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Technology in Cancer Research &... 2022Cyclin D1 has been identified as a proto-oncogene associated with the uncontrolled proliferation of tumor cells. This systematic review and meta-analysis aims to... (Meta-Analysis)
Meta-Analysis
Cyclin D1 has been identified as a proto-oncogene associated with the uncontrolled proliferation of tumor cells. This systematic review and meta-analysis aims to estimate the prognostic significance of cyclin D1 in multiple myeloma (MM) patients. We searched for qualified data in PubMed, Embase, and Web of Science up to February 2020. Data quality was assessed by the Newcastle-Ottawa scale (NOS). Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were used to evaluate the relationship between cyclin D1 expression and overall survival (OS), progression-free survival (PFS)/event-free survival (EFS) in patients with MM. A total of 13 studies involving 961 patients were included. Overall, pooled analysis revealed significant heterogeneity between cyclin D1 expression and the prognosis of MM (OS, HR = 1.08, 95% CI: 0.71-1.64, = 67.9%; PFS/EFS, HR = 0.97, 95% CI: 0.49-1.93, = 85.8%). Subgroup analysis revealed that the prolongation of OS was relevant to increased expression of cyclin D1 in MM patients in the relapsed and refractory group (OS, HR = 0.46, 95% CI: 0.24-0.90). Another subgroup assessment of OS established that MM patients with overexpression in the bortezomib group had longer survival time (HR = 0.30, 95% CI: 0.11-0.82), whereas, those overexpressing in the conventional chemotherapy group had poor prognosis (HR = 2.19, 95% CI: 1.18-4.08). We also found that increased cyclin D1 expression correlated favorably with PFS in the autologous stem cell transplantation (ASCT) (HR = 0.45, 95% CI: 0.28-0.73) or reverse transcription-polymerase chain reaction (RT-PCR) group (HR = 0.41, 95% CI: 0.26-0.64). The result of this meta-analysis suggested that overexpression might be a predictive biomarker for MM patients when treated with bortezomib, receiving ASCT, or in relapsed and refractory period.
Topics: Biomarkers, Tumor; Cyclin D1; Gene Expression Regulation, Neoplastic; Humans; Immunohistochemistry; Multiple Myeloma; Polymerase Chain Reaction; Prognosis; Publication Bias; Survival Analysis
PubMed: 35098809
DOI: 10.1177/15330338211065252 -
PloS One 2022Early-life adversity (ELA) causes long-lasting structural and functional changes to the brain, rendering affected individuals vulnerable to the development of... (Meta-Analysis)
Meta-Analysis
Early-life adversity (ELA) causes long-lasting structural and functional changes to the brain, rendering affected individuals vulnerable to the development of psychopathologies later in life. Immediate-early genes (IEGs) provide a potential marker for the observed alterations, bridging the gap between activity-regulated transcription and long-lasting effects on brain structure and function. Several heterogeneous studies have used IEGs to identify differences in cellular activity after ELA; systematically investigating the literature is therefore crucial for comprehensive conclusions. Here, we performed a systematic review on 39 pre-clinical studies in rodents to study the effects of ELA (alteration of maternal care) on IEG expression. Females and IEGs other than cFos were investigated in only a handful of publications. We meta-analyzed publications investigating specifically cFos expression. ELA increased cFos expression after an acute stressor only if the animals (control and ELA) had experienced additional hits. At rest, ELA increased cFos expression irrespective of other life events, suggesting that ELA creates a phenotype similar to naïve, acutely stressed animals. We present a conceptual theoretical framework to interpret the unexpected results. Overall, ELA likely alters IEG expression across the brain, especially in interaction with other negative life events. The present review highlights current knowledge gaps and provides guidance to aid the design of future studies.
Topics: Animals; Brain; Cytoskeletal Proteins; Early Growth Response Protein 1; Gene Expression; Genes, Immediate-Early; Male; Nerve Tissue Proteins; Proto-Oncogene Proteins c-fos; Rodentia; Stress, Psychological
PubMed: 35025862
DOI: 10.1371/journal.pone.0253406 -
JPMA. the Journal of the Pakistan... Oct 2021To focus mainly on the role of proto-oncogene Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-Ras) and tumour-suppressor gene p53 which are among the most commonly...
OBJECTIVE
To focus mainly on the role of proto-oncogene Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-Ras) and tumour-suppressor gene p53 which are among the most commonly mutated genes in biliary tract carcinomas.
METHODS
The systematic review comprised research articles published between 2002 and 2019 on PubMed and Google Scholar databases which were searched using the terms 'TP53', 'K-Ras', 'mutation', 'biliary tract carcinoma', 'cholangiocarcinoma', and 'murine model'. Repetitions, duplicates and irrelevant articles were excluded. No data was retrieved from posters, presentations and symposiums, and experiments involving bile aspirations were also excluded.
RESULTS
Of the 72 articles reviewed, 11(15.3%) were included. Of them, 3(27.3%) studies, conducted in China, Japan and Taiwan, reported a positive correlation between K-Ras mutation and biliary tract carcinoma. Only 1(9%) study, conducted in China, showed the sole correlation between p53 inactivation and biliary tract carcinoma. Also, 4(36.4%) studies, conducted in China, Japan and Europe, showed a positive association of both K-Ras mutation and p53 inactivation with biliary tract carcinoma.
CONCLUSIONS
K-Ras and p53 mutation both contribute to biliary tract carcinoma. K-Ras mutation, however, has a much higher frequency compared to p53 inactivation in such cancers.
Topics: Animals; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Genes, ras; Mice; Mutation; Polymerase Chain Reaction; Tumor Suppressor Protein p53
PubMed: 34974575
DOI: 10.47391/JPMA.11-1322 -
Medicine Dec 2021Testing of B-Raf proto-oncogene (BRAF) mutation in tumor is necessary before targeted therapies are given. When tumor samples are not available, plasma samples are... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Testing of B-Raf proto-oncogene (BRAF) mutation in tumor is necessary before targeted therapies are given. When tumor samples are not available, plasma samples are commonly used for the testing of BRAF mutation. The aim of this study was to investigate the diagnostic accuracy of BRAF mutation testing using plasma sample of cancer patients.
METHODS
Databases of Pubmed, Embase, and Cochrane Library were searched for eligible studies investigating BRAF mutation in paired tissue and plasma samples of cancer patients. A total of 798 publications were identified after database searching. After removing 229 duplicated publications, 569 studies were screened using the following exclusion criteria: (1) BRAF mutation not measured in plasma or in tumor sample; (2) lacking BRAF-wildtype or BRAF-mutated samples; (3) tissue and plasma samples not paired; (4) lacking tumor or plasma samples; (5) not plasma sample; (6) not cancer; (7) un-interpretable data. Accuracy data and relevant information were extracted from each eligible study by 2 independent researchers and analyzed using statistical software.
RESULTS
After pooling the accuracy data from 3943 patients of the 53 eligible studies, the pooled sensitivity, specificity, and diagnostic odds ratio of BRAF mutation testing using plasma sample were 69%, 98%, and 55.78, respectively. Area under curve of summary receiver operating characteristic curve was 0.9435. Subgroup analysis indicated that BRAF mutation testing using plasma had overall higher accuracy (diagnostic odds ratio of 89.17) in colorectal cancer, compared to melanoma and thyroid carcinoma. In addition, next-generation sequencing had an overall higher accuracy in detecting BRAF mutation using plasma sample (diagnostic odds ratio of 63.90), compared to digital polymerase chain reaction (PCR) and conventional PCR, while digital PCR showed the highest sensitivity (74%) among the 3 techniques.
CONCLUSION
BRAF testing using plasma sample showed an overall high accuracy compared to paired tumor tissue sample, which could be used for cancer genotyping when tissue sample is not available. Large prospective studies are needed to further investigate the accuracy of BRAF mutation testing in plasma sample.
Topics: DNA Mutational Analysis; Humans; Mutation; Proto-Oncogene Proteins B-raf; Reproducibility of Results; Sensitivity and Specificity
PubMed: 34941166
DOI: 10.1097/MD.0000000000028382 -
Journal of Diabetes Investigation Mar 2022Type 2 diabetes is known as a risk factor for pancreatic cancer (PC). Various genetic and environmental factors cause both these global chronic diseases. The mechanisms... (Review)
Review
Type 2 diabetes is known as a risk factor for pancreatic cancer (PC). Various genetic and environmental factors cause both these global chronic diseases. The mechanisms that define their relationships are complex and poorly understood. Recent studies have implicated that metabolic abnormalities, including hyperglycemia and hyperinsulinemia, could lead to cell damage responses, cell transformation, and increased cancer risk. Hence, these kinds of abnormalities following molecular events could be essential to develop our understanding of this complicated link. Among different molecular events, focusing on shared signaling pathways including metabolic (PI3K/Akt/mTOR) and mitogenic (MAPK) pathways in addition to regulatory mechanisms of gene expression such as those involved in non-coding RNAs (miRNAs, circRNAs, and lncRNAs) could be considered as powerful tools to describe this association. A better understanding of the molecular mechanisms involved in the development of type 2 diabetes and pancreatic cancer would help us to find a new research area for developing therapeutic and preventive strategies. For this purpose, in this review, we focused on the shared molecular events resulting in type 2 diabetes and pancreatic cancer. First, a comprehensive literature review was performed to determine similar molecular pathways and non-coding RNAs; then, the final results were discussed in more detail.
Topics: Animals; Diabetes Mellitus, Type 2; Humans; MAP Kinase Signaling System; MicroRNAs; Pancreatic Neoplasms; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; RNA, Long Noncoding; TOR Serine-Threonine Kinases
PubMed: 34859606
DOI: 10.1111/jdi.13727 -
Critical Reviews in Oncology/hematology Jan 2022This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis evaluated the prognostic role of cell-free DNA (cfDNA) in pancreatic ductal adenocarcinoma (PDAC). Eligible studies reported differences in overall (OS) and progression-free survival (PFS) by cfDNA status. The random effect model yielded the pooled hazard ratios (HRs) and 95 % confidence intervals (CI). Detection of circulant-tumor DNA (ctDNA), KRAS mutations and other cfDNA alterations constitute detectable cfDNA biomarkers. Altogether, 38 studies (3,318 patients) were eligible. Progression-free and overall survival were decreased with detectable ctDNA (HR = 1.92, 95 %CI:(1.29,2.86); HR = 2.25, 95 %CI:(1.73,2.92)) and KRAS mutations (HR = 1.88, CI:1.22,2.92,); HR = 1.52, 95 %CI:(1.22,1.90)) respectively, across various stages. In unresectable cases, ctDNA (HR = 2.50, 95 %CI:(1.94,3.23)), but not KRAS mutations (HR = 1.16, 95 %CI:(0.46,2.94)) signaled risk for progression. Detectable cfDNA biomarkers correlated with worse prognosis in resectable cases and if detected during treatment. In conclusion, cfDNA biomarkers indicate accelerated progression and decreased survival in PDAC. Significance of KRAS mutations detection in unresectable cases is to be determined.
Topics: Adenocarcinoma; Biomarkers, Tumor; Cell-Free Nucleic Acids; DNA, Neoplasm; Humans; Mutation; Pancreatic Neoplasms; Prognosis; Proto-Oncogene Proteins p21(ras)
PubMed: 34843928
DOI: 10.1016/j.critrevonc.2021.103548 -
Neuro-oncology Apr 2022Detailed prevalence estimates of BRAFV600 mutations and BRAF inhibitor (BRAFi) treatment responses in V600-mutant glioma will inform trial development.
BACKGROUND
Detailed prevalence estimates of BRAFV600 mutations and BRAF inhibitor (BRAFi) treatment responses in V600-mutant glioma will inform trial development.
METHODS
Our systematic review analyzed overall prevalence of BRAFV600 mutations in glioma and BRAFi treatment response.
RESULTS
Based on 13 682 patients in 182 publications, the prevalence of BRAFV600 in epithelioid glioblastoma (eGBM) was 69% [95% CI: 45-89%]; pleomorphic xanthoastrocytoma (PXA): 56% [48-64%] anaplastic pleomorphic xanthoastrocytoma (aPXA): 38% [23-54%], ganglioglioma (GG): 40% [33-46%], and anaplastic ganglioglioma (aGG): 46% [18-76%]. Prevalence in astroblastoma was 24% [8-43%], desmoplastic infantile astrocytoma (DIA): 16% [0-57%], subependymal giant cell astrocytoma (SEGA): 8% [0-37%], dysembryoplastic neuroepithelial tumor (DNET): 3% [0-11%], diffuse astrocytoma (DA): 3% [0-9%], and pilocytic astrocytoma (PA): 3% [2-5%]. We reviewed 394 V600-mutant gliomas treated with BRAFi from 130 publications. One hundred and twenty-nine pediatric low-grade gliomas showed 4 (3.1%) complete response (CR); 53 (41.1%) partial response (PR); 64 (49.6%) stable disease (SD) and 8 (6.2%) progressive disease (PD). 25 pediatric high-grade gliomas showed CR; PR; SD; PD in 4 (16.0%); 10 (40.0%), 4 (16.0%); and 7 (28.0%) respectively. Thirty-nine adult low-grade gliomas showed CR; PR; SD; PD of 4 (10.3%); 17 (43.6%); 16 (41.0%) and 2 (5.1%) respectively. Ninety-seven adult high-grade gliomas showed CR; PR; SD; PD of 6 (6.2%); 31 (32.0%); 27 (27.8%); and 33 (34.0%) respectively.
CONCLUSIONS
BRAFV600 prevalence is highest in eGBM, PXA, aPXA, GG, aGG, and lower in astroblastoma, DIA, SEGA, DNET, DA, and PA. Our data provide the rationale for adjuvant clinical trials of BRAFi in V600-mutant glioma.
Topics: Adult; Astrocytoma; Brain Neoplasms; Child; Glioma; Humans; Mutation; Prevalence; Proto-Oncogene Proteins B-raf
PubMed: 34718782
DOI: 10.1093/neuonc/noab247 -
Asian Pacific Journal of Cancer... Oct 2021The aim of this study is to evaluate the association of c-Met overexpression with survival of glioblastoma multiforme (GBM) patients. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The aim of this study is to evaluate the association of c-Met overexpression with survival of glioblastoma multiforme (GBM) patients.
METHODS
A systematic review with meta-analyses was conducted on related articles from PubMed, EBSCOhost, Scopus, and Cochrane databases with last updated search on October 31, 2020. A total of 7 studies regarding c-Met overexpression and overall survival (OS) and/or progression free survival (PFS) are included in this study.
RESULTS
All studies used immunohistochemistry to examine the expression of c-Met protein. The results showed that the positive rate of c-Met overexpression was detected in approximately 33,9% - 60,5% of GBM patients. c-Met overexpression was related to worse OS (HR: 1,74; 95% CI: 1,482-2,043; Z=6,756; p<0,001) and PFS (HR: 1,66; 95% CI: 1,327-2,066; Z=4,464; p<0,001) in GBM patients. Low heterogeneity of subjects was found in both OS and PFS analyses, I2 values were 7,8% and 0,0%, respectively.
CONCLUSION
In conclusion, c-Met overexpression is significantly related to shorter OS and PFS in GBM patients, so c-Met can be considered as a potential prognostic indicator in GBM.
Topics: Brain Neoplasms; Glioblastoma; Humans; Kaplan-Meier Estimate; Prognosis; Progression-Free Survival; Proto-Oncogene Proteins c-met
PubMed: 34710981
DOI: 10.31557/APJCP.2021.22.10.3075 -
Critical Reviews in Oncology/hematology Nov 2021Despite a well-known prognostic role in colorectal cancer, the genomic profiling of tumour budding remains to be elucidated. We aim to review the association of common... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Despite a well-known prognostic role in colorectal cancer, the genomic profiling of tumour budding remains to be elucidated. We aim to review the association of common mutations with tumour budding.
METHODS
A systematic review of studies relating to tumour budding and genetic mutation in CRC was performed. The relationship between mutational status and tumour budding was evaluated using meta-analysis.
RESULTS
A total of 6153 patients from 17 articles were included. According to the meta-analysis, high-grade tumour budding was significantly associated with KRAS mutation (OR = 1.52, 95 %CI: 1.13-2.02, P = 0.005) and MSS/pMMR (OR = 2.06, 95 %CI: 1.42-2.97, P = 0.0001).
CONCLUSION
The significant association between high-grade tumour budding and mutated KRAS or MSS/pMMR may suggest a role of these mutations in the development of the tumour budding phenotype and be useful for stratifying patient outcome in CRC.
Topics: Colorectal Neoplasms; Humans; Mutation; Phenotype; Prognosis; Proto-Oncogene Proteins B-raf; Proto-Oncogene Proteins p21(ras)
PubMed: 34619332
DOI: 10.1016/j.critrevonc.2021.103490 -
Arab Journal of Urology 2021: To provide a summary of the current evaluation of azoospermia and insights into future perspectives in the evaluation and counselling of men with azoospermia. : A...
: To provide a summary of the current evaluation of azoospermia and insights into future perspectives in the evaluation and counselling of men with azoospermia. : A search of PubMed, Cochrane Reviews and Web of Science databases was performed for full-text English-language articles published between 1943 and 2020 focussing on 'future perspectives', 'azoospermia' and 'evaluation'. : Azoospermia represents a severe form of male infertility characterised by sperm production so impaired that there are no sperm present in the ejaculate. The current evaluation of azoospermia focusses on patient history and physical examination with selected adjunctive laboratory investigations including serum hormones, a karyotype and screening for Y chromosome microdeletions. Future diagnostics are focussed on identifying the underlying genetic aetiologies for azoospermia, as well as a greater emphasis on screening for systemic illness that men with severe infertility may be predisposed to develop. : Azoospermia represents an extreme form of male infertility, and evaluation relies heavily on history and physical examination, as genetic evaluations for these individuals remain limited. Future evaluation will focus on next-generation sequencing and more rigorous evaluation for possible co-existing and future risk of systemic disease. : ADGRG2, adhesion G protein-coupled receptor G2; ASRM: American Society of Reproductive Medicine; AZF: azoospermia factor; CBAVD: congenital bilateral absence of the vas deferens; CFTR: cystic fibrosis transmembrane conductance regulator; CRKL: CRK-like proto-oncogene; E2F1: E2F transcription factor 1; HAUS7: HAUS augmin-like complex subunit 7; HR: hazard ratio; KS: Klinefelter syndrome; MAZ, MYC-associated zinc finger protein; NGS: next-generation sequencing; NOA: non-obstructive azoospermia; OA: obstructive azoospermia; RHOX: reproductive homeobox on the X chromosome; SH2: SRC homology 2; TAF7L: TATA-box binding protein associated factor 7-like; TEX11: testis-expressed 11; WES: whole-exome sequencing.
PubMed: 34552771
DOI: 10.1080/2090598X.2021.1954415