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Aging Sep 2023Hepatocellular Carcinoma (HCC) is one of the most common malignant cancers in humans and has a high fatality rate. In recent years, researchers have verified that the...
BACKGROUNDS
Hepatocellular Carcinoma (HCC) is one of the most common malignant cancers in humans and has a high fatality rate. In recent years, researchers have verified that the Wnt/β-catenin signaling pathway affects the clinicopathological features and prognosis of patients with HCC. Although many studies have investigated the relationship between Wnt/β-catenin signaling pathway and HCC, the prognostic value of β-catenin in HCC remains inconclusive. (Catenin Beta-1) is an important factor in the Wnt/β-catenin signaling pathway. However, no consensus has been reached on the clinical and prognostic significance of mutations in HCCs.
METHODS
Eligible studies and relevant data were obtained from PubMed, Web of Science, Elsevier, Cochrane Library, Ovid, and Embase databases. The correlation between mutations and clinical/prognosis of patients were evaluated. A fixed- or random-effects model was used to calculate pooled odds ratios (OR) and 95% confidence intervals (CI).
RESULTS
Seventeen studies matched the selection criteria, and 1828 patients were included. This meta-analysis demonstrated that patients with HCC with mutations had favorable clinicopathological features and survival. The combined ORs of 1-, 3- and 5-year overall survival were0.52 (n = 6 studies, 95% CI: 0.34-0.81, Z = 2.89, =0.004, 0.28 (n =6 studies, 95% CI: 0.18-0.42, Z = 6.03, <0.00001), -0.22 (n = 6 studies, 95% CI: 0.37-0.06, Z = 2.78, = 0.005), respectively. Additionally, mutation might be significantly associated with differentiation (OR = 0.54, 95% CI:0.36-0.81, Z = 2.98, = 0.003), TMN stages (Tumor, Node, Metastasis staging classification) (OR = -0.25, 95% CI:-0.33--0.18, Z = 6.60, <0.00001), liver cirrhosis (OR = 0.21, 95% CI:0.11-0.39, Z = 4.94, < = 0.00001), and HBV (Hepatitis B Virus) infection (OR = 0.44, 95% CI:0.31-0.64, Z = 4.37, <0.0001), but not with tumor size, metastasis, vascular invasion, and HCV infection.
CONCLUSIONS
mutation can serve as an indicator of favorable prognosis as well as a novel target for treatment in HCC.
PubMed: 37733676
DOI: 10.18632/aging.205047 -
Dermatologic Therapy Aug 2020The current systematic review aimed to evaluate the efficacy and safety of dabrafenib plus trametinib (dabrafenib-trametinib) with those of other therapeutic... (Review)
Review
Efficacy and safety of dabrafenib-trametinib in the treatment of unresectable or metastatic melanoma with BRAF V600 mutation: A systematic review and network meta-analysis.
The current systematic review aimed to evaluate the efficacy and safety of dabrafenib plus trametinib (dabrafenib-trametinib) with those of other therapeutic alternatives in the treatment of patients with BRAF V600 mutation unresectable or metastatic melanoma. The search was carried out on four databases up to July-2018. Two separate network meta-analyses (NMA) were performed using the frequentist method (random effects): one with an exclusive population with BRAF V600 mutation (NMA-pBRAFV600) and another with a mixed population (with or without the mutation: NMA-pMixed). An evidence profile was included using the GRADE method for NMA. The validity of the final estimator in the NMA-pMixed was assessed via sensitivity analysis. Five clinical trials were included in the NMA-pBRAFV600. In the NMA-pBRAFV600 population, dabrafenib-trametinib had a favorable effect on overall survival (OS) and progression-free survival (PFS) compared with dabrafenib, vemurafenib, and dacarbazine, and on partial response rate (PRR) and overall response rate (ORR) compared with dacarbazine and vemurafenib. In the NMA-pMixed population, dabrafenib-trametinib had a positive effect on OS vs ipilimumab 3 mg/kg and on PFS and PRR vs ipilimumab (3 and 10 mg/kg), nivolumab, and pembrolizumab. However, dabrafenib-trametinib, and vemurafenib-cobimetinib were comparable in terms of clinical efficacy. In addition, dabrafenib-trametinib was associated with less grades 3 and 4 adverse events.
PubMed: 32761749
DOI: 10.1111/dth.14135 -
Dermatologic Therapy Mar 2020The current systematic review aimed to evaluate and compare the efficacy and safety of dabrafenib-trametinib with those of other therapeutic alternatives in the... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of dabrafenib-trametinib in the treatment of unresectable advanced/metastatic melanoma with BRAF-V600 mutation: A systematic review and network meta-analysis.
The current systematic review aimed to evaluate and compare the efficacy and safety of dabrafenib-trametinib with those of other therapeutic alternatives in the treatment of patients with unresectable advanced/metastatic melanoma with BRAF-V600 mutation. The search was carried out on four databases up to July 2018. Two separate network meta-analyses (NMA) were performed using the frequentist method (random effects): one with an exclusive population with BRAF-V600 mutation (NMA-pBRAFV600) and another with mixed population (with or without the mutation: NMA-pMixed). An evidence profile was included using the GRADE method for NMA. The validity of the final estimator in the NMA-pMixed was assessed via a sensitivity analysis. Nine clinical trials were included in the NMA-pBRAFV600. Dabrafenib-trametinib was found to have a favorable effect on overall survival (OS) and progression-free survival (PFS) compared with dabrafenib, vemurafenib, and dacarbazine and on partial response rate (PRR) and overall response rate compared with dacarbazine and vemurafenib. In the NMA-pMixed, dabrafenib-trametinib was found to have a positive effect on OS versus ipilimumab 3 mg/kg and on PFS and PRR versus ipilimumab, nivolumab, and pembrolizumab. However, dabrafenib-trametinib and vemurafenib-cobimetinib significantly differed in terms of efficacy. In addition, dabrafenib-trametinib has a favorable effect on Grades 3 and 4 adverse events.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Imidazoles; Melanoma; Mutation; Network Meta-Analysis; Oximes; Proto-Oncogene Proteins B-raf; Pyridones; Pyrimidinones; Skin Neoplasms
PubMed: 31664762
DOI: 10.1111/dth.13145 -
International Journal of Surgery... Apr 2023Colorectal cancer (CRC) is the second most common cause of cancer-related death (9.4% of the 9.9 million cancer deaths). However, CRC develops slowly, and early...
BACKGROUND
Colorectal cancer (CRC) is the second most common cause of cancer-related death (9.4% of the 9.9 million cancer deaths). However, CRC develops slowly, and early detection and intervention can effectively improve the survival rate and quality of life. Although colonoscopy can detect and diagnose CRC, it is unsuitable for CRC screening in average-risk populations. Some commercial kits based on DNA mutation or methylation are approved for screening, but the low sensitivity for advanced adenoma or early-stage CRC would limit the applications.
MAIN RESULTS
Recently, researchers have focused on developing noninvasive or minimally invasive, easily accessible biomarkers with higher sensitivity and accuracy for CRC screening. Numerous reports describe advances in biomarkers, including DNA mutations and methylation, mRNA and miRNA, gut microbes, and metabolites, as well as low-throughput multiomics panels. In small cohorts, the specificity and sensitivity improved when fecal immunochemical testing combined with other biomarkers; further verification in large cohorts is expected. In addition, the continuous improvement of laboratory technology has also improved the sensitivity of detection technology, such as PCR, and the application of CRISPR/Cas technology. Besides, artificial intelligence has extensively promoted the mining of biomarkers. Machine learning was performed to construct a diagnosis model for CRC screening based on the cfDNA fragment features from whole-genome sequencing data. In another study, multiomics markers, including cfDNA, epigenetic, and protein signals, were also discovered by machine learning. Finally, advancements in sensor technology promote the applicability of volatile organic compounds in CRC early detection.
CONCLUSION
Here, the authors review advances in early detection and screening of CRC based on different biomarker types. Most studies reported optimistic findings based on preliminary research, and prospective clinical studies are ongoing. These promising biomarkers are expected to more accurately identify early-stage patients with CRC and be applied in the future.
Topics: Humans; Prospective Studies; Artificial Intelligence; Quality of Life; Biomarkers, Tumor; Early Detection of Cancer; DNA; Cell-Free Nucleic Acids; Colorectal Neoplasms
PubMed: 36974713
DOI: 10.1097/JS9.0000000000000260 -
Oral Surgery, Oral Medicine, Oral... Sep 2022This systematic review aimed to identify the molecular alterations of head and neck rhabdomyosarcomas (HNRMS) and their prognostic values. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This systematic review aimed to identify the molecular alterations of head and neck rhabdomyosarcomas (HNRMS) and their prognostic values.
STUDY DESIGN
An electronic search was performed using PubMed, Embase, Scopus, and Web of Science with a designed search strategy. Inclusion criteria comprised cases of primary HNRMS with an established histopathological diagnosis and molecular analysis. Forty-nine studies were included and were appraised for methodological quality using the Joanna Briggs Institute Critical Appraisal tools. Five studies were selected for meta-analysis.
RESULTS
HNRMS predominantly affects pediatric patients (44.4%), and the parameningeal region (57.7%) is the most common location. The alveolar variant (43.2%) predominates over the embryonal and spindle cell/sclerosing types, followed by the epithelioid and pleomorphic variants. PAX-FOXO1 fusion was observed in 103 cases of alveolar RMS (79.8%). MYOD1 mutation was found in 39 cases of sclerosing/spindle cell RMS (53.4%). FUS/EWSR1-TFCP2 gene fusions were identified in 21 cases of RMS with epithelioid and spindle cell morphologies (95.5%). The 5-year overall survival rate of patients was 61.3%, and MYOD1 mutation correlated with significantly higher mortality.
CONCLUSION
The genotypic profile of histologic variants of HNRMS is widely variable, and MYOD1 mutation could be a potential prognostic factor, but more studies are required to establish this.
Topics: Child; DNA-Binding Proteins; Humans; Mutation; Rhabdomyosarcoma; Transcription Factors
PubMed: 35840496
DOI: 10.1016/j.oooo.2021.12.128 -
BMC Cancer Feb 2018Although EGFR-TKI is the preferred treatment for NSCLC patients with sensitive mutations, subsequent drug resistance is almost inevitable. The specific mechanisms of... (Meta-Analysis)
Meta-Analysis Review
Frequency of the acquired resistant mutation T790 M in non-small cell lung cancer patients with active exon 19Del and exon 21 L858R: a systematic review and meta-analysis.
BACKGROUND
Although EGFR-TKI is the preferred treatment for NSCLC patients with sensitive mutations, subsequent drug resistance is almost inevitable. The specific mechanisms of EGFR-TKI drug resistance can be identified through repeat biopsy.
METHODS
To better understand the clinical characteristics of TKI resistance in NSCLC patients, we retrospectively reviewed studies of acquired TKI drug resistance using repeat biopsy from the last decade. The relevant literature was retrieved from January 2005 to August 2015 in the databases Medline and Embase. The search terms were NSCLC or non-small cell lung cancer and T790 M.
RESULTS
A total of 478 patients with NSCLC tested by repeated biopsy were confirmed to have acquired TKI resistance. Analysis indicated that 240 patients (50.21%) of the 478 patients with acquired TKI drug resistance had the T790 M mutation. The detection rate of T790 M in different repeat biopsy sites was also different, with the highest positive rate in the lymph nodes (60%) and the lowest detection rate in cerebrospinal fluid (less than 5%). In addition, patients with T790 M had longer overall survival compared to those without the mutation (P < 0.05). Of the 240 patients with T790 M mutations, 213 patients showed results consistent with the mutation analysis before TKI treatment, and the rate of patients with the L858R point mutation along with the T790 M mutation was lower than that of patients with the exon 19 deletion (36.42% to 58.30%).
CONCLUSIONS
T790 M occurred more frequently in patients with the exon 19 deletion than in those with exon 21 L858R, which gave the survival benefit of the T790 M mutation and may explain why patients with the exon 19 deletion had an improved overall survival.
Topics: Carcinoma, Non-Small-Cell Lung; Drug Resistance, Neoplasm; ErbB Receptors; Exons; Gene Frequency; Humans; Lung Neoplasms; Mutation; Protein Kinase Inhibitors; Survival Analysis
PubMed: 29409466
DOI: 10.1186/s12885-018-4075-5 -
Breast Cancer Research and Treatment Jul 2010Reports of BRCA genetic mutations and risk of death or recurrence are inconsistent. This study aimed to compare overall and disease-free breast cancer survival rates... (Meta-Analysis)
Meta-Analysis Review
Reports of BRCA genetic mutations and risk of death or recurrence are inconsistent. This study aimed to compare overall and disease-free breast cancer survival rates between BRCA1/2 mutation carriers and non-carriers for short-term and long-term outcomes separately. We searched the PUBMED and EMBASE databases and retrieved 452 articles using keywords that included breast cancer, BRCA mutation, and survival. Seventeen articles were selected for systematic review and among them 11 were included in our meta-analysis. We used the random-effects model to calculate the summary hazard ratio and corresponding 95% confidence interval. BRCA1 mutation carriers had significantly lower short-term and long-term overall survival rates (OSR) relative to non-carriers (HR = 1.92 [95% CI = 1.45-2.53]; 1.33 [1.12-1.58], respectively), while both short-term and long-term OSR of BRCA2 carriers did not differ from non-carriers (HR = 1.30 [95% CI = 0.95-1.76]; 1.12 [95% CI = 0.86-1.45], respectively). For short-term progression-free survival rate (PFSR), BRCA1 mutation carriers had a significantly lower rate than non-carriers (HR = 1.54 [95% CI = 1.12-2.12]), while BRCA2 mutation carriers had a similar PFSR (HR = 1.23 [95% CI = 0.96-1.58]). For long-term PFSRs, we found no significant results. Our results suggest that BRCA1 mutation decreases short-term and long-term OSRs and short-term PFSR, however, BRCA2 mutation does not affect either short-term or long-term survival rate, which is attributed to the different carcinogenic pathways for BRCA1 and BRCA2.
Topics: Breast Neoplasms; Disease-Free Survival; Female; Genes, BRCA1; Genes, BRCA2; Humans; Mutation; Proportional Hazards Models; Survival Rate; Time Factors
PubMed: 20376556
DOI: 10.1007/s10549-010-0859-2 -
Antibiotics (Basel, Switzerland) Aug 2021is now recognized as a commonly reported sexually transmitted pathogen, and the increasing drug resistance of has become a serious public health problem. The accuracy... (Review)
Review
BACKGROUND
is now recognized as a commonly reported sexually transmitted pathogen, and the increasing drug resistance of has become a serious public health problem. The accuracy of molecular detection for detecting moderate-level azithromycin resistance is not well-established. We summarized the data from studies of the 23S rRNA mutation at position 2611 with azithromycin resistance to determine the relationship between the mutation and resistance.
METHODS AND FINDINGS
In this systematic review and meta-analysis, two researchers independently searched six databases for studies with data for the azithromycin minimum inhibitory concentrations (MICs) and the 23S rRNA mutation C2611T of each isolate. Since the breakpoint of moderate-level resistance to azithromycin (ML-AzmR) was not determined, we divided the moderate level into two groups according to the range of MICs (moderate resistance limited to 2-128 mg/L or 4-128 mg/L) for data extraction. A random-effects model was used to calculate the pooled sensitivity rate, the specificity rate, the pooled positive likelihood ratio (PLR), the negative likelihood ratio (NLR), and the diagnostic odds ratio (DOR). Meta-regression analyses by detection method, isolates sampling (a random sample or not), location, and sample size were performed to explore the possible causes of heterogeneity. The potential publication bias of the included studies was conducted by the Deeks' test. We included 20 studies in our study: 20 studies have data of with MICs between 2 and 128 mg/L with mutation or without mutation at position 2611(4759 samples), and 14 studies have data of with MICs between 4 and 128 mg/L (3367 samples). In the group with the moderate level of 2-128 mg/L, the pooled sensitivity rate of the molecular assays was determined to be 71.9% (95% CI, 67.6-74%), the pooled specificity rate was 98.7% (95% CI, 98.2-99.0%), and the DOR ranged from 55.0 to 351.3 (mean, 139.1). In the 4-128 mg/L group, the pooled sensitivity rate was 91.9% (95% CI, 88.9-94.2%), the pooled specificity rate was 95.9% (95% CI, 95.1-96.6%), and the DOR ranged from 41.9 to 364.1 (mean, 123.6).
CONCLUSION
Through this meta-analysis, we found that the C2611T mutation of 23S rRNA is valuable for the molecular diagnostic of moderate-level azithromycin resistance (ML-AzmR) in , especially when the moderate level is set at 4-128 mg/L. This rapid molecular detection method can be used for the rapid identification of ML-AzmR isolates in the clinic.
PubMed: 34572609
DOI: 10.3390/antibiotics10091027 -
Infection and Drug Resistance 2019resistance to azithromycin has become a significant public health concern globally, and high-level azithromycin-resistant (HL-AzmR) isolates have emerged frequently.... (Review)
Review
BACKGROUND
resistance to azithromycin has become a significant public health concern globally, and high-level azithromycin-resistant (HL-AzmR) isolates have emerged frequently. However, high-level azithromycin resistance is considered to be caused by mutated alleles of 23S rRNA gene at position 2059, and identification of HL-AzmR isolates mainly relies on agar dilution method or E-test method. This study aimed to assess the accuracy of the molecular assays targeting the mutation A2059G for identifying HL-AzmR isolates and thereby determine the association between the mutation and high-level azithromycin resistance.
METHODS
Two researchers independently searched six databases to identify studies published from the launch of each database to October 15, 2017. The fixed effects model was used to estimate the pooled sensitivity rate, specificity rate, positive predictive value (PPV), and negative predictive value (NPV). Summary receiver operating characteristic curves were generated, and the area under the curve (AUC) was determined to estimate the overall performance of the assays. The Deeks' test was conducted to evaluate potential publication bias.
RESULTS
Ten relevant studies were included in the meta-analysis to assess the synthetic accuracy of the molecular assays. The molecular assays had the synthetic sensitivity rate of 97.8% and the synthetic specificity rate of 99.1%. And the aggregated PPV and NPV were 96.4% and 99.5%, respectively. AUC was 0.99, suggesting a close relation existing between the mutation A2059G and high-level azithromycin resistance. This indicated that the molecular assays targeting the mutation A2059G have relatively high overall accuracy for identifying HL-AzmR isolates. Publication bias was statistically significant.
CONCLUSION
The mutation A2059G is the critical factor causing high-level azithromycin resistance. Hence, molecular methods are recommended to be put into clinical practice by commercialization, which will assist clinicians to prescribe more precisely.
PubMed: 30643437
DOI: 10.2147/IDR.S183754 -
Surgical Oncology Jun 2018Hepatic resection is considered the optimal potentially curative treatment for colorectal liver metastases (CRLM). Following resection, up to two-thirds of patients will... (Review)
Review
Clinical significance and prognostic relevance of KRAS, BRAF, PI3K and TP53 genetic mutation analysis for resectable and unresectable colorectal liver metastases: A systematic review of the current evidence.
BACKGROUND
Hepatic resection is considered the optimal potentially curative treatment for colorectal liver metastases (CRLM). Following resection, up to two-thirds of patients will develop recurrence within 5-years. Genetic mutation analysis of CRLM, especially KRAS status, has been proposed as a means to guide treatment, as well as identifying patients who can derive the most survival benefit from hepatic resection.
METHODS
A systematic review of the literature was conducted the PubMed, Embase and Cochrane library through February 8th, 2018. The following algorithm was applied: "(colorectal OR rectal OR colon OR colonic) AND (liver OR hepatic) AND (metastasis OR metastases) AND (gene OR mutation OR KRAS OR BRAF OR SMAD4 OR RAS OR TP53 OR P53 OR APC OR PI3K OR MSI OR EGFR OR MACC1 OR microsatellite)."
RESULTS
From the 2404 records retrieved, 78 studies were finally deemed eligible; 47 studies reported mutational data on patients with resectable CRLM, whereas 31 studies reported on patients with unresectable CRLM. Mutational analyses were mostly performed on the CRLM specimen rather than the primary CRC. The vast majority of studies reported on the KRAS mutational status (88.5%, n = 69/78). Prevalence of KRAS mutations ranged from 25% to 52%. Most studies reported that RAS mutation was a negative prognostic factor for overall (OS) (n = 24) and recurrence-free (RFS) (n = 9) survival; a few reports noted no effect of RAS mutational status on OS (n = 4) or RFS (n = 6). Twelve studies reported on BRAF mutations with a prevalence of BRAF mutation ranging from 0 to 9.1% in resected CRLM specimens. BRAF mutation was strongly associated with a worse prognosis. TP53 and PIK3CA gene mutations did not affect long-term outcomes.
CONCLUSIONS
The biological status of each tumor provides the basis for individualized cancer therapeutics. Data on the mutational status on CRLM should be a part of multidisciplinary discussions to help inform the therapeutic approach, type of chemotherapy, as well as timing and approach of surgical resection.
Topics: Biomarkers, Tumor; Colorectal Neoplasms; Hepatectomy; Humans; Liver Neoplasms; Mutation; Phosphatidylinositol 3-Kinases; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras); Survival Rate; Tumor Suppressor Protein p53
PubMed: 29937183
DOI: 10.1016/j.suronc.2018.05.012