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Cancers Jul 2022Neuropilin-1 (NRP1) is a transmembrane protein involved in numerous cellular functions which has had increasing interest from cancer researchers. Liver cancer and... (Review)
Review
Neuropilin-1 (NRP1) is a transmembrane protein involved in numerous cellular functions which has had increasing interest from cancer researchers. Liver cancer and colorectal cancer (CRC) are two of the most frequent and deadly tumors with a complex pharmacological framework. Here, we assessed the prognostic, diagnostic and clinicopathological value of NRP1 in liver cancer and CRC patients. We searched PubMed, Scopus, Web of Science, Embase and Cochrane Library databases for articles evaluating the NRP1 correlation with survival parameters, tumor development or clinicopathological features. Hazard ratios and odds ratios with 95% confidence intervals were extracted or estimated by Parmar method and pooled to evaluate the overall effect size with STATA 16 software. Heterogeneity was analyzed by chi-square-based Q test and I statistic, along with meta-regression and subgroup analysis, and publication bias was assessed by funnel plot asymmetry and Egger's test. The study protocol was registered in PROSPERO (CRD42022307062). NRP1 overexpression was significantly correlated with lower survival in liver cancer patients and with tumor development in hepatocarcinoma patients, and was strongly correlated with an increased risk of vascular invasion in liver cancer and metastasis in CRC and liver tumors. These results support the role of NRP1 as a potential and useful biomarker in both types of cancer.
PubMed: 35884516
DOI: 10.3390/cancers14143455 -
Cancers Jul 2020Aquaporin (AQP) channels enable regulated transport of water and solutes essential for fluid homeostasis, but they are gaining attention as targets for anticancer...
Aquaporin (AQP) channels enable regulated transport of water and solutes essential for fluid homeostasis, but they are gaining attention as targets for anticancer therapies. Patterns of AQP expression and survival rates for patients were evaluated by systematic review (PubMed and Embase) and transcriptomic analyses of RNAseq data (Human Protein Atlas database). Meta-analyses confirmed predominantly negative associations between AQP protein and RNA expression levels and patient survival times, most notably for AQP1 in lung, breast and prostate cancers; AQP3 in esophageal, liver and breast cancers; and AQP9 in liver cancer. Patterns of AQP expression were clustered for groups of cancers and associated with risk of death. A quantitative transcriptomic analysis of AQP1-10 in human cancer biopsies similarly showed that increased transcript levels of AQPs 1, 3, 5 and 9 were most frequently associated with poor survival. Unexpectedly, increased AQP7 and AQP8 levels were associated with better survival times in glioma, ovarian and endometrial cancers, and increased AQP11 with better survival in colorectal and breast cancers. Although molecular mechanisms of aquaporins in pathology or protection remain to be fully defined, results here support the hypothesis that overexpression of selected classes of AQPs differentially augments cancer progression. Beyond fluid homeostasis, potential roles for AQPs in cancers (suggested from an expanding appreciation of their functions in normal tissues) include cell motility, membrane process extension, transport of signaling molecules, control of proliferation and apoptosis, increased mechanical compliance, and gas exchange. AQP expression also has been linked to differences in sensitivity to chemotherapy treatments, suggesting possible roles as biomarkers for personalized treatments. Development of AQP pharmacological modulators, administered in cancer-specific combinations, might inspire new interventions for controlling malignant carcinomas.
PubMed: 32679804
DOI: 10.3390/cancers12071911 -
Frontiers in Oncology 2020Current reports on the prognostic and predictive value of hypoxia-inducible factor-1α (HIF-1α) in endometrial carcinoma are inconsistent. Therefore, we conducted this...
BACKGROUND
Current reports on the prognostic and predictive value of hypoxia-inducible factor-1α (HIF-1α) in endometrial carcinoma are inconsistent. Therefore, we conducted this meta-analysis to precisely evaluate the association of HIF-1α expression with susceptibility, clinical features, and prognosis of endometrial cancer.
METHODS
Eligible studies that assessed the role of HIF-1α protein expression, immunohistochemistry detection, disease susceptibility, clinical features, and prognosis of endometrial cancer were searched from the Embase, Pubmed, and Web of Science databases. Stata 14.0 software was used to merge and compute pooled hazard ratios (HR) and odds ratios (OR). Information including HIF-1α protein expression and clinical progression of endometrial cancer was extracted. The pooled HR and OR with corresponding 95% confidence intervals (CI) were used to estimate the strength of these associations.
RESULTS
A total of 25 studies were included in the analysis. HIF-1α protein expression in endometrial cancer tissue was significantly higher than that in normal tissues (OR = 15.79, 95% CI = 8.44-29.52, < 0.05). Endometrial cancer patients with higher HIF-1α protein expression had poorer prognosis compared to patients with low HIF-1α protein expression (HR = 2.29, 95% CI = 1.68-2.90, < 0.05). In addition, high HIF-1α protein expression was significantly associated with endometrial cancer grade, lymph node metastasis, and myometrial invasion (grade in Caucasians: OR = 3.09, 95% CI = 1.63-5.85, < 0.05; lymph node metastasis: OR = 3.09, 95% CI = 1.63-5.85, < 0.05; myometrial invasion: OR = 2.26, 95% CI = 2.15-5.08, < 0.05).
CONCLUSIONS
HIF-1α overexpression was significantly associated with increased risk, advanced clinical progression, and poor prognosis in endometrial cancer patients.
PubMed: 33304847
DOI: 10.3389/fonc.2020.587420 -
Medicine Jan 2021Heat-shock proteins (HSP) is a key chaperone protein which maintains intracellular proteostasis and is expressed on the surface of solid and hematological malignancies.... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Heat-shock proteins (HSP) is a key chaperone protein which maintains intracellular proteostasis and is expressed on the surface of solid and hematological malignancies. Several studies have reported paradoxical evidence of the association between HSP expression and prognosis of oral cancer. To address the discrepancy, we carried out the meta-analysis to assess the role of HSP such as: HSP70, HSP90, HSP27, HSP60, and HSP105 in susceptibility, progression, and prognosis of oral cancer.
MATERIALS AND METHODS
We retrieved the PubMed, Embase, Web of science, China National Knowledge Infrastructure (CNKI), and Wanfang databases to acquire the eligible studies which were associated with HSP70, HSP90, HSP27, HSP60, and HSP105 protein expression and oral cancer. We applied hazard ratio (HR) and its 95% confidence interval (95% CI) to assess the value of HSP protein expression in overall survival of oral cancer; odds ratio (OR) and its 95% CI were used to evaluate the association of risk and clinical features of oral cancer. Funnel plot, Begg test, and Egger line regression test were utilized to observe publication bias among studies. All statistical analysis was performed with Stata 14.0 software (Stata Corporation, College Station, TX).
RESULTS
A total of 26 studies were included in the present meta-analysis. On based of the results, HSP70 and HSP27 had no significant association with progression of oral cancer. However, the pooled HR and 95% CI revealed a significant well effects of HSP70 and HSP27 expression on survival of oral cancer. Moreover, the susceptibility of oral cancer was significantly associated with HSP70 and HSP60 overexpression.
CONCLUSION
HSP70 and HSP27 protein overexpression might be valuable biomarkers for the prognosis of oral cancer. And HSP70 and HSP60 might have potential predictive effects on the risk of oral cancer.
Topics: HSP70 Heat-Shock Proteins; Heat-Shock Proteins; Humans; Mouth Neoplasms; Prognosis; Proportional Hazards Models
PubMed: 33546049
DOI: 10.1097/MD.0000000000024274 -
PloS One 2024Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results.... (Meta-Analysis)
Meta-Analysis
Meningioma is the most common primary brain tumor and many studies have evaluated numerous biomarkers for their prognostic value, often with inconsistent results. Currently, no reliable biomarkers are available to predict the survival, recurrence, and progression of meningioma patients in clinical practice. This study aims to evaluate the prognostic value of immunohistochemistry-based (IHC) biomarkers of meningioma patients. A systematic literature search was conducted up to November 2023 on PubMed, CENTRAL, CINAHL Plus, and Scopus databases. Two authors independently reviewed the identified relevant studies, extracted data, and assessed the risk of bias of the studies included. Meta-analyses were performed with the hazard ratio (HR) and 95% confidence interval (CI) of overall survival (OS), recurrence-free survival (RFS), and progression-free survival (PFS). The risk of bias in the included studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool. A total of 100 studies with 16,745 patients were included in this review. As the promising markers to predict OS of meningioma patients, Ki-67/MIB-1 (HR = 1.03, 95%CI 1.02 to 1.05) was identified to associate with poor prognosis of the patients. Overexpression of cyclin A (HR = 4.91, 95%CI 1.38 to 17.44), topoisomerase II α (TOP2A) (HR = 4.90, 95%CI 2.96 to 8.12), p53 (HR = 2.40, 95%CI 1.73 to 3.34), vascular endothelial growth factor (VEGF) (HR = 1.61, 95%CI 1.36 to 1.90), and Ki-67 (HR = 1.33, 95%CI 1.21 to 1.46), were identified also as unfavorable prognostic biomarkers for poor RFS of meningioma patients. Conversely, positive progesterone receptor (PR) and p21 staining were associated with longer RFS and are considered biomarkers of favorable prognosis of meningioma patients (HR = 0.60, 95% CI 0.41 to 0.88 and HR = 1.89, 95%CI 1.11 to 3.20). Additionally, high expression of Ki-67 was identified as a prognosis biomarker for poor PFS of meningioma patients (HR = 1.02, 95%CI 1.00 to 1.04). Although only in single studies, KPNA2, CDK6, Cox-2, MCM7 and PCNA are proposed as additional markers with high expression that are related with poor prognosis of meningioma patients. In conclusion, the results of the meta-analysis demonstrated that PR, cyclin A, TOP2A, p21, p53, VEGF and Ki-67 are either positively or negatively associated with survival of meningioma patients and might be useful biomarkers to assess the prognosis.
Topics: Meningioma; Humans; Biomarkers, Tumor; Prognosis; Meningeal Neoplasms; DNA Topoisomerases, Type II; Ki-67 Antigen; Tumor Suppressor Protein p53; Vascular Endothelial Growth Factor A; Immunohistochemistry; Poly-ADP-Ribose Binding Proteins
PubMed: 38758750
DOI: 10.1371/journal.pone.0303337 -
International Journal of Molecular... Oct 2022The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for... (Review)
Review
The characteristic epigenetic profile of periodontitis found in peripheral leukocytes denotes its impact on systemic immunity. In fact, this profile not only stands for periodontitis as a low-grade inflammatory disease with systemic effects but also as an important source of potentially valuable clinical biomarkers of its systemic effects and susceptibility to other inflammatory conditions. Thus, we aimed to identify relevant genes tested as epigenetic systemic biomarkers in patients with periodontitis, based on the DNA methylation patterns and RNA expression profiles in peripheral immune cells. A detailed protocol was designed following the Preferred Reporting Items for Systematic Review and Meta-analysis -PRISMA guideline. Only cross-sectional and case-control studies that reported potential systemic biomarkers of periodontitis in peripheral immune cell types were included. DNA methylation was analyzed in leukocytes, and gene expression was in polymorphonuclear and mononuclear cells. Hypermethylation was found in TLR regulators genes: , , , , , , and in early stages of periodontitis, while advanced stages presented hypomethylation of these genes. , , , and genes were differentially expressed in lymphocytes and monocytes of subjects with poorly controlled diabetes mellitus, dyslipidemia, and periodontitis in comparison with controls. The gene was differentially overexpressed in periodontitis and dyslipidemia. Peripheral blood neutrophils in periodontitis showed differential expression in 163 genes. Periodontitis showed an increase in ceruloplasmin gene expression in polymorphonuclears in comparison with controls. Several genes highlight the role of the epigenetics of peripheral inflammatory cells in periodontitis that could be explored in blood as a source of biomarkers for routine testing.
Topics: Biomarkers; Ceruloplasmin; Cross-Sectional Studies; DNA Methylation; Dyslipidemias; Gene Expression; Humans; Myeloid Differentiation Factor 88; Periodontitis; RNA
PubMed: 36233348
DOI: 10.3390/ijms231912042 -
Cancers Nov 2021Poly (ADP-ribose) polymerase (PARP) is a DNA damage repair protein, and its inhibitors have shown promising results in clinical trials. The prognostic significance of... (Review)
Review
Poly (ADP-ribose) polymerase (PARP) is a DNA damage repair protein, and its inhibitors have shown promising results in clinical trials. The prognostic significance of PARP is inconsistent in studies of various cancers. In the present study, we conducted a systematic review and meta-analysis to reveal the prognostic and clinicopathological significance of PARP expression in multiple solid cancers. We searched the MEDLINE, EMBASE, and Cochrane databases for relevant research articles published from 2005 to 2021. The pooled hazard ratio (HR) with confidence interval (CI) was calculated to investigate the relationship between PARP expression and survival in multiple solid cancers. In total, 10,667 patients from 31 studies were included. A significant association was found between higher PARP expression and overall survival (OS) (HR = 1.54, 95% CI = 1.34-1.76, < 0.001), disease-free survival (DFS) (HR = 1.15, 95% CI = 1.10-1.21, < 0.001), and progression-free survival (PFS) (HR = 1.05, 95% CI = 1.03-1.08, < 0.001). Subgroup analyses showed that PARP overexpression was significantly related to poor OS in patients with breast cancers (HR = 1.38, 95% CI = 1.28-1.49, < 0.001), ovary cancers (HR = 1.21, 95% CI = 1.10-1.33, = 0.001), lung cancers (HR = 2.11, 95% CI = 1.29-3.45, = 0.003), and liver cancers (HR = 3.29, 95% CI = 1.94-5.58, < 0.001). Regarding ethnicity, Asian people have almost twice their worst survival rate compared to Caucasians. The pooled odds ratio analysis showed a significant relationship between higher PARP expression and larger tumour size, poor tumour differentiation, lymph node metastasis, distant metastasis, higher TNM stage and lymphovascular invasion, and positive immunoreactivity for Ki-67, BRCA1, and BRCA2. In addition, nuclear expression assessed by the QS system using Abcam and Santa Cruz Biotechnology seems to be the most commonly used and reproducible IHC method for assessing PARP expression. This meta-analysis revealed that higher PARP expression was associated with a worse OS, DFS, and PFS in patients with solid cancers. Moreover, inhibition of this pathway through its specific inhibitors may extend the survival of patients with higher PARP expression.
PubMed: 34830749
DOI: 10.3390/cancers13225594 -
Biology of Sex Differences Jan 2024The incidence of Alzheimer's disease (AD)-the most frequent cause of dementia-is expected to increase as life expectancies rise across the globe. While sex-based... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The incidence of Alzheimer's disease (AD)-the most frequent cause of dementia-is expected to increase as life expectancies rise across the globe. While sex-based differences in AD have previously been described, there remain uncertainties regarding any association between sex and disease-associated molecular mechanisms. Studying sex-specific expression profiles of regulatory factors such as microRNAs (miRNAs) could contribute to more accurate disease diagnosis and treatment.
METHODS
A systematic review identified six studies of microRNA expression in AD patients that incorporated information regarding the biological sex of samples in the Gene Expression Omnibus repository. A differential microRNA expression analysis was performed, considering disease status and patient sex. Subsequently, results were integrated within a meta-analysis methodology, with a functional enrichment of meta-analysis results establishing an association between altered miRNA expression and relevant Gene Ontology terms.
RESULTS
Meta-analyses of miRNA expression profiles in blood samples revealed the alteration of sixteen miRNAs in female and 22 miRNAs in male AD patients. We discovered nine miRNAs commonly overexpressed in both sexes, suggesting a shared miRNA dysregulation profile. Functional enrichment results based on miRNA profiles revealed sex-based differences in biological processes; most affected processes related to ubiquitination, regulation of different kinase activities, and apoptotic processes in males, but RNA splicing and translation in females. Meta-analyses of miRNA expression profiles in brain samples revealed the alteration of six miRNAs in female and four miRNAs in male AD patients. We observed a single underexpressed miRNA in female and male AD patients (hsa-miR-767-5p); however, the functional enrichment analysis for brain samples did not reveal any specifically affected biological process.
CONCLUSIONS
Sex-specific meta-analyses supported the detection of differentially expressed miRNAs in female and male AD patients, highlighting the relevance of sex-based information in biomedical data. Further studies on miRNA regulation in AD patients should meet the criteria for comparability and standardization of information.
Topics: Humans; Male; Female; Alzheimer Disease; MicroRNAs; Brain
PubMed: 38297404
DOI: 10.1186/s13293-024-00588-1 -
BMC Cancer Sep 2020An increasing number of studies have described the aberrant expression of homeobox (HOX) proteins in gastric cancer (GC), which is critically associated with the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
An increasing number of studies have described the aberrant expression of homeobox (HOX) proteins in gastric cancer (GC), which is critically associated with the prognosis and clinicopathological characteristics of GC. This study was conducted to investigate the clinical value and action mechanisms of HOX proteins in GC.
METHODS
A comprehensive search of PubMed, Embase, Web of Science and Cochrane Library was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. The pooled hazard ratio (HR) with its 95% confidence interval (95% CI) and the pooled odds ratio (OR) with its 95% CI were used to assess the effect of HOX protein expression on the prognosis and clinicopathological features of GC, respectively.
RESULTS
Nineteen studies containing 3775 patients were selected for this study. Heterogeneity among HRs of overall survival (OS) was markedly high (I = 90.5%, p = 0.000). According to the subgroup analysis, increased expression of HOX protein in the downregulated subgroup was associated with a good prognosis for patients with GC (pooled HR: 0.46, 95% CI: 0.36-0.59, I = 3.1%, p = 0.377), while overexpression of HOX protein in the upregulated subgroup was correlated with a reduced OS (pooled HR: 2.59, 95% CI: 1.79-3.74, I = 73.5%, p = 0.000). The aberrant expression of HOX protein was crucially related to the TNM stage, depth of tumour invasion, tumour size, lymph node metastasis, distant metastasis, vascular invasion, histological differentiation and Lauren classification in patients with GC. In addition, the molecular mechanisms by which HOX proteins regulate tumorigenesis and development of GC were also explored.
CONCLUSIONS
HOX proteins play vital roles in GC progression, which might serve as prognostic markers and therapeutic targets for GC.
Topics: Biomarkers, Tumor; Disease Progression; Homeodomain Proteins; Humans; Lymphatic Metastasis; Molecular Targeted Therapy; Prognosis; Proportional Hazards Models; Stomach Neoplasms
PubMed: 32907552
DOI: 10.1186/s12885-020-07346-7 -
Frontiers in Oncology 2022Dysregulation of the mesenchymal epithelial transition (MET) pathway contributes to poor clinical outcomes in patients with non-small cell lung cancer (NSCLC). Numerous... (Review)
Review
BACKGROUND
Dysregulation of the mesenchymal epithelial transition (MET) pathway contributes to poor clinical outcomes in patients with non-small cell lung cancer (NSCLC). Numerous clinical trials are currently investigating several therapies based on modulation of the MET pathway.
OBJECTIVES
This study aimed to systematically evaluate the activity and safety of MET inhibitors in patients with NSCLC.
METHODS
We searched PubMed, Embase, and the Cochrane Library from inception to June 02, 2022. The objective response rate (ORR) and disease control rate (DCR) were extracted as the main outcomes and pooled using the weighted mean proportion with fixed- or random-effects models in cases of significant heterogeneity ( >50%). Safety analysis was performed based on adverse events reported in all studies.
RESULTS
Eleven studies (882 patients) were included in the meta-analysis. The pooled ORR was 28.1% (95% confidence interval [CI], 0.223-0.354), while the pooled DCR was 69.1% (95% CI, 0.631-0.756). ORRs were higher for tepotinib (44.7% [95% CI, 0.365-0.530]) and savolitinib (42.9% [95% CI, 0.311-0.553]) than for other types of MET inhibitors. Patients with NSCLC with exon 14 skipping exhibited higher ORRs (39.3% (95% CI, 0.296-0.522)) and DCRs (77.8% (95% CI, 0.714-0.847)) than those with MET protein overexpression or amplification. Intracranial response rate and intracranial disease control rates were 40.1% (95% CI, 0.289-0.556) and 95.4% (95% CI, 0.892-0.100), respectively. Adverse events were mild (grade 1 to 2) in 87.2% of patients. Common adverse events above grade 3 included lower extremity edema (3.5% [95% CI, 0.027-0.044]), alanine aminotransferase (ALT) elevation (2.4% [95% CI, 0.014-0.033]), and lipase elevation (2.2% [95% CI, 0.016-0.031]).
CONCLUSION
MET inhibitors, which exhibited a satisfactory safety profile in the current study, may become a new standard of care for addressing MET dysregulation in patients with advanced or metastatic NSCLC, and even in those with brain metastases, particularly tepotinib, savolitinib and capmatinib. Further randomized trials are required to establish standard predictive biomarkers for MET therapies and to compare the effects of different MET inhibitors in NSCLC with MET dysregulation.
PubMed: 36387098
DOI: 10.3389/fonc.2022.1013299