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Oral Oncology Aug 2009Oral dysplasia is a potentially precancerous lesion diagnosed histologically. While the risk of progression is associated with histological grade, it is currently... (Review)
Review
Oral dysplasia is a potentially precancerous lesion diagnosed histologically. While the risk of progression is associated with histological grade, it is currently impossible to predict accurately which lesions will progress. More accurate markers predicting progression to cancer would enable the targeting of these lesions for more aggressive treatment and closer follow-up. We have performed a systematic review with pooling of data to assess the evidence for the use of biomarkers in predicting transformation of oral dysplasia into cancer. We systematically searched the Cochrane library, MEDLINE, EMBASE, AMED, Cinahl and the Kings Fund electronic databases using the terms: oral dysplasia, leukoplakia, erythroplakia, biomarkers and genetic markers. The following a priori selection criteria were used: longitudinal cohort or case-controlled studies of oral dysplasia that progressed to cancer. Cross-sectional studies and studies reporting only on leukoplakia were excluded. Data were extracted by two reviewers. Quality assessment was carried out using validated tools. We assessed the relative risk of progression form oral dysplasia to cancer and pooled data where possible. 2550 studies were identified, from which 288 were scrutinised in greater detail. Of these, 247 were excluded, mainly due to cross-sectional design. Of the 41 studies containing follow-up data, 28 were excluded, most commonly due to data only being available for lesions once they had progressed to cancer. A lack of clear histological definition of oral lesions was also a common finding. Data were extracted from 13 longitudinal studies. The evidence consists mainly of small, single centre, retrospective studies. In oral dysplasia, loss of heterozygosity (LOH), particularly at the 3p+/-9p loci, increases the risk of progression to cancer (RR 17.60 (2.77, 108.37) p<0.001), as does survivin (RR 30 (4.25, 197.73), p0.001), matrix metalloproteinase (MMP 9), (RR 19.00 (1.56, 209.38) p=0.02) and DNA content (RR 12.00 (1.17, 82.10) p=0.03). Other markers identified by this review including p53, p73, MMP 1 and 2 and cathepsin L mRNA, did not predict progression. LOH, survivin, MMP 9 and DNA content are potential markers for increased risk of progression from oral dysplasia to cancer. Many methodological limitations have been identified by this review, however, and we recommend these results are interpreted with caution. Research into this field should concentrate on longitudinal design, with pooling of data from multiple centres to achieve larger cohorts. We recommend standardisation of definitions to allow appropriate comparisons to be made.
Topics: Biomarkers; Disease Progression; Genetic Markers; Humans; Mouth; Mouth Diseases; Precancerous Conditions
PubMed: 19442563
DOI: 10.1016/j.oraloncology.2009.02.006 -
Cancer Immunology, Immunotherapy : CII Oct 2009This review summarizes studies on humoral immune responses against tumor-associated antigens (TAAs) with a focus on antibody frequencies and the potential diagnostic,... (Review)
Review
This review summarizes studies on humoral immune responses against tumor-associated antigens (TAAs) with a focus on antibody frequencies and the potential diagnostic, prognostic, and etiologic relevance of antibodies against TAAs. We performed a systematic literature search in Medline and identified 3,619 articles on humoral immune responses and TAAs. In 145 studies, meeting the inclusion criteria, humoral immune responses in cancer patients have been analyzed against over 100 different TAAs. The most frequently analyzed antigens were p53, MUC1, NY-ESO-1, c-myc, survivin, p62, cyclin B1, and Her2/neu. Antibodies against these TAAs were detected in 0-69% (median 14%) of analyzed tumor patients. Antibody frequencies were generally very low in healthy individuals, with the exception of few TAAs, especially MUC1. For several TAAs, including p53, Her2/neu, and NY-ESO-1, higher antibody frequencies were reported when tumors expressed the respective TAA. Antibodies against MUC1 were associated with a favorable prognosis while antibodies against p53 were associated with poor disease outcome. These data suggest different functional roles of endogenous antibodies against TAAs. Although data on prediagnostic antibody levels are scarce and antibody frequencies for most TAAs are at levels precluding use in diagnostic assays for cancer early detection, there is some promising data on achieving higher sensitivity for cancer detection using panels of TAAs.
Topics: Animals; Antibodies, Neoplasm; Antibody Formation; Antigens, Neoplasm; Autoantibodies; Humans; Neoplasm Proteins; Neoplasms
PubMed: 19562338
DOI: 10.1007/s00262-009-0733-4 -
BioMed Research International 2022Endometrial cancer (EC) is one of the most common gynecologic malignancy, mostly in postmenopausal women. The gold standard treatment for EC is surgery, but in the early... (Review)
Review
BACKGROUND
Endometrial cancer (EC) is one of the most common gynecologic malignancy, mostly in postmenopausal women. The gold standard treatment for EC is surgery, but in the early stages, it is possible to opt for conservative treatment. In the last decade, different clinical and pathological markers have been studied to identify women who respond to conservative treatment. A lot of immunohistochemical markers have been evaluated to predict response to progestin treatment, even if their usefulness is still unclear; the prognosis of this neoplasm depends on tumor stage, and a specific therapeutic protocol is set according to the stage of the disease.
OBJECTIVE
(1) To provide an overview of the conservative management of Stage 1A Grade (G) 2 endometrioid EC (FIGO) and the oncological and reproductive outcomes related; (2) to describe the molecular alterations before and after progestin therapy in patients undergoing conservative treatment.
MATERIALS AND METHODS
A systematic computerized search of the literature was performed in the main electronic databases (MEDLINE, Embase, Web of Science, PubMed, and Cochrane Library), from 2010 to September 2021, in order to evaluate the oncological and reproductive outcomes in patients with G2 stage IA EC who ask for fertility-sparing treatment. The expression of several immunohistochemical markers was evaluated in pretreatment phase and during the follow-up in relation to response to hormonal therapy. Only scientific publications in English were included. The risk of bias assessment was performed. Review authors' judgments were categorized as "low risk," "high risk," or "unclear risk" of bias.
RESULTS
Twelve articles were included in the study: 7 observational studies and 5 case series/reports. Eighty-four patients who took progestins (megestrol acetate, medroxyprogesterone acetate, and/or levonorgestrel-releasing intrauterine devices) were analyzed. The publication bias analysis turned out to be "low." 54/84 patients had a complete response, 23/84 patients underwent radical surgery, and 20/84 had a relapse after conservative treatment. Twenty-two patients had a pregnancy. The length of follow-up was variable, from 6 to 142 months according to the different studies analyzed. Several clinical and pathological markers have been studied to identify women who do not respond to conservative treatment: PR and ER were the most studied predictive markers, in particular PR appeared as the most promising; MMR, SPAG9, Ki67, and Nrf2-survivin pathway provided good results with a significant association with a good response to progestin therapy. However, no reliable predictive markers are currently available to be used in clinical practice.
CONCLUSIONS
The conservative treatment may be an option for patients with stage IA G2 EEC who desire to preserve their fertility. The immunohistochemical markers evaluation looks promising in predicting response to conservative treatment. Further large series and randomized clinical trials are needed to confirm these results.
Topics: Adaptor Proteins, Signal Transducing; Antineoplastic Agents, Hormonal; Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Fertility Preservation; Humans; Ki-67 Antigen; Levonorgestrel; Medroxyprogesterone Acetate; Megestrol Acetate; NF-E2-Related Factor 2; Neoplasm Recurrence, Local; Pregnancy; Progestins; Survivin
PubMed: 36203482
DOI: 10.1155/2022/4070368 -
Cellular Physiology and Biochemistry :... 2018Recently, many studies have demonstrated that various tumor-associated autoantibodies have been detected in early stages of lung cancer. Therefore, we conducted a... (Meta-Analysis)
Meta-Analysis
BACKGROUND/AIMS
Recently, many studies have demonstrated that various tumor-associated autoantibodies have been detected in early stages of lung cancer. Therefore, we conducted a meta-analysis to comprehensively evaluate available evidence on the diagnostic value of autoantibodies against tumor-associated antigens in lung cancer.
METHODS
We systematically searched PubMed, Scopus, Web of Science and other databases through 23 March 2018. Study quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies-2. We used the bivariate mixed-effect models to calculate pooled values of sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, diagnostic odds ratios and associated 95% confidence intervals. Summary receiver operating characteristic (SROC) curves were used to summarize overall test performance. Deek's funnel plot was used to detect publication bias.
RESULTS
Review of 468 candidate articles identified fifty-three articles with a total of 11,515 patients for qualitative review and meta-analysis. Pooled sensitivity, specificity and area under the SROC curve were as follows for tumor-associated autoantibodies against the following proteins: p53, 0.19, 0.98, 0.82; NY-ESO-1, 0.17, 0.98, 0.90; Survivin, 0.19, 0.99, 0.96; c-myc, 0.14, 0.98, 0.45; Cyclin B1, 0.18, 0.98, 0.91; GBU4-5, 0.07, 0.98, 0.91; CAGE, 0.14, 0.98, 0.90; p16, 0.08, 0.97, 0.91; SOX2, 0.14, 0.99, 0.93; and HuD, 0.17, 0.99, 0.82.
CONCLUSION
Each tumor-associated autoantibody on its own showed excellent diagnostic specificity for lung cancer but inadequate sensitivity. Our results suggest that combinations or panels of tumor-associated autoantibodies may provide better sensitivity for diagnosing lung cancer, and the diagnostic accuracy of tumor-associated autoantibodies should be validated in more studies.
Topics: Autoantibodies; Biomarkers, Tumor; Humans; Lung Neoplasms; Neoplasm Staging; ROC Curve
PubMed: 30562746
DOI: 10.1159/000495935 -
Molecular Biology Reports Feb 2013Among new biological markers that could become useful prognostic factors for non-small cell lung cancer (NSCLC). Survivin is one of the most commonly over-expressed... (Meta-Analysis)
Meta-Analysis
Among new biological markers that could become useful prognostic factors for non-small cell lung cancer (NSCLC). Survivin is one of the most commonly over-expressed oncogenes, however, its role in NSCLC remains controversial. We performed a systematic review of the literature with meta-analysis to clarify this issue. Electronic databases were used to identify published studies before August 2011. Pooled hazard ratio (HR) with 95 % confidence interval (95 % CI) was used to estimate the strength of the association of survivin expression with survival of NSCLC patients. Heterogeneity and publication bias were also assessed. Overall 29 relevant published studies including 2,517 lung cancer patients were identified from electronic databases. We found that overexpression of survivin in NSCLC patients might be a poor prognostic factor for survival 1.95 (95 % CI: 1.65-2.29; P < 0.001). Heterogeneity testing indicated that there was heterogeneity among studies. When stratified by histology types, the heterogeneity was absent. We should point out that the publication bias may partly account for the result, but the conclusion might not be affected deeply by the publication bias. When we accounted for publication bias using the trim and fill method, the results remained significant (HR = 1.71, 95 % CI: 1.44-2.02, P < 0.001), suggesting the stability of our results. Therefore, our study suggested that survivin overexpression had a poor prognosis value in patients with NSCLC.
Topics: Carcinoma, Non-Small-Cell Lung; Gene Expression; Humans; Inhibitor of Apoptosis Proteins; Lung Neoplasms; Publication Bias; Survivin
PubMed: 23065255
DOI: 10.1007/s11033-012-2132-8 -
Diagnostics (Basel, Switzerland) Jan 2023Neurogenic lower urinary tract dysfunction requires lifelong surveillance and management for the perseveration of patients' quality of life and the prevention of... (Review)
Review
BACKGROUND
Neurogenic lower urinary tract dysfunction requires lifelong surveillance and management for the perseveration of patients' quality of life and the prevention of significant morbidity and mortality. Urine biomarkers are an attractive noninvasive method of surveillance for these patients. The aim of this systematic review is to search for and critically appraise studies that investigate the clinical usefulness of urine biomarkers in the management of neurogenic lower urinary tract dysfunction (NLUTD) in adults.
METHODS
This review was conducted according to PRISMA and MOOSE guidelines. Search strategy included PubMed, CENTRAL, and Scopus (until October 2022). Studies investigating potential urine biomarkers for the management of adults with NLUTD were included.
RESULTS
Fifteen studies fulfilled the criteria. To date, a variety of different urine molecules have been investigated for the diagnosis and management of neurogenic overactive bladder and detrusor overactivity (nerve growth factor, brain-derived neurotrophic factor, prostaglandin E2, prostaglandin F2α, transformation growth factor β-1, tissue inhibitor metalloproteinase-2, matrix metalloproteinase-2, substance P, microRNA), diagnosis of vesicoureteral reflux (exosomal vitronectin), urinary tract infection (neutrophil gelatinase-associated lipocalin, interleukin 6) and bladder cancer screening (cytology, BTA stat, survivin) in neurological patients.
CONCLUSION
Further studies are needed to specify the utility of each molecule in the management algorithm of adult NLUTD.
PubMed: 36766573
DOI: 10.3390/diagnostics13030468 -
Frontiers in Veterinary Science 2020Canine and human bladder cancer present similar anatomical, morphological, and molecular characteristics, and dogs can be considered a model for human bladder cancer....
Canine and human bladder cancer present similar anatomical, morphological, and molecular characteristics, and dogs can be considered a model for human bladder cancer. However, the veterinary literature lacks information regarding cross-validation analysis between human and canine large-scale data. Therefore, this research aimed to perform a meta-analysis of the canine literature on bladder cancer, identifying genes and proteins previously evaluated in these studies. In addition, we also performed a cross-validation of the canine transcriptome data and the human data from The Cancer Genome Atlas (TCGA) to identify potential markers for both species. The meta-analysis was performed using the following indexing terms: "bladder" AND "carcinoma" AND "dog" in different international databases, and 385 manuscripts were identified in our initial search. Then, several inclusion criteria were applied, and only 25 studies met these criteria. Among these studies, five presented transcriptome data, and 20 evaluated only isolated genes or proteins. Regarding the studies involving isolated protein analysis, the HER-2 protein was the most studied (3/20), followed by TAG-72 (2/20), COX-2 (2/20), survivin (2/20), and CK7 (2/20), and the remaining nine studies evaluated one isolated protein each. Regarding the cross-validation analysis of human and canine transcriptome data, we identified 35 dysregulated genes, including , and . Our results demonstrate that the canine literature on bladder cancer previously focused on the evaluation of isolated markers with no association with patient survival. This limitation may be related to the lack of a homogenous protocol for treating patients and the lack of follow-up during treatment. In addition, the lack of information regarding tumor muscle invasion can be considered an important limitation when comparing human and canine bladder tumors. Our analysis involving canine and human transcriptome data provided several genes with the potential to be markers for both human and canine bladder tumors, and these genes should be considered for future studies on canine bladder cancer.
PubMed: 33304937
DOI: 10.3389/fvets.2020.558978 -
Clinica Chimica Acta; International... Feb 2015Survivin in pleural effusion is a promising marker for the diagnosis of malignant pleural effusion. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Survivin in pleural effusion is a promising marker for the diagnosis of malignant pleural effusion.
METHODS
Based on the principles and methods of Cochrane systematic reviews, PubMed, EMBASE, Web of Knowledge (ISI), the Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases were searched to identify studies that assessed the diagnostic value of survivin in pleural effusion for malignant pleural effusion. Stata 12 and Meta-disc 1.4 software were used to test the heterogeneity and to perform the meta-analysis.
RESULTS
Our search returned 167 articles, of which ten fulfilled the inclusion criteria. These studies included a total of 614 patients with malignant pleural effusion and 430 patients with benign pleural effusion as controls. The summary assessments revealed that the pooled sensitivity was 0.86 (95% CI: 0.82-0.88) and the pooled specificity was 0.92 (95% CI: 0.89-0.94). The positive likelihood ratio was 8.76 (95% CI: 5.41-14.20), the negative likelihood ratio was 0.16 (95% CI: 0.13-0. 20) and the diagnostic odds ratio (DOR) was 59.72 (95% CI: 39.60-90.05). The area under the curve (AUC) for the pleural effusion survivin tests was 0.9485, and the *Q index estimate for these tests was 0.8885.
CONCLUSIONS
Survivin in pleural effusion has potential diagnostic value with advanced sensitivity and specificity and it can be used as adjunct tool for non-invasive diagnosis of malignant pleural effusion.
Topics: Humans; Inhibitor of Apoptosis Proteins; Pleural Effusion, Malignant; Survivin
PubMed: 25559946
DOI: 10.1016/j.cca.2014.12.029 -
PloS One 2013The expression of survivin is a promising prognostic indicator for some carcinomas. However, evidence for the prognostic value of survivin with respect to survival in... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The expression of survivin is a promising prognostic indicator for some carcinomas. However, evidence for the prognostic value of survivin with respect to survival in hepatocellular carcinoma remains controversial.
AIM
To conduct a systematic review of studies evaluating survivin expression in hepatocellular carcinoma as a prognostic indicator.
METHODS
The relevant literature was searched using PubMed, EMBASE, and Chinese biomedicine databases, and two meta-analyses were performed. One studied the association between survivin expression and the overall survival of patients with hepatocellular carcinoma, whereas the other studied the association between survivin expression and disease-free survival. Studies were pooled, and summary hazard ratios (HRs) were calculated. Subgroup analyses were also conducted.
RESULTS
Fourteen eligible studies with a total of 890 patients were included in this study. Two meta-analyses were performed according to the different outcomes by which prognosis was valued. The combined HR of the overall survival studies was 2.33 (95% CI: 1.65-3.31). The combined HR of disease-free survival studies was 2.13 (95% CI: 1.65-2.75). These data appeared to be significant when stratified by detection method, the language of publication, and HR estimate. The heterogeneities were highly significant (I(2)>50%) when subgroup analyses of overall survival rate were conducted, whereas little heterogeneity was found when subgroup analyses of disease-free survival rate were carried out. The positive expression of survivin in the cytoplasm was significantly correlated with poor prognosis in HCC (HR>1).
CONCLUSIONS
This study showed that survivin expression was correlated with poor prognosis in patients with hepatocellular carcinoma, regardless whether they were assessed by overall survival or disease-free survival.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Humans; Inhibitor of Apoptosis Proteins; Liver Neoplasms; Prognosis; Proportional Hazards Models; Publication Bias; Survivin
PubMed: 24386184
DOI: 10.1371/journal.pone.0083350 -
Journal of Molecular Histology Jun 2024The prevalence of TNBC in India is higher compared to western countries. There is a multitude of biomarkers associated with different clinical outcomes of TNBC with... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The prevalence of TNBC in India is higher compared to western countries. There is a multitude of biomarkers associated with different clinical outcomes of TNBC with contradictory reports. Identification of a set of specific biomarkers from the very many number of proteins reported in the literature to predict prognosis of TNBC is an urgent clinical need.
METHODOLOGY
A systematic review of key molecular biomarkers in cohort studies that have been investigated for their role in breast cancer prognosis was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology was followed. A meta-analysis was used to evaluate their pooled hazard ratio (HR) and the corresponding 95% confidence interval (95% CI) statistically. Immunohistochemical characterization of the meta-analyzed markers were performed in a cohort of 200 retrospective TNBC and 100 non TNBC patient tissues. Kaplan-Meier plot were used to evaluate disease free survival (DFS), and overall survival (OS). Cox regression models were used to evaluate predictors of DFS and OS.
RESULTS
Using a meta-analytical approach, we consolidated the biomarker signatures associated with survival outcomes in breast cancers. The promising markers that emerged for the prediction of DFS and OS included E-Cadherin, Survivin, p53, MTA1, HIF1A, CD133, Vimentin and CK5/6. Evaluation of these markers in tumor tissue revealed that subcellular localization of p53, MTA1 and HIF1A had a significant association in predicting TNBC prognosis. Kaplan Meier plot revealed that p53 (OS p = 0.007, DFS p = 0.004), HIF 1 A (OS p = 0.054, DFS p = 0.009) and MTA1 (OS p = 0.043, DFS = p = 0.001) expression in the primary tumor tissue were found to be significantly correlated with poor OS and DFS, whereas expression of Survivin (DFS p = 0.024) and E Cadherin (DFS p = 0.027) correlated with DFS alone in TNBC. Univariate analysis revealed that p53, HIF1A and MTA1 could be independent prognostic markers.
CONCLUSION
Our study suggests cytoplasmic over expression of HIF1A, nuclear over expression of MTA1 and mutated p53 in the primary tumor tissue of TNBC have significance as markers predicting survival of TNBC patients.
Topics: Humans; Triple Negative Breast Neoplasms; Tumor Suppressor Protein p53; Repressor Proteins; Biomarkers, Tumor; Female; Trans-Activators; Hypoxia-Inducible Factor 1, alpha Subunit; Histone Deacetylases; Prognosis; Kaplan-Meier Estimate
PubMed: 38613589
DOI: 10.1007/s10735-024-10190-9