 in 36 children and is associated with physiological abnormalities, most notably mitochondrial dysfunction, at least in a subset of individuals. This systematic review and meta-analysis discovered 204 relevant articles which evaluated biomarkers of mitochondrial dysfunction in ASD individuals. Significant elevations (all p < 0.01) in the prevalence of lactate (17%), pyruvate (41%), alanine (15%) and creatine kinase (9%) were found in ASD. Individuals with ASD had significant differences (all p < 0.01) with moderate to large effect sizes (Cohen's d' ≥ 0.6) compared to controls in mean pyruvate, lactate-to-pyruvate ratio, ATP, and creatine kinase. Some studies found abnormal TCA cycle metabolites associated with ASD. Thirteen controlled studies reported mitochondrial DNA (mtDNA) deletions or variations in the ASD group in blood, peripheral blood mononuclear cells, lymphocytes, leucocytes, granulocytes, and brain. Meta-analyses discovered significant differences (p < 0.01) in copy number of mtDNA overall and in ND1, ND4 and CytB genes. Four studies linked specific mtDNA haplogroups to ASD. A series of studies found a subgroup of ASD with elevated mitochondrial respiration which was associated with increased sensitivity of the mitochondria to physiological stressors and neurodevelopmental regression. Lactate, pyruvate, lactate-to-pyruvate ratio, carnitine, and acyl-carnitines were associated with clinical features such as delays in language, social interaction, cognition, motor skills, and with repetitive behaviors and gastrointestinal symptoms, although not all studies found an association. Lactate, carnitine, acyl-carnitines, ATP, CoQ10, as well as mtDNA variants, heteroplasmy, haplogroups and copy number were associated with ASD severity. Variability was found across biomarker studies primarily due to differences in collection and processing techniques as well as the intrinsic heterogeneity of the ASD population. Several studies reported alterations in mitochondrial metabolism in mothers of children with ASD and in neonates who develop ASD. Treatments targeting mitochondria, particularly carnitine and ubiquinol, appear beneficial in ASD. The link between mitochondrial dysfunction in ASD and common physiological abnormalities in individuals with ASD including gastrointestinal disorders, oxidative stress, and immune dysfunction is outlined. Several subtypes of mitochondrial dysfunction in ASD are discussed, including one related to neurodevelopmental regression, another related to alterations in microbiome metabolites, and another related to elevations in acyl-carnitines. Mechanisms linking abnormal mitochondrial function with alterations in prenatal brain development and postnatal brain function are outlined. Given the multisystem complexity of some individuals with ASD, this review presents evidence for the mitochondria being central to ASD by contributing to abnormalities in brain development, cognition, and comorbidities such as immune and gastrointestinal dysfunction as well as neurodevelopmental regression. A diagnostic approach to identify mitochondrial dysfunction in ASD is outlined. From this evidence, it is clear that many individuals with ASD have alterations in mitochondrial function which may need to be addressed in order to achieve optimal clinical outcomes. The fact that alterations in mitochondrial metabolism may be found during pregnancy and early in the life of individuals who eventually develop ASD provides promise for early life predictive biomarkers of ASD. Further studies may improve the understanding of the role of the mitochondria in ASD by better defining subgroups and understanding the molecular mechanisms driving some of the unique changes found in mitochondrial function in those with ASD.
PubMed: 38703861
DOI: 10.1016/j.nbd.2024.106520 -
Advances in Therapy Jun 2021Lower gastrointestinal (GI) cancers are a major cause of cancer deaths worldwide. Prognosis improves with earlier diagnosis, and non-invasive biomarkers have the... (Meta-Analysis)
Meta-Analysis
Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Lower Gastrointestinal Cancers: A Systematic Review and Meta-Analysis.
INTRODUCTION
Lower gastrointestinal (GI) cancers are a major cause of cancer deaths worldwide. Prognosis improves with earlier diagnosis, and non-invasive biomarkers have the potential to aid with early detection. Substantial investment has been made into the development of biomarkers; however, studies are often carried out in specialist settings and few have been evaluated for low-prevalence populations.
METHODS
We aimed to identify novel biomarkers for the detection of lower GI cancers that have the potential to be evaluated for use in primary care. MEDLINE, Embase, Emcare and Web of Science were systematically searched for studies published in English from January 2000 to October 2019. Reference lists of included studies were also assessed. Studies had to report on measures of diagnostic performance for biomarkers (single or in panels) used to detect colorectal or anal cancers. We included all designs and excluded studies with fewer than 50 cases/controls. Data were extracted from published studies on types of biomarkers, populations and outcomes. Narrative synthesis was used, and measures of specificity and sensitivity were meta-analysed where possible.
RESULTS
We identified 142 studies reporting on biomarkers for lower GI cancers, for 24,844 cases and 45,374 controls. A total of 378 unique biomarkers were identified. Heterogeneity of study design, population type and sample source precluded meta-analysis for all markers except methylated septin 9 (mSEPT9) and pyruvate kinase type tumour M2 (TuM2-PK). The estimated sensitivity and specificity of mSEPT9 was 80.6% (95% CI 76.6-84.0%) and 88.0% (95% CI 79.1-93.4%) respectively; TuM2-PK had an estimated sensitivity of 81.6% (95% CI 75.2-86.6%) and specificity of 80.1% (95% CI 76.7-83.0%).
CONCLUSION
Two novel biomarkers (mSEPT9 and TuM2-PK) were identified from the literature with potential for use in lower-prevalence populations. Further research is needed to validate these biomarkers in primary care for screening and assessment of symptomatic patients.
Topics: Biomarkers; Early Detection of Cancer; Gastrointestinal Neoplasms; Humans; Prevalence; Sensitivity and Specificity
PubMed: 33907946
DOI: 10.1007/s12325-021-01645-6 -
Scientific Reports Feb 2022Early diagnosis of colorectal advanced neoplasms (ANs), including colorectal cancer (CRC) and advanced adenoma (AA), has a positive effect on the survival rate. As a... (Comparative Study)
Comparative Study Meta-Analysis
Early diagnosis of colorectal advanced neoplasms (ANs), including colorectal cancer (CRC) and advanced adenoma (AA), has a positive effect on the survival rate. As a first attempt, the aim of this meta-analysis was to compare the diagnostic accuracy of faecal protein biomarkers for the detection of colorectal neoplasms with consideration of a wide range of covariates. A systematic literature search was performed up to Jun 10, 2021 on Web of Sciences, Scopus and PubMed. The diagnostic accuracies were calculated using the bivariate/hierarchical random effect model. Biomarkers were determined to be clinically applicable (CA) if they had areas under the curve > 0.70 and positive and negative likelihood ratios > 2 and < 0.5, respectively. A total of 47,059 test results were extracted from 16 immunochemical faecal occult blood test (iFOBT), 26 pyruvate kinase-M2 (PK-M2) and 23 faecal calprotectin (FC) studies. Only iFOBT, PK-M2 and FC for CRC plus iFOBT and PK-M2 for AN were CA. iFOBT had significantly superior accuracy (P = 0.02 versus PK-M2 and P < 0.01 versus FC for CRC; P < 0.01 versus PK-M2 for AN). Regarding covariates, the lateral flow method of PK-M2 measurement increased its accuracy for CRC detection compared to the enzyme-linked immunosorbent assay (P < 0.01). iFOBT is recommended as the most accurate faecal biomarker for CRC and AN diagnosis.
Topics: Adenoma; Adult; Aged; Biomarkers; Biomarkers, Tumor; Colorectal Neoplasms; Early Detection of Cancer; Enzyme-Linked Immunosorbent Assay; Feces; Female; Humans; Leukocyte L1 Antigen Complex; Male; Middle Aged; Occult Blood; Pyruvate Kinase; Sensitivity and Specificity
PubMed: 35173276
DOI: 10.1038/s41598-022-06689-4 -
German Medical Science : GMS E-journal 2023Stool DNA testing for early detection of colorectal cancer (CRC) is a non-invasive technology with the potential to supplement established CRC screening tests. The aim...
BACKGROUND
Stool DNA testing for early detection of colorectal cancer (CRC) is a non-invasive technology with the potential to supplement established CRC screening tests. The aim of this health technology assessment was to evaluate effectiveness and safety of currently CE-marked stool DNA tests, compared to other CRC tests in CRC screening strategies in an asymptomatic screening population.
METHODS
The assessment was carried out following the guidelines of the European Network for Health Technology Assessment (EUnetHTA). This included a systematic literature search in MED-LINE, Cochrane and EMBASE in 2018. Manufacturers were asked to provide additional data. Five patient interviews helped assessing potential ethical or social aspects and patients' experiences and preferences. We assessed the risk of bias using QUADAS-2, and the quality of the body of evidence using GRADE.
RESULTS
We identified three test accuracy studies, two of which investigated a multitarget stool DNA test (Cologuard, compared fecal immunochemical test (FIT)) and one a combined DNA stool assay (ColoAlert, compared to guaiac-based fecal occult blood test (gFOBT), Pyruvate Kinase Isoenzyme Type M2 (M2-PK) and combined gFOBT/M2-PK). We found five published surveys on patient satisfaction. No primary study investigating screening effects on CRC incidence or on overall mortality was found. Both stool DNA tests showed in direct comparison higher sensitivity for the detection of CRC and (advanced) adenoma compared to FIT, or gFOBT, respectively, but had lower specificity. However, these comparative results may depend on the exact type of FIT used. The reported test failure rates were higher for stool DNA testing than for FIT. The certainty of evidence was moderate to high for Cologuard studies, and low to very low for the ColoAlert study which refers to a former version of the product and yielded no direct evidence on the test accuracy for ad-vanced versus non-advanced adenoma.
CONCLUSIONS
ColoAlert is the only stool DNA test currently sold in Europe and is available at a lower price than Cologuard, but reliable evidence is lacking. A screening study including the current product version of ColoAlert and suitable comparators would, therefore, help evaluate the effectiveness of this screening option in a European context.
Topics: Humans; Adenoma; Colorectal Neoplasms; DNA, Neoplasm; Early Detection of Cancer; Guaiac; Mass Screening; Occult Blood; Technology Assessment, Biomedical
PubMed: 37426885
DOI: 10.3205/000320 -
Cellular Physiology and Biochemistry :... Apr 2021Yes-associated protein (YAP) is one of the Hippo pathway's two effectors, a pathway associated with organ size control. Research on YAP has focused on its oncogenic...
Yes-associated protein (YAP) is one of the Hippo pathway's two effectors, a pathway associated with organ size control. Research on YAP has focused on its oncogenic potential. However, in cancer cells, aside from inducing growth, YAP was also found to regulate glucose metabolism. The present review explores YAP's control of glucose metabolism and whether these findings are translatable to physiological conditions. According to current literature, YAP induces the transcriptional activity of most genes associated with glucose metabolism from enzymes to transport proteins. In glycolysis and gluconeogenesis, YAP upregulates all enzymes except for enolase and pyruvate kinase. Multiple research has also shown YAP's ability to regulate the expression of glucose transporter of the GLUT family. Additionally, glucose concentration, hypoxia, and hormones such as insulin and glucagon regulate YAP activity and depend on YAP to exert their biological activity. YAP is thus a central regulator of glucose metabolism, controlling both enzymes and proteins involved in glucose transport. YAP is also situated strategically in several pathways controlling glucose and was found to mediate their effects. If these results were consistent in physiological conditions and across glucose-associated metabolic disturbances, then YAP may become a prospective therapeutic target.
Topics: Animals; Gluconeogenesis; Glucose; Glycolysis; Humans; Intracellular Signaling Peptides and Proteins; Signal Transduction; Transcription Factors
PubMed: 33914443
DOI: 10.33594/000000359