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BMC Gastroenterology Jul 2021Approximately 5.0-24.2% of colorectal cancers (CRCs) have inactivating mutations in SMAD4, making it one of the frequently mutated genes in CRC. We thus carried out a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Approximately 5.0-24.2% of colorectal cancers (CRCs) have inactivating mutations in SMAD4, making it one of the frequently mutated genes in CRC. We thus carried out a comprehensive system review and meta-analysis investigating the prognostic significance and clinicopathological features of SMAD4 gene mutation in CRC patients.
METHODS
A detailed literature search was conducted in PubMed, Web of Science and Embase databases to study the relationship between SMAD4 mutations and the demographic and clinicopathological characteristics in CRC patients. The hazard ratios (HRs) with 95% confidence intervals (CI) were used to evaluate the effect of SMAD4 mutations on overall survival (OS) and progression-free survival (PFS)/recurrence-free survival (RFS).
RESULTS
Ten studies enrolling 4394 patients were eligible for inclusion. Data on OS were available from 5 studies and data on PFS/RFS were available from 3 studies. Comparing SMAD4-mutated CRC patients with SMAD4 wild-type CRC patients, the summary HR for OS was 1.46 (95% CI 1.28-1.67, P = 0.001), the summary HR for PFS/RFS was 1.59 (95% CI 1.14-2.22, P = 0.006). In terms of clinicopathology parameters, 9 studies have data that can be extracted, SMAD4 mutations were associated with tumor location (odds ratio [OR] = 1.15, colon/rectum, 95% CI 1.01-1.31, P = 0.042), TNM stage (OR = 1.28, stage IV/I-III, 95% CI 1.03-1.58, P = 0.025), lymph node metastasis (OR = 1.42, N1 + N2/N0, 95% CI 1.20-1.67, P < 0.001), mucinous differentiation (OR = 2.23, 95% CI 1.85-2.70, P < 0.001) and rat sarcoma viral oncogene homolog (RAS) mutation status (OR = 2.13, 95% CI 1.37-3.34, P = 0.001). No connection was found with age, gender, tumor grade, microsatellite instability status and b-viral oncogene homolog B1 mutation status. Besides, publication bias was not observed in any study.
CONCLUSIONS
This meta-analysis suggests that SMAD4 mutation was associated with OS, PFS/RFS, and clinicopathological parameters, including tumor site, disease stage, RAS status, lymph node metastasis and mucinous differentiation. Our meta-analysis indicated that SMAD4 mutations could predict the poor prognosis and aggressive clinicopathological characteristics of CRC. More large-sample cohort studies are needed to confirm this conclusion. Since SMAD4 mutations are closely related to RAS mutations, their relationship warrants further investigation.
Topics: Biomarkers, Tumor; Colorectal Neoplasms; Humans; Microsatellite Instability; Mutation; Prognosis; Smad4 Protein
PubMed: 34301194
DOI: 10.1186/s12876-021-01864-9 -
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 -
American Journal of Transplantation :... Mar 2023Solid organ transplantation (SOT) recipients are known to carry an increased risk of malignancy because of long-term immunosuppression. However, the progression of...
Solid organ transplantation (SOT) recipients are known to carry an increased risk of malignancy because of long-term immunosuppression. However, the progression of intraductal papillary mucinous neoplasm of the pancreas (IPMN) in this population remains unclear. We performed a systematic review by searching PubMed, Embase, Scopus, and Google Scholar. All studies containing IPMNs in solid organ transplantation recipients were screened. We included 11 studies in our final analysis, totaling 274 patients with IPMNs of the 8213 SOT recipients. The prevalence from 8 studies was 4.7% (95% CI 2.4%-7.7%) in a random-effects model with median study periods of 24 to 220 months. The median rate for all progressions from 10 studies was 20% (range, 0%-88%) within 13 to 41 months of the median follow-up time. By utilizing the results of 3 case-control studies, the relative risk from a random-effects model for progression (worrisome features and high-risk stigmata) of IPMNs was 0.39 (95% CI 0.12-1.31). No adenocarcinoma derived from IPMN was reported in the included studies. Overall, this study indicates that the progression of pretransplant IPMN does not increase drastically compared with the general nontransplant population. However, considering the limited literature, further studies are required for confirmation.
Topics: Humans; Pancreatic Intraductal Neoplasms; Carcinoma, Pancreatic Ductal; Prevalence; Retrospective Studies; Adenocarcinoma, Mucinous; Pancreatic Neoplasms; Pancreas; Organ Transplantation
PubMed: 36695699
DOI: 10.1016/j.ajt.2022.11.024 -
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 -
European Journal of Radiology Open Dec 2023Intraductal papillary mucinous neoplasm of the bile ducts (IPMN-B) is a true pre-cancerous lesion, which shares common features with pancreatic IPMN (IPMN-P). While... (Review)
Review
RATIONALE AND OBJECTIVES
Intraductal papillary mucinous neoplasm of the bile ducts (IPMN-B) is a true pre-cancerous lesion, which shares common features with pancreatic IPMN (IPMN-P). While IPMN-P is a well described entity for which guidelines were formulated and revised, IPMN-B is a poorly described entity.We carried out a systematic review to evaluate the existing literature, emphasizing the role of MRI in IPMN-B depiction.
MATERIALS AND METHODS
PubMed database was used to identify original studies and case series that reported MR Imaging features of IPMN-B. The search keywords were "IPMN OR intraductal papillary mucinous neoplasm OR IPNB OR intraductal papillary neoplasm of the bile duct AND Biliary OR biliary cancer OR hepatic cystic lesions". Risk of bias and applicability were evaluated using the QUADAS-2 tool.
RESULTS
884 Records were Identified through database searching. 12 studies satisfied the inclusion criteria, resulting in MR features of 288 patients. All the studies were retrospective. Classic features of IPMN-B are under-described. Few studies note worrisome features, concerning for an underlying malignancy. 50 % of the studies had a high risk of bias and concerns regarding applicability.
CONCLUSIONS
The MRI features of IPMN-B are not well elaborated and need to be further studied. Worrisome features and guidelines regarding reporting the imaging findings should be established and published. Radiologists should be aware of IPMN-B, since malignancy diagnosis in an early stage will yield improved prognosis.
PubMed: 37609049
DOI: 10.1016/j.ejro.2023.100515 -
Gynecologic Oncology Aug 2019There is a need to develop and validate biomarkers for treatment response and survival in tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
There is a need to develop and validate biomarkers for treatment response and survival in tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response after neoadjuvant chemotherapy (NACT). Our aim was to review current evidence to determine whether the CRS is prognostic in women with tubo-ovarian HGSC treated with NACT.
METHODS
We established an international collaboration to conduct a systematic review and meta-analysis, pooling individual patient data from 16 sites in 11 countries. Patients had stage IIIC/IV HGSC, 3-4 NACT cycles and >6-months follow-up. Random effects models were used to derive combined odds ratios in the pooled population to investigate associations between CRS and progression free and overall survival (PFS and OS).
RESULTS
877 patients were included from published and unpublished studies. Median PFS and OS were 15 months (IQR 5-65) and 28 months (IQR 7-92) respectively. CRS3 was seen in 249 patients (28%). The pooled hazard ratios (HR) for PFS and OS for CRS3 versus CRS1/CRS2 were 0·55 (95% CI, 0·45-0·66; P < 0·001) and 0·65 (95% CI 0·50-0·85, P = 0·002) respectively; no heterogeneity was identified (PFS: Q = 6·42, P = 0·698, I2 = 0·0%; OS: Q = 6·89, P = 0·648, I2 = 0·0%). CRS was significantly associated with PFS and OS in multivariate models adjusting for age and stage. Of 306 patients with known germline BRCA1/2 status, those with BRCA1/2 mutations (n = 80) were more likely to achieve CRS3 (P = 0·027).
CONCLUSIONS
CRS3 was significantly associated with improved PFS and OS compared to CRS1/2. This validation of CRS in a real-world setting demonstrates it to be a robust and reproducible biomarker with potential to be incorporated into therapeutic decision-making and clinical trial design.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carboplatin; Disease-Free Survival; Fallopian Tube Neoplasms; Female; Humans; Neoadjuvant Therapy; Neoplasms, Cystic, Mucinous, and Serous; Ovarian Neoplasms; Treatment Outcome
PubMed: 31118141
DOI: 10.1016/j.ygyno.2019.04.679 -
Frontiers in Oncology 2021To assess the diagnostic accuracy of diffusion-weighted imaging (DWI) in predicting the malignant potential in patients with intraductal papillary mucinous neoplasms...
Diagnostic Performance of Diffusion-Weighted Imaging for Differentiating Malignant From Benign Intraductal Papillary Mucinous Neoplasms of the Pancreas: A Systematic Review and Meta-Analysis.
OBJECTIVES
To assess the diagnostic accuracy of diffusion-weighted imaging (DWI) in predicting the malignant potential in patients with intraductal papillary mucinous neoplasms (IPMNs) of the pancreas.
METHODS
A systematic search of articles investigating the diagnostic performance of DWI for prediction of malignant potential in IPMNs was conducted from PubMed, Embase, and Web of Science from January 1997 to 10 February 2020. QUADAS-2 tool was used to evaluate the study quality. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratios (PLR), negative likelihood ratios (NLR), and their 95% confidence intervals (CIs) were calculated. The summary receiver operating characteristic (SROC) curve was then plotted, and meta-regression was also performed to explore the heterogeneity.
RESULTS
Five articles with 307 patients were included. The pooled sensitivity and specificity of DWI were 0.74 (95% CI: 0.65, 0.82) and 0.94 (95% CI: 0.78, 0.99), in evaluating the malignant potential of IPMNs. The PLR was 13.5 (95% CI: 3.1, 58.7), the NLR was 0.27 (95% CI: 0.20, 0.37), and DOR was 50.0 (95% CI: 11.0, 224.0). The area under the curve (AUC) of SROC curve was 0.84 (95% CI: 0.80, 0.87). The meta-regression showed that the slice thickness of DWI (p = 0.02) and DWI parameter (p= 0.01) were significant factors affecting the heterogeneity.
CONCLUSIONS
DWI is an effective modality for the differential diagnosis between benign and malignant IPMNs. The slice thickness of DWI and DWI parameter were the main factors influencing diagnostic specificity.
PubMed: 34290974
DOI: 10.3389/fonc.2021.637681 -
International Journal of Gynecological... Jul 2017Immunohistochemistry is widely used to support a pathology diagnosis of cervical adenocarcinoma despite the absence of a systematic review and meta-analysis of the... (Meta-Analysis)
Meta-Analysis Review
Tissue-based Immunohistochemical Biomarker Accuracy in the Diagnosis of Malignant Glandular Lesions of the Uterine Cervix: A Systematic Review of the Literature and Meta-Analysis.
Immunohistochemistry is widely used to support a pathology diagnosis of cervical adenocarcinoma despite the absence of a systematic review and meta-analysis of the published data. This systematic review and meta-analysis was performed to investigate the sensitivity and specificity of immunohistochemistry biomarkers in the tissue-based diagnosis of cervical adenocarcinoma histotypes compared with normal endocervix and benign glandular lesions. The systematic review and meta-analysis used a PICOT framework and QUADAS-2 to evaluate the quality of included studies. The literature search spanned 40 years and ended June 30, 2015. Abstracts of identified records were independently screened by 2 of the authors who then conducted a full-text review of selected articles. Sensitivity and specificity of immunohistochemistry expression in malignant glandular lesions of the cervix classified per WHO 2003 compared with 5 benign comparators (normal/benign endocervix, and benign endocervical, endometrioid, gastric, and mesonephric lesions) were calculated. Of 902 abstracts screened, 154 articles were selected for full review. Twenty-five articles with results for 36 biomarkers were included. The only biomarker with enough studies for a meta-analysis was p16 and the definition of positive p16 staining among them was variable. Nevertheless, any positive p16 expression was sensitive, ranging from 0.94 to 0.98 with narrow confidence intervals (CIs), for adenocarcinoma in situ (AIS) and mucinous adenocarcinomas in comparison with normal/benign endocervix and benign endocervical and endometrioid lesions. Specificity for AIS and mucinous adenocarcinomas was also high with narrow CIs compared with benign endocervical lesions. The specificity was high for AIS, 0.99 (0.24, 1.0), and mucinous adenocarcinoma, 0.95 (0.52, 1.0), compared with normal/benign endocervix but with wider CIs, and low with very wide CIs compared with benign endometrioid lesions: 0.31 (0.00, 0.99) and 0.34 (0.00, 0.99), respectively. Results from single studies showed that p16, p16/Ki67 dual stain, ProExC, CEA, ESA, HIK1083, Claudin 18, and ER loss in perilesional stromal cells were useful with high (≥0.75) sensitivity and specificity estimates in ≥1 malignant versus benign comparisons. None of the biomarkers had highly useful sensitivity and specificity estimates for AIS, mucinous adenocarcinomas, or minimal deviation adenocarcinoma/gastric adenocarcinoma compared with benign gastric or mesonephric lesions or for mesonephric carcinoma compared with normal/benign endocervix, benign endocervical, endometrial, or mesonephric lesions. Any expression of p16 supports a diagnosis of AIS and mucinous adenocarcinomas in comparison with normal/benign endocervix and benign endocervical lesions. The majority of studies did not separate mosaic/focal p16 staining from diffuse staining as a distinct pattern of p16 overexpression and this may have contributed to the poor performance of p16 in distinguishing AIS and mucinous adenocarcinomas from benign endometrioid lesions. Single studies support further investigation of 8 additional biomarkers that have highly useful sensitivity and specificity estimates for ≥1 malignant glandular lesions compared with ≥1 of the 5 benign comparators.
Topics: Adenocarcinoma; Adenocarcinoma in Situ; Adenocarcinoma, Mucinous; Biomarkers, Tumor; Cervix Uteri; Cyclin-Dependent Kinase Inhibitor p16; Female; Humans; Immunohistochemistry; Ki-67 Antigen; Sensitivity and Specificity; Uterine Cervical Neoplasms
PubMed: 27801764
DOI: 10.1097/PGP.0000000000000345 -
World Journal of Gastroenterology Jul 2015To analyze the benefits and harms of pancreatic cancer screening in familial high-risk individuals (HRIs). (Review)
Review
AIM
To analyze the benefits and harms of pancreatic cancer screening in familial high-risk individuals (HRIs).
METHODS
Studies were identified by searching PubMed, EBSCO, ClinicalTrials.gov and the Cochrane database from database inception to June 2014. We also obtained papers from the reference lists of pertinent studies and systematic reviews. English-language trials and observational studies were searched. The key words used as search terms were "screening" and "surveillance". Cost-effectiveness, diagnostic rate, survival rate, mortality and adverse events were the outcomes of interest. Age, sex, lifestyle and other confounding factors were also considered. However, anticipating only a few of these studies, we also included observational studies with or without control groups. We also included studies concerning the anxiety associated with pancreatic cancer risk and other psychological changes in familial HRIs. We extracted details on study design, objectives, population characteristics, inclusion criteria, year of enrollment, method of screening, adjusted and unadjusted mortality, cost-effectiveness and adverse events from the included studies. Studies were assessed using the Reporting of Observational studies in Epidemiology (STROBE) checklist.
RESULTS
Sixteen studies on pancreatic cancer screening were included. Five studies included control groups, nine were observational studies without control groups, and the other two studies investigated the worry associated with pancreatic cancer risk. We found that pancreatic cancer screening resulted in a high curative resection rate (60% vs 25%, P = 0.011), longer median survival time (14.5 mo vs 4 mo, P < 0.001), and higher 3-year survival rate (20% vs 15.0%, P = 0.624). We also found that familial HRIs had a higher diagnostic rate of pancreatic tumors than controls (34% vs 7.2%, P < 0.001). In patients who underwent regular physical examinations, more stage I pancreatic cancers were observed (19% vs 2.6%, P = 0.001). In addition, endoscopic ultrasonography, which was the main means of detection, diagnosed 64.3% of pancreatic cancers. In comparison, endoscopic retrograde cannulation of the pancreas, magnetic resonance imaging, and computed tomography diagnosed 28.6%, 42.9%, and 21.4%, respectively. For mass lesions, instant surgery was recommended because of the beneficial effects of post-operative chemotherapy. However, in patients with intraductal papillary mucinous neoplasms, we did not find a significant difference in outcome between surgery and follow-up without treatment. Moreover, pancreatic cancer screening in familial HRIs had a greater perceived risk of pancreatic cancer (P < 0.0001), higher levels of anxiety regarding pancreatic cancer (P < 0.0001), and increased economic burden.
CONCLUSION
Pancreatic cancer screening in familial HRIs is associated with a higher detection rate and longer survival, although screening may influence psychological function and increase the economic burden.
Topics: Biomarkers, Tumor; Diagnostic Imaging; Early Detection of Cancer; Genetic Predisposition to Disease; Genetic Testing; Heredity; Humans; Neoplasm Staging; Pancreatic Neoplasms; Pedigree; Phenotype; Predictive Value of Tests; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome
PubMed: 26229410
DOI: 10.3748/wjg.v21.i28.8678 -
Frontiers in Immunology 2022Mammalian neuraminidases (NEUs), also known as sialidases, are enzymes that cleave off the terminal neuraminic, or sialic, acid resides from the carbohydrate moieties of...
Mammalian neuraminidases (NEUs), also known as sialidases, are enzymes that cleave off the terminal neuraminic, or sialic, acid resides from the carbohydrate moieties of glycolipids and glycoproteins. A rapidly growing body of literature indicates that in addition to their metabolic functions, NEUs also regulate the activity of their glycoprotein targets. The simple post-translational modification of NEU protein targets-removal of the highly electronegative sialic acid-affects protein folding, alters protein interactions with their ligands, and exposes or covers proteolytic sites. Through such effects, NEUs regulate the downstream processes in which their glycoprotein targets participate. A major target of desialylation by NEUs are mucins (MUCs), and such post-translational modification contributes to regulation of disease processes. In this review, we focus on the regulatory roles of NEU-modified MUCs as coordinators of disease pathogenesis in fibrotic, inflammatory, infectious, and autoimmune diseases. Special attention is placed on the most abundant and best studied NEU1, and its recently discovered important target, mucin-1 (MUC1). The role of the NEU1 - MUC1 axis in disease pathogenesis is discussed, along with regulatory contributions from other MUCs and other pathophysiologically important NEU targets.
Topics: Animals; Glycoproteins; Immune System Diseases; Mammals; Mucins; N-Acetylneuraminic Acid; Neuraminidase
PubMed: 35479093
DOI: 10.3389/fimmu.2022.883079