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The Cochrane Database of Systematic... Sep 2018This is the second update of the review first published in the Cochrane Library (2010, Issue 2) and later updated (2014, Issue 9).Despite advances in chemotherapy, the... (Review)
Review
BACKGROUND
This is the second update of the review first published in the Cochrane Library (2010, Issue 2) and later updated (2014, Issue 9).Despite advances in chemotherapy, the prognosis of ovarian cancer remains poor. Antigen-specific active immunotherapy aims to induce tumour antigen-specific anti-tumour immune responses as an alternative treatment for ovarian cancer.
OBJECTIVES
Primary objective• To assess the clinical efficacy of antigen-specific active immunotherapy for the treatment of ovarian cancer as evaluated by tumour response measured by Response Evaluation Criteria In Solid Tumors (RECIST) and/or cancer antigen (CA)-125 levels, response to post-immunotherapy treatment, and survival differences◦ In addition, we recorded the numbers of observed antigen-specific humoral and cellular responsesSecondary objective• To establish which combinations of immunotherapeutic strategies with tumour antigens provide the best immunological and clinical results SEARCH METHODS: For the previous version of this review, we performed a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL; 2009, Issue 3), in the Cochrane Library, the Cochrane Gynaecological Cancer Group Specialised Register, MEDLINE and Embase databases, and clinicaltrials.gov (1966 to July 2009). We also conducted handsearches of the proceedings of relevant annual meetings (1996 to July 2009).For the first update of this review, we extended the searches to October 2013, and for this update, we extended the searches to July 2017.
SELECTION CRITERIA
We searched for randomised controlled trials (RCTs), as well as non-randomised studies (NRSs), that included participants with epithelial ovarian cancer, irrespective of disease stage, who were treated with antigen-specific active immunotherapy, irrespective of type of vaccine, antigen used, adjuvant used, route of vaccination, treatment schedule, and reported clinical or immunological outcomes.
DATA COLLECTION AND ANALYSIS
Two reviews authors independently extracted the data. We evaluated the risk of bias for RCTs according to standard methodological procedures expected by Cochrane, and for NRSs by using a selection of quality domains deemed best applicable to the NRS.
MAIN RESULTS
We included 67 studies (representing 3632 women with epithelial ovarian cancer). The most striking observations of this review address the lack of uniformity in conduct and reporting of early-phase immunotherapy studies. Response definitions show substantial variation between trials, which makes comparison of trial results unreliable. Information on adverse events is frequently limited. Furthermore, reports of both RCTs and NRSs frequently lack the relevant information necessary for risk of bias assessment. Therefore, we cannot rule out serious biases in most of the included trials. However, selection, attrition, and selective reporting biases are likely to have affected the studies included in this review. GRADE ratings were high only for survival; for other primary outcomes, GRADE ratings were very low.The largest body of evidence is currently available for CA-125-targeted antibody therapy (17 studies, 2347 participants; very low-certainty evidence). Non-randomised studies of CA-125-targeted antibody therapy suggest improved survival among humoral and/or cellular responders, with only moderate adverse events. However, four large randomised placebo-controlled trials did not show any clinical benefit, despite induction of immune responses in approximately 60% of participants. Time to relapse with CA-125 monoclonal antibody versus placebo, respectively, ranged from 10.3 to 18.9 months versus 10.3 to 13 months (six RCTs, 1882 participants; high-certainty evidence). Only one RCT provided data on overall survival, reporting rates of 80% in both treatment and placebo groups (three RCTs, 1062 participants; high-certainty evidence). Other small studies targeting many different tumour antigens have presented promising immunological results. As these strategies have not yet been tested in RCTs, no reliable inferences about clinical efficacy can be made. Given the promising immunological results and the limited side effects and toxicity reported, exploration of clinical efficacy in large well-designed RCTs may be worthwhile.
AUTHORS' CONCLUSIONS
We conclude that despite promising immunological responses, no clinically effective antigen-specific active immunotherapy is yet available for ovarian cancer. Results should be interpreted cautiously, as review authors found a significant dearth of relevant information for assessment of risk of bias in both RCTs and NRSs.
Topics: CA-125 Antigen; Female; Humans; Immunotherapy, Active; Neoplasm Recurrence, Local; Neoplasms, Glandular and Epithelial; Ovarian Neoplasms
PubMed: 30199097
DOI: 10.1002/14651858.CD007287.pub4 -
European Urology Jul 2023The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for...
Impact of Epithelial Histological Types, Subtypes, and Growth Patterns on Oncological Outcomes for Patients with Nonmetastatic Prostate Cancer Treated with Curative Intent: A Systematic Review.
CONTEXT
The optimal management for men with prostate cancer (PCa) with unconventional histology (UH) is unknown. The outcome for these cancers might be worse than for conventional PCa and so different approaches may be needed.
OBJECTIVE
To compare oncological outcomes for conventional and UH PCa in men with localized disease treated with curative intent.
EVIDENCE ACQUISITION
A systematic review adhering to the Referred Reporting Items for Systematic Reviews and Meta-Analyses was prospectively registered on PROSPERO (CRD42022296013) was performed in July 2021.
EVIDENCE SYNTHESIS
We screened 3651 manuscripts and identified 46 eligible studies (reporting on 1 871 814 men with conventional PCa and 6929 men with 10 different PCa UHs). Extraprostatic extension and lymph node metastases, but not positive margin rates, were more common with UH PCa than with conventional tumors. PCa cases with cribriform pattern, intraductal carcinoma, or ductal adenocarcinoma had higher rates of biochemical recurrence and metastases after radical prostatectomy than for conventional PCa cases. Lower cancer-specific survival rates were observed for mixed cribriform/intraductal and cribriform PCa. By contrast, pathological findings and oncological outcomes for mucinous and prostatic intraepithelial neoplasia (PIN)-like PCa were similar to those for conventional PCa. Limitations of this review include low-quality studies, a risk of reporting bias, and a scarcity of studies that included radiotherapy.
CONCLUSIONS
Intraductal, cribriform, and ductal UHs may have worse oncological outcomes than for conventional and mucinous or PIN-like PCa. Alternative treatment approaches need to be evaluated in men with these cancers.
PATIENT SUMMARY
We reviewed the literature to explore whether prostate cancers with unconventional growth patterns behave differently to conventional prostate cancers. We found that some unconventional growth patterns have worse outcomes, so we need to investigate if they need different treatments. Urologists should be aware of these growth patterns and their clinical impact.
Topics: Humans; Male; Prostate; Prostate-Specific Antigen; Prostatectomy; Prostatic Intraepithelial Neoplasia; Prostatic Neoplasms
PubMed: 37117107
DOI: 10.1016/j.eururo.2023.03.014 -
Fish & Shellfish Immunology Nov 2022Nanoparticles-based treatments is of utmost importance for aquaculture. In this scenario, chitosan-based nanoparticles have been proposed due to the properties of... (Review)
Review
Nanoparticles-based treatments is of utmost importance for aquaculture. In this scenario, chitosan-based nanoparticles have been proposed due to the properties of chitosan, which include mucoadhesiveness. Nevertheless, pivotal parameters of chitosan, such as degree of acetylation and molecular weight, are commonly underestimated in the available literature despite the influence they seem to have on the properties of chitosan-based nanoparticles. In this systematic review, the immunomodulator capacity of chitosan nanoparticles used as mucosal vaccines on teleost fish has been evaluated paying special attention to the chitosan properties. Four databases were used for literature search, yielding 486 documents, from which 14 meet the inclusion criteria. Only 21% of the available studies reported properly chitosan properties, which should be improved in future works to generate reproducible data as well as valuable information. To the best of our knowledge, this work objectively compares for the first time, by quantifying the mg of chitosan/g of fish applied in each study, the chitosan nanoparticle preparation and doses applied to fish, as well as the effects of the treatments applied on fish immune status.
Topics: Adjuvants, Immunologic; Animals; Chitosan; Immunity, Mucosal; Nanoparticles; Vaccines
PubMed: 36038102
DOI: 10.1016/j.fsi.2022.08.030 -
International Journal of Surgery... Jul 2023The best approach for treating benign or low-grade malignant lesions localized in the pancreatic neck or body remains debatable. Conventional pancreatoduodenectomy and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The best approach for treating benign or low-grade malignant lesions localized in the pancreatic neck or body remains debatable. Conventional pancreatoduodenectomy and distal pancreatectomy (DP) are associated with a risk of impairment of pancreatic function at long-term follow-up. With advances in technology and surgical skills, the use of central pancreatectomy (CP) has gradually increased.
OBJECTIVES
The objective was to compare the safety, feasibility, and short-term and long-term clinical benefits of CP and DP in matched cases.
METHODS
The PubMed, MEDLINE, Web of Science, Cochrane, and EMBASE databases were systematically searched to identify studies published from database inception to February 2022 that compared CP and DP. This meta-analysis was performed using R software.
RESULTS
Twenty-six studies matched the selection criteria, including 774 CP and 1713 DP cases. CP was significantly associated with longer operative time ( P <0.0001), less blood loss ( P <0.01), overall and clinically relevant pancreatic fistula ( P <0.0001), postoperative hemorrhage ( P <0.0001), reoperation ( P =0.0196), delayed gastric emptying ( P =0.0096), increased hospital stay ( P =0.0002), intra-abdominal abscess or effusion ( P =0.0161), higher morbidity ( P <0.0001) and severe morbidity ( P <0.0001) but with a significantly lower incidence of overall endocrine and exocrine insufficiency ( P <0.01), and new-onset and worsening diabetes mellitus ( P <0.0001) than DP.
CONCLUSIONS
CP should be considered as an alternative to DP in selected cases such as without pancreatic disease, length of the residual distal pancreas is more than 5 cm, branch-duct intraductal papillary mucinous neoplasms, and a low risk of postoperative pancreatic fistula after adequate evaluation.
Topics: Humans; Pancreatectomy; Pancreatic Fistula; Retrospective Studies; Pancreas; Pancreatic Neoplasms; Postoperative Complications
PubMed: 37300889
DOI: 10.1097/JS9.0000000000000326 -
Discover Oncology Feb 2021Histological subtypes of colorectal cancer may be associated with varied prognostic features. This systematic review and meta-analysis aimed to compare... (Review)
Review
Clinicopathological factors and survival outcomes of signet-ring cell and mucinous carcinoma versus adenocarcinoma of the colon and rectum: a systematic review and meta-analysis.
BACKGROUND
Histological subtypes of colorectal cancer may be associated with varied prognostic features. This systematic review and meta-analysis aimed to compare clinicopathological characteristics, recurrence and overall survival between colorectal signet-ring cell (SC) and mucinous carcinoma (MC) to conventional adenocarcinoma (AC).
METHODS
A literature search of MEDLINE, EMBASE, Ovid and Cochrane Library was performed for studies that reported data on clinicopathological and survival outcomes on SC and/or MC versus AC from January 1985 to May 2020. Meta-analysis was performed using random-effect models and between-study heterogeneity was assessed.
RESULTS
Thirty studies of 1,087,055 patients were included: 11,510 (1.06%) with SC, 110,179 (10.13%) with MC and 965,366 (88.81%) with AC. Patients with SC were younger than patients with AC (WMD - 0.47; 95% CI - 0.84 to -0.10; I 88.6%; p = 0.014) and more likely to have right-sided disease (OR 2.12; 95% CI 1.72-2.60; I 82.9%; p < 0.001). Locoregional recurrence at 5 years was more frequent in patients with SC (OR 2.81; 95% CI 1.40-5.65; I 0.0%; p = 0.004) and MC (OR 1.92; 95% CI 1.18-3.15; I 74.0%; p = 0.009). 5-year overall survival was significantly reduced when comparing SC and MC to AC (HR 2.54; 95% CI 1.98-3.27; I 99.1%; p < 0.001 and HR 1.38; 95% CI 1.19-1.61; I 98.6%; p < 0.001, respectively).
CONCLUSION
SC and MC are associated with right-sided lesions, advanced stage at presentation, higher rates of recurrence and poorer overall survival. This has strong implications towards surgical and oncological management and surveillance of colorectal cancer.
PubMed: 35201441
DOI: 10.1007/s12672-021-00398-6 -
Current Issues in Molecular Biology May 2024The activity of dental caries, combined with its multifactorial etiology, alters salivary molecule composition. The present systematic review was developed to answer the... (Review)
Review
The activity of dental caries, combined with its multifactorial etiology, alters salivary molecule composition. The present systematic review was developed to answer the following question: "Are salivary biomarkers reliable for diagnosis of dental caries?". Following the "Preferred Reporting Item for Systematic Reviews and Meta-analysis" (PRISMA) guidelines, the review was conducted using multiple database research (Medline, Web of Science, and Scopus). Studies performed on healthy subjects with and without dental caries and providing detailed information concerning the clinical diagnosis of caries (Decayed, Missing, Filled Teeth-DMFT and International Caries Detection and Assessment System-ICDAS criteria) were included. The quality assessment was performed following a modified version of the Joanna Briggs Institute Prevalence Critical Appraisal Checklist. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, ID: CRD42022304505). Sixteen papers were included in the review. All studies reported statistically significant differences in the concentration of salivary molecules between subjects with and without caries ( < 0.05). Proteins were the most investigated molecules, in particular alpha-amylase and mucins. Some studies present a risk of bias, such as identifying confounding factors and clearly defining the source population. Nevertheless, the 16 papers were judged to be of moderate to high quality. There is evidence that some salivary compounds studied in this review could play an important diagnostic role for dental caries, such as salivary mucins, glycoproteins (sCD14), interleukins (IL-2RA, 4,-13), urease, carbonic anhydrase VI, and urea.
PubMed: 38785526
DOI: 10.3390/cimb46050258 -
Medicina (Kaunas, Lithuania) Jul 2022Pancreatic cystic lesions (PCLs) are frequently incidental findings. The prevalence of PCLs is increasing, mainly due to advancements in imaging techniques, but also... (Review)
Review
Pancreatic cystic lesions (PCLs) are frequently incidental findings. The prevalence of PCLs is increasing, mainly due to advancements in imaging techniques, but also because of the aging of the population. PCLs comprise challenging clinical problems, as their manifestations vary from benign to malignant lesions. Therefore, the recognition of PCLs is achieved through a complex diagnostic and surveillance process, which in turn is usually long-term, invasive, and expensive. Despite the progress made in the identification of novel biomarkers in the cystic fluid that also support the differentiation of PCLs, their application in clinical practice is limited. We conducted a systematic review of the literature published in two databases, Pubmed and Embase, on biochemical biomarkers in PCLs that may be applied in the diagnostic algorithms of PCLs. Eleven studies on intracystic glucose, twenty studies on intracystic carcinoembryonic antigen (CEA), and eighteen studies on other biomarkers were identified. Low levels of intracystic glucose had high sensitivity and specificity in the differentiation between mucinous and non-mucinous cystic neoplasms. CEA and glucose are the most widely studied fluid biochemical markers in pancreatic cystic lesions. Glucose has better diagnostic accuracy than CEA. Other biochemical biomarkers require further research.
Topics: Biomarkers, Tumor; Carcinoembryonic Antigen; Diagnosis, Differential; Glucose; Humans; Pancreatic Cyst; Pancreatic Neoplasms
PubMed: 35893110
DOI: 10.3390/medicina58080994 -
The Cochrane Database of Systematic... Jul 2016About 10% of women of reproductive age suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard... (Review)
Review
BACKGROUND
About 10% of women of reproductive age suffer from endometriosis, a costly chronic disease causing pelvic pain and subfertility. Laparoscopy is the gold standard diagnostic test for endometriosis, but is expensive and carries surgical risks. Currently, there are no non-invasive tests available in clinical practice to accurately diagnose endometriosis. This review assessed the diagnostic accuracy of combinations of different non-invasive testing modalities for endometriosis and provided a summary of all the reviews in the non-invasive tests for endometriosis series.
OBJECTIVES
To estimate the diagnostic accuracy of any combination of non-invasive tests for the diagnosis of pelvic endometriosis (peritoneal and/or ovarian or deep infiltrating) compared to surgical diagnosis as a reference standard. The combined tests were evaluated as replacement tests for diagnostic surgery and triage tests to assist decision-making to undertake diagnostic surgery for endometriosis.
SEARCH METHODS
We did not restrict the searches to particular study designs, language or publication dates. We searched CENTRAL to July 2015, MEDLINE and EMBASE to May 2015, as well as the following databases to April 2015: CINAHL, PsycINFO, Web of Science, LILACS, OAIster, TRIP, ClinicalTrials.gov, DARE and PubMed.
SELECTION CRITERIA
We considered published, peer-reviewed, randomised controlled or cross-sectional studies of any size, including prospectively collected samples from any population of women of reproductive age suspected of having one or more of the following target conditions: ovarian, peritoneal or deep infiltrating endometriosis (DIE). We included studies comparing the diagnostic test accuracy of a combination of several testing modalities with the findings of surgical visualisation of endometriotic lesions.
DATA COLLECTION AND ANALYSIS
Three review authors independently collected and performed a quality assessment of the data from each study by using the QUADAS-2 tool. For each test, the data were classified as positive or negative for the surgical detection of endometriosis and sensitivity and specificity estimates were calculated. The bivariate model was planned to obtain pooled estimates of sensitivity and specificity whenever sufficient data were available. The predetermined criteria for a clinically useful test to replace diagnostic surgery were a sensitivity of 0.94 and a specificity of 0.79 to detect endometriosis. We set the criteria for triage tests at a sensitivity of 0.95 and above and a specificity of 0.50 and above, which 'rules out' the diagnosis with high accuracy if there is a negative test result (SnOUT test), or a sensitivity of 0.50 and above and a specificity of 0.95 and above, which 'rules in' the diagnosis with high accuracy if there is a positive result (SpIN test).
MAIN RESULTS
Eleven eligible studies included 1339 participants. All the studies were of poor methodological quality. Seven studies evaluated pelvic endometriosis, one study considered DIE and/or ovarian endometrioma, two studies differentiated endometrioma from other ovarian cysts and one study addressed mapping DIE at specific anatomical sites. Fifteen different diagnostic combinations were assessed, including blood, urinary or endometrial biomarkers, transvaginal ultrasound (TVUS) and clinical history or examination. We did not pool estimates of sensitivity and specificity, as each study analysed independent combinations of the non-invasive tests.Tests that met the criteria for a replacement test were: a combination of serum IL-6 (cut-off >15.4 pg/ml) and endometrial PGP 9.5 for pelvic endometriosis (sensitivity 1.00 (95% confidence interval (CI) 0.91 to 1.00), specificity 0.93 (95% CI, 0.80, 0.98) and the combination of vaginal examination and transvaginal ultrasound (TVUS) for rectal endometriosis (sensitivity 0.96 (95% CI 0.86 to 0.99), specificity 0.98 (95% CI 0.94 to 1.00)). Tests that met the criteria for SpIN triage tests for pelvic endometriosis were: 1. a multiplication of urine vitamin-D-binding protein (VDBP) and serum CA-125 (cut-off >2755) (sensitivity 0.74 (95% CI 0.60 to 0.84), specificity 0.97 (95% CI 0.86 to 1.00)) and 2. a combination of history (length of menses), serum CA-125 (cut-off >35 U/ml) and endometrial leukocytes (sensitivity 0.61 (95% CI 0.54 to 0.69), specificity 0.95 (95% CI 0.91 to 0.98)). For endometrioma, the following combinations qualified as SpIN test: 1. TVUS and either serum CA-125 (cut-off ≥25 U/ml) or CA 19.9 (cut-off ≥12 U/ml) (sensitivity 0.79 (95% CI 0.64 to 0.91), specificity 0.97 (95% CI 0.91 to 1.00)); 2. TVUS and serum CA 19.9 (cut-off ≥12 U/ml) (sensitivity 0.54 (95% CI 0.37 to 0.70), specificity 0.97 (95% CI 0.91 to 1.0)); 3-4. TVUS and serum CA-125 (cut-off ≥20 U/ml or cut-off ≥25 U/ml) (sensitivity 0.69 (95% CI 0.49 to 0.85), specificity 0.96 (95% CI 0.88 to 0.99)); 5. TVUS and serum CA-125 (cut-off ≥35 U/ml) (sensitivity 0.52 (95% CI 0.33 to 0.71), specificity 0.97 (95% CI 0.90 to 1.00)). A combination of vaginal examination and TVUS reached the threshold for a SpIN test for obliterated pouch of Douglas (sensitivity 0.87 (95% CI 0.69 to 0.96), specificity 0.98 (95% CI 0.95 to 1.00)), vaginal wall endometriosis (sensitivity 0.82 (95% CI 0.60 to 0.95), specificity 0.99 (95% CI 0.97 to 1.0)) and rectovaginal septum endometriosis (sensitivity 0.88 (95% CI 0.47 to 1.00), specificity 0.99 (95% CI 0.96 to 1.00)).All the tests were evaluated in individual studies and displayed wide CIs. Due to the heterogeneity and high risk of bias of the included studies, the clinical utility of the studied combination diagnostic tests for endometriosis remains unclear.
AUTHORS' CONCLUSIONS
None of the biomarkers evaluated in this review could be evaluated in a meaningful way and there was insufficient or poor-quality evidence. Laparoscopy remains the gold standard for the diagnosis of endometriosis and using any non-invasive tests should only be undertaken in a research setting.
Topics: Aromatase; Biomarkers; CA-125 Antigen; CA-19-9 Antigen; Endometriosis; Female; Humans; Interleukin-6; Leukocytes; Ovarian Diseases; Pelvis; Peritoneal Diseases; Phosphopyruvate Hydratase; Sensitivity and Specificity; Ubiquitin Thiolesterase; Ultrasonography; Vitamin D-Binding Protein
PubMed: 27405583
DOI: 10.1002/14651858.CD012281 -
Medicine Jun 2016Specific diagnostic biomarker for cholangiocarcinoma (CCA) has been lacking. This systematic review and meta-analysis was performed aiming to investigate serum MUC5AC's... (Meta-Analysis)
Meta-Analysis Review
Specific diagnostic biomarker for cholangiocarcinoma (CCA) has been lacking. This systematic review and meta-analysis was performed aiming to investigate serum MUC5AC's diagnostic performance on CCA.Studies investigating serum MUC5AC's diagnostic value on CCA were retrieved from Pubmed, Embase, and Cochrane Library. The methodology quality of included studies was assessed according to QUADAS-2. Diagnostic 2 × 2 table was extracted from each eligible study, Meta-disc 1.4 was used for statistical analysis, data synthesis was done using a random-effects model. Subgroup analyses were conducted according to region and array method.Six eligible studies were identified, a total of 1213 patients were involved in the meta-analysis. The AUC on SROC was 0.9138, and the Q* was 8463. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) were 0.69 (95% CI: 0.65-0.73), 0.93 (95% CI: 0.91-0.95), 8.99 (95% CI: 5.65-14.30), 0.33 (95% CI: 0.24-0.46), and 33.98 (95% CI: 20.12-57.40), respectively. Targeting MUC5AC's epitope has a higher pooled sensitivity than targeting MUC5AC protein (0.77 vs 0.63). There was substantial cross-study heterogeneity.Serum MUC5AC might be potentially used as a surrogate marker in the diagnosis of CCA. However, the appropriate array method and the optimum cut-off value are yet to be decided.
Topics: Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Biomarkers, Tumor; Cholangiocarcinoma; Humans; Mucin 5AC
PubMed: 27310944
DOI: 10.1097/MD.0000000000003513 -
PloS One 2014Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. The B-type Raf proto-oncogene (BRAF) plays an important role in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Colorectal cancer (CRC) is a heterogeneous disease with multiple underlying causative genetic mutations. The B-type Raf proto-oncogene (BRAF) plays an important role in the mitogen-activated protein kinase (MAPK) signaling cascade during CRC. The presence of BRAFV600E mutation can determine the response of a tumor to chemotherapy. However, the association between the BRAFV600E mutation and the clinicopathological features of CRC remains controversial. We performed a systematic review and meta-analysis to estimate the effect of BRAFV600E mutation on the clinicopathological characteristics of CRC.
METHODS
We identified studies that examined the effect of BRAFV600E mutation on CRC within the PubMed, ISI Science Citation Index, and Embase databases. The effect of BRAFV600E on outcome parameters was estimated by odds ratios (ORs) with 95% confidence intervals (CIs) for each study using a fixed effects or random effects model.
RESULTS
25 studies with a total of 11,955 CRC patients met inclusion criteria. The rate of BRAFV600 was 10.8% (1288/11955). The BRAFV600E mutation in CRC was associated with advanced TNM stage, poor differentiation, mucinous histology, microsatellite instability (MSI), CpG island methylator phenotype (CIMP). This mutation was also associated with female gender, older age, proximal colon, and mutL homolog 1 (MLH1) methylation.
CONCLUSIONS
This meta-analysis demonstrated that BRAFV600E mutation was significantly correlated with adverse pathological features of CRC and distinct clinical characteristics. These data suggest that BRAFV600E mutation could be used to supplement standard clinical and pathological staging for the better management of individual CRC patients, and could be considered as a poor prognostic marker for CRC.
Topics: Colorectal Neoplasms; Genetic Association Studies; Genetic Markers; Humans; Mutation, Missense; Odds Ratio; Proto-Oncogene Mas; Proto-Oncogene Proteins B-raf
PubMed: 24594804
DOI: 10.1371/journal.pone.0090607