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Mutation Research. Reviews in Mutation... 2023The development of resistance by tumor cells to various types of therapy is a significant problem that decreases the effectiveness of oncology treatments. For more than... (Review)
Review
The development of resistance by tumor cells to various types of therapy is a significant problem that decreases the effectiveness of oncology treatments. For more than two decades, comparative transcriptomic studies of tumor cells with different sensitivities to ionizing radiation and chemotherapeutic agents have been conducted in order to identify the causes and mechanisms underlying this phenomenon. However, the results of such studies have little in common and often contradict each other. We have assumed that a systematic analysis of a large number of such studies will provide new knowledge about the mechanisms of development of therapeutic resistance in tumor cells. Our comparison of 123 differentially expressed gene (DEG) lists published in 98 papers suggests a very low degree of consistency between the study results. Grouping the data by type of genotoxic agent and tumor type did not increase the similarity. The most frequently overexpressed genes were found to be those encoding the transport protein ABCB1 and the antiviral defense protein IFITM1. We put forward a hypothesis that the role played by the overexpression of the latter in the development of resistance may be associated not only with the stimulation of proliferation, but also with the limitation of exosomal communication and, as a result, with a decrease in the bystander effect. Among down regulated DEGs, BNIP3 was observed most frequently. The expression of BNIP3, together with BNIP3L, is often suppressed in cells resistant to non-platinum genotoxic chemotherapeutic agents, whereas it is increased in cells resistant to ionizing radiation. These observations are likely to be mediated by the binary effects of these gene products on survival, and regulation of apoptosis and autophagy. The combined data also show that even such obvious mechanisms as inhibition of apoptosis and increase of proliferation are not universal but show multidirectional changes.
Topics: Humans; Gene Expression Profiling; Transcriptome; RNA; Apoptosis; DNA Damage
PubMed: 37657754
DOI: 10.1016/j.mrrev.2023.108467 -
BMC Cancer Feb 2021Breast cancer (BC) is a leading cause of cancer-related death in females worldwide. Previous studies have demonstrated that matrix metalloproteinases (MMPs) play key... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Breast cancer (BC) is a leading cause of cancer-related death in females worldwide. Previous studies have demonstrated that matrix metalloproteinases (MMPs) play key roles in metastasis and are associated with survival in various cancers. The prognostic values of MMP2 and MMP9 expression in BC have been investigated, but the results remain controversial. Thus, we performed the present meta-analysis to investigate the associations between MMP2/9 expressions in tumor cells with clinicopathologic features and survival outcome in BC patients.
METHODS
Eligible studies were searched in PubMed, Web of Science, EMBASE, CNKI and Wanfang databases. The associations of MMP2/9 overexpression in tumor cells with overall survival (OS), disease-free survival (DFS) and recurrence-free survival (RFS) were assessed by hazard ratio (HR) and 95% confidence interval (CI). The associations of MMP2/9 overexpression with clinicopathological features were investigated by calculating odds ratio (OR) and 95% CI. Subgroup analysis, sensitivity analysis, meta-regression, and analysis for publication bias were performed.
RESULTS
A total of 41 studies comprising 6517 patients with primary BC were finally included. MMP2 overexpression was associated with an unfavorable OS (HR = 1.60, 95% CI 1.33 -1.94, P < 0.001) while MMP9 overexpression predicted a shorter OS (HR = 1.52, 95% CI 1.30 -1.77, P < 0.001). MMP2 overexpression conferred a higher risk to distant metastasis (OR = 2.69, 95% CI 1.35-5.39, P = 0.005) and MMP9 overexpression correlated with lymph node metastasis (OR = 2.90, 95% CI 1.86 - 4.53, P < 0.001). Moreover, MMP2 and MMP9 overexpression were both associated with higher clinical stage and histological grade in BC patients. MMP9 overexpression was more frequent in patients with larger tumor sizes.
CONCLUSIONS
Tumoral MMP2 and MMP9 are promising markers for predicting the prognosis in patients with BC.
Topics: Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Prognosis; Survival Rate
PubMed: 33568081
DOI: 10.1186/s12885-021-07860-2 -
Genetic Testing and Molecular Biomarkers Jun 2022Dysregulation of the SET and MYND domain-containing protein 3 () has been found in multiple cancers. This meta-analysis aimed to elucidate the association between... (Meta-Analysis)
Meta-Analysis
Dysregulation of the SET and MYND domain-containing protein 3 () has been found in multiple cancers. This meta-analysis aimed to elucidate the association between expression and clinical outcomes in cancer. A systematic search of Web of Science, Embase, PubMed, Cochrane Library, and CNKI was conducted. The relationship between expression and cancer patients' overall survival (OS) was evaluated using pooled hazard ratios (HRs) and their corresponding confidence intervals (95% CIs). The association between expression and clinicopathological features was assessed using odds ratios (ORs) with 95% CIs, including tumor size, lymph node metastasis (LNM), distance metastasis, and TNM stage. In total, 715 cancer patients with hepatocellular carcinoma, nonsmall cell lung carcinoma, esophageal squamous cell carcinoma, glioma, colorectal cancer, and/or bladder cancer from seven studies were included in our meta-analysis. overexpression was significantly associated with poor OS (HR = 1.81, 95% CI: 1.38-2.37, < 0.01) with no heterogeneity ( = 0.0%, = 0.929) in various cancers. Subgroup analysis showed that the prognostic value of across multiple tumors was constant as the tumor type, sample size, and methods of data extraction changed. Increased expression was positively associated with LNM (OR = 1.88, 95% CI = 1.33-2.66, < 0.001), tumor size (OR = 1.68, 95% CI: 1.09-2.60, = 0.019), and advanced TNM stage (OR = 1.84, 95% CI: 1.25-2.69, = 0.002). Upregulation of was significantly associated with poor prognosis in various cancers, suggesting that may be a useful prognostic biomarker.
Topics: Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Histone-Lysine N-Methyltransferase; Humans; Lymphatic Metastasis; Prognosis
PubMed: 35763383
DOI: 10.1089/gtmb.2021.0199 -
Oral Oncology Jun 2021Epithelial-mesenchymal transition (EMT) is considered the initial step in the invasion-metastasis cascade. The aim of this systematic review was to study the signature... (Review)
Review
OBJECTIVE
Epithelial-mesenchymal transition (EMT) is considered the initial step in the invasion-metastasis cascade. The aim of this systematic review was to study the signature of genes involved in the EMT process in oral cancer (OC) confirmed by protein expression and its possible relationship with oral squamous cell carcinoma (OSCC) prognostic variables.
MATERIALS AND METHODS
A search of the scientific literature was carried out with no start date restriction until 17 September 2020 in the electronic databases Pubmed/MEDLINE, Web of Science, Cochrane Library and Scopus, following specific eligibility criteria. The methodological quality of the included studies was assessed using the Newcastle-Ottawa tool.
RESULTS
A total of 8 retrospective cohort studies were included, all of them performed in China and with low risk of bias. Overexpression of the genes HNRNPC, ITGA5, HMGA2 and SRSF3, and low expression of ALDH3A1 and ARID2 promote EMT in OC. The more advanced clinical stages of the TNM classification were significantly associated with overexpression of HNRNPC, ITGA5, HMGA2 and SRSF3, and low expression of ARID2.
CONCLUSIONS
HNRNPC, ITGA5, HMGA2, SRSF3, ALDH3A1 and ARID2 genes were associated with EMT process. Over- or under-expression of these genes is associated with worse stages of OSCC and/or worse prognosis of the tumor. Further studies on this topic are needed in different countries to be able to confirm these results, since the detection of these genes can help to know which tumors have a worse prognosis.
Topics: Epithelial-Mesenchymal Transition; Humans; Mouth Neoplasms; Retrospective Studies; Squamous Cell Carcinoma of Head and Neck; Transcription Factors
PubMed: 33901766
DOI: 10.1016/j.oraloncology.2021.105310 -
Leukemia Research Oct 2022Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk molecular subtype with a gene expression profile similar to Philadelphia-positive ALL, but... (Review)
Review
Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL) is a high-risk molecular subtype with a gene expression profile similar to Philadelphia-positive ALL, but not harboring the BCR-ABL1 gene fusion. We aimed to investigate the efficacy of target therapy with the Janus kinase inhibitor, ruxolitinib, in patients with Ph-like ALL and molecular signature of JAK-STAT signaling pathway. A systematic search of the literature was performed to identify reports concerning administration of ruxolitinib in Ph-like ALL patients. Additionally, Polish Pediatric ALL registries were searched for patients with Ph-like ALL treated with ruxolitinib. Extracted information included epidemiological background, somatic aberrations, treatment response, and patient outcome. After PubMed database search, twelve patients were identified, and one was identified in the Polish Pediatric ALL registry. In nine patients gene fusions affecting JAK2 (n = 7) and EPOR (n = 2) were detected. Surface overexpression of CRLF2 and IKZF1 deletions were observed in two and three patients, respectively. Induction failure occurred in all the patients. Therapy with ruxolitinib led to complete (n = 7) and partial (n = 2) remission, in three individuals no information was found. Based on the limited number of studies describing the efficacy of ruxolitinib as an additional compound administrated with standard ALL therapy, we conclude that this approach can be considered in patients with aberrations activating JAK-STAT pathway.
Topics: Child; Humans; Janus Kinase Inhibitors; Janus Kinases; Nitriles; Philadelphia Chromosome; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pyrazoles; Pyrimidines; STAT Transcription Factors; Signal Transduction
PubMed: 35939887
DOI: 10.1016/j.leukres.2022.106925 -
Cancers Jul 2022The aim of this systematic review and meta-analysis was to evaluate the current evidence on the prognostic and clinicopathological significance value of telomerase... (Review)
Review
The aim of this systematic review and meta-analysis was to evaluate the current evidence on the prognostic and clinicopathological significance value of telomerase reverse transcriptase (TERT) upregulation in patients with oral squamous cell carcinoma (OSCC). PubMed, Embase, Web of Science, and Scopus were searched for studies published before April 2022, not restricted by date or publication language. The methodological quality of primary-level studies was critically assessed using the Quality in Prognosis Studies (QUIPS) tool. We carried out meta-analyses, explored heterogeneity and its sources, and performed subgroup, meta-regression, sensitivity, and small-study effects analyses. Twenty-one studies (1698 patients) met inclusion criteria. TERT protein overexpression was significantly associated with worse overall survival (hazard ratio [HR] = 3.01, 95% CI = 1.70−5.35, p < 0.001), disease-free survival (HR = 4.03, 95% CI = 1.80−9.05, p = 0.001), and higher histological grade OSCC (odds ratio [OR] = 3.20, 95% CI = 1.83−5.62, p < 0.001). These large effect sizes were consistently obtained by homogeneous subgroups (p > 0.10, I2 = 0.0, respectively), which reflects a high quality of evidence. On the other hand, TERT gene mutations obtained constantly nonsignificant null effect sizes for all outcomes investigated, evidencing no prognostic or clinicopathological value. In conclusion, our findings indicate that TERT upregulation is a prognostic indicator of poor survival in oral cancer. Our findings support the immunohistochemical assessment of TERT overexpression, which could probably be incorporated into the prognostic evaluation of OSCC.
PubMed: 35954336
DOI: 10.3390/cancers14153673 -
Cancers Aug 2020Fas-associated death domain (FADD) upregulation, i.e., gene amplification, protein phosphorylation and/or overexpression, has shown promising prognostic implications in... (Review)
Review
Fas-associated death domain (FADD) upregulation, i.e., gene amplification, protein phosphorylation and/or overexpression, has shown promising prognostic implications in head and neck squamous cell carcinoma (HNSCC). This systematic review and meta-analysis aims to evaluate the clinicopathological and prognostic significance of FADD upregulation in HNSCC. We searched studies published before February 2020 through PubMed, Embase, Web of Science, Scopus and Google Scholar. We evaluated the quality of the studies included using the QUIPS tool. The impact of FADD upregulation on survival and clinicopathological variables was meta-analysed. We explored heterogeneity and their sources, conducted sensitivity analyses and investigated small-study effects. Thirteen studies (1,923 patients) met inclusion criteria. FADD immunohistochemical overexpression was statistically associated with worse overall survival (hazard ratio [HR] = 1.52, 95% confidence intervals [CI] = 1.28-1.81, < 0.001), disease-specific survival (HR = 2.52, 95% CI = 1.61-3.96, < 0.001), disease-free survival (HR = 1.67, 95% CI=1.29-2.15, < 0.001), higher clinical stage (odds ratio [OR] = 1.72, 95% CI = 1.17-2.51, = 0.005) and a large magnitude of effect with N+ status (OR = 2.36, 95% CI = 1.85-3.00, < 0.001). FADD phosphorylation in ser-194 demonstrated no prognostic value, while no conclusive results can be drawn for FADD gene amplification. In conclusion, our findings indicate that immunohistochemical assessment of FADD overexpression could be incorporated into the prognostic evaluation of HNSCC.
PubMed: 32847023
DOI: 10.3390/cancers12092393 -
Cancer Epidemiology Dec 2021Clinical breast cancer subtypes are categorized basing on the expression of hormone receptors and overexpression of the human epidermal growth factor receptor 2 (HER2).... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Clinical breast cancer subtypes are categorized basing on the expression of hormone receptors and overexpression of the human epidermal growth factor receptor 2 (HER2). It is still unclear whether parity impact the risk of different breast cancer subtypes.
METHODS
We searched eight mainstream databases for published epidemiologic studies that assessed the relationship between parity and risk of breast cancer subtypes up to January 12, 2021. Parity number were unified into nulliparity and ever parity. The random-effects or fixed-effect models were used to calculate the pooled odds ratios (ORs) and 95% confidence intervals (CIs) among different subtypes. Restricted cubic spline analysis with four knots was applied to determine the relationship of parity number and risk of breast cancer subtypes.
RESULTS
We pooled sixteen case-control and four cohort studies, and performed an analysis including 7795 luminal A, 3576 luminal B, 1794 HER2-overexpressing, and 5192 triple-negative breast cancer cases among 1135131 participants. The combined ORs for ever parity versus nulliparity indicated a 34% reduction in luminal A risk (OR=0.66, 95% CI: 0.56-0.78), and a 29% reduction in luminal B risk (OR=0.71, 95% CI: 0.63-0.81), there was no significant association in HER2-overexpressing or TNBC risk. In the dose-response analysis, we observed a potentially non-linear and gradually increasing protective relationship between the number of parity and luminal breast cancer risk.
CONCLUSIONS
The effect of parity on breast cancer seems to vary among breast tumor subtypes, and it plays a protective role in luminal breast cancer.
Topics: Biomarkers, Tumor; Breast Neoplasms; Female; Humans; Parity; Pregnancy; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Risk Factors; Triple Negative Breast Neoplasms
PubMed: 34706325
DOI: 10.1016/j.canep.2021.102050 -
Iranian Journal of Allergy, Asthma, and... Apr 2020Despite the importance of CD44 and CD133 in various cancers, the clinicopathological and prognostic values of these biomarkers in esophageal cancer remain debated.... (Meta-Analysis)
Meta-Analysis
Despite the importance of CD44 and CD133 in various cancers, the clinicopathological and prognostic values of these biomarkers in esophageal cancer remain debated. Hence, in this study, we did a meta-analysis to explore the correlation between overexpression of these markers and some clinicopathological features and their influence on the survival of esophageal cancer patients. A search in PubMed and Web of Science (among all articles published up to January 16, 2018) was done using the following keywords: esophageal cancer, CD44, CD133, prominin-1, AC133. Suitable studies, that were selected based on the criteria listed in the Materials and Methods section, were chosen and hazard ratios with 95% confidence intervals were estimated if available. Heterogeneity and sensitivity were also analyzed. Furthermore, publication bias was assessed using funnel plots, Egger, and Begg tests. The study included 1346 patients from 13 related studies. The median rates of marker expressions by immunohistochemistry were 35.7% (30%-76.6%) from 9 studies for CD44 and 31.9% (21%-44.2%) from 5 studies for CD133. The accumulative 5-year overall survival rates of CD44-positive and CD133-positive were 1.59% (1.22-2.06) and 1.27% (0.93-1.73), respectively. Meta-analysis showed that CD44 expression had a significant correlation with 5-year overall survival. CD44 overexpression showed a correlation with some clinicopathological features such as lymph node metastasis, vascular invasion, and recurrence of the disease, while it was not the case for coexpression of CD44 and CD133. In conclusion, CD44 overexpression was associated with a 5-year overall survival rate and thus this biomarker can be a suitable prognostic tool in esophageal cancer.
Topics: Biomarkers, Tumor; CD13 Antigens; Esophageal Neoplasms; Esophagus; Gene Expression Regulation, Neoplastic; Humans; Hyaluronan Receptors; Immunohistochemistry; Lymphatic Metastasis; Neoplasm Recurrence, Local; Predictive Value of Tests; Prognosis; Survival Analysis
PubMed: 32372624
DOI: 10.18502/ijaai.v19i2.2756 -
PloS One 2021The reported rates of HER2 positivity in cervical cancer (CC) range from 0% to 87%. The importance of HER2 as an actionable target in CC would depend on HER2 positivity... (Meta-Analysis)
Meta-Analysis
The reported rates of HER2 positivity in cervical cancer (CC) range from 0% to 87%. The importance of HER2 as an actionable target in CC would depend on HER2 positivity prevalence. Our aim was to provide precise estimates of HER2 overexpression and amplification in CC, globally and by relevant subgroups. We conducted a PRISMA compliant meta-analytic systematic review. We searched Medline, EMBASE, Cochrane database, and grey literature for articles reporting the proportion of HER2 positivity in CC. Studies assessing HER2 status by immunohistochemistry or in situ hybridization in invasive disease were eligible. We performed descriptive analyses of all 65 included studies. Out of these, we selected 26 studies that used standardized American Society of Clinical Oncology / College of American Pathologists (ASCO/CAP) Guidelines compliant methodology. We conducted several meta-analyses of proportions to estimate the pooled prevalence of HER2 positivity and subgroup analyses using geographic region, histology, tumor stage, primary antibody brand, study size, and publication year as moderators. The estimated pooled prevalence of HER2 overexpression was 5.7% (CI 95%: 1.5% to 11.7%) I2 = 87% in ASCO/CAP compliant studies and 27.0%, (CI 95%: 19.9% to 34.8%) I2 = 96% in ASCO/CAP non-compliant ones, p < 0.001. The estimated pooled prevalence of HER2 amplification was 1.2% (CI 95%: 0.0% to 5.8%) I2 = 0% and 24.9% (CI 95%: 12.6% to 39.6%) I2 = 86%, respectively, p = 0.004. No other factor was significantly associated with HER2 positivity rates. Our results suggest that a small, but still meaningful proportion of CC is expected to be HER2-positive. High heterogeneity was the main limitation of the study. Variations in previously reported HER2 positivity rates are mainly related to methodological issues.
Topics: Female; Gene Amplification; Gene Expression Regulation, Neoplastic; Humans; Receptor, ErbB-2; Uterine Cervical Neoplasms
PubMed: 34591928
DOI: 10.1371/journal.pone.0257976