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British Journal of Cancer Mar 2014A significant proportion of squamous cell carcinomas of the oropharynx (OP-SCC) are related to human papillomavirus (HPV) infection and p16 overexpression. This subgroup... (Review)
Review
BACKGROUND
A significant proportion of squamous cell carcinomas of the oropharynx (OP-SCC) are related to human papillomavirus (HPV) infection and p16 overexpression. This subgroup proves better prognosis and survival but no evidence exists on the correlation between HPV and p16 overexpression based on diagnostic measures and definition of p16 overexpression. We evaluated means of p16 and HPV diagnostics, and quantified overexpression of p16 in HPV-positive and -negative OP-SCCs by mode of immunohistochemical staining of carcinoma cells.
METHODS
PubMed, Embase, and the Cochrane Library were searched from 1980 until October 2012. We applied the following inclusion criteria: a minimum of 20 cases of site-specific OP-SCCs, and HPV and p16 results present. Studies were categorised into three groups based on their definition of p16 overexpression: verbal definition, nuclear and cytoplasmatic staining between 5 and 69%, and ≥70% staining.
RESULTS
We identified 39 studies with available outcome data (n=3926): 22 studies (n=1980) used PCR, 6 studies (n=688) used ISH, and 11 studies (n=1258) used both PCR and ISH for HPV diagnostics. The methods showed similar HPV-positive results. Overall, 52.5% of the cases (n=2062) were HPV positive. As to p16 overexpression, 17 studies (n=1684) used a minimum of 5-69% staining, and 7 studies (n=764) used ≥70% staining. Fifteen studies (n=1478) referred to a verbal definition. Studies showed high heterogeneity in diagnostics of HPV and definition of p16. The correlation between HPV positivity and p16 overexpression proved best numerically in the group applying ≥70% staining for p16 overexpression. The group with verbal definitions had a significantly lower false-positive rate, but along with the group applying 5-69% staining showed a worse sensitivity compared with ≥70% staining.
CONCLUSIONS
There are substantial differences in how studies diagnose HPV and define p16 overexpression. Numerically, p16 staining is better to predict the presence of HPV (i.e. larger sensitivity), when the cutoff is set at ≥70% of cytoplasmatic and nuclear staining.
Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Squamous Cell; Cyclin-Dependent Kinase Inhibitor p16; Female; Genes, p16; Head and Neck Neoplasms; Humans; Male; Middle Aged; Neoplasm Proteins; Oropharyngeal Neoplasms; Papillomaviridae; Papillomavirus Infections; Prognosis; Risk Factors; Squamous Cell Carcinoma of Head and Neck; Young Adult
PubMed: 24518594
DOI: 10.1038/bjc.2014.42 -
BMJ Open Aug 2019Liver kinase B1 (LKB1) is considered a tumour suppressor that can control cell growth and metabolism. Whether LKB1 expression levels are related to clinicopathology and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
Liver kinase B1 (LKB1) is considered a tumour suppressor that can control cell growth and metabolism. Whether LKB1 expression levels are related to clinicopathology and prognosis is controversial. This review aimed to quantitatively examine the latest evidence on this question.
DESIGN
An updated systematic review and meta-analysis on the association between LKB1 expression and prognosis of patients with solid tumours were performed.
DATA SOURCES
Eligible studies were identified through literature searches from database establishment until 15 June 2018 in the following databases: Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure and Wan Fang databases.
ELIGIBILITY CRITERIA
The association between LKB1 expression and clinicopathological characteristics, overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) of patients with solid tumours were reported. Sufficient data were available to calculate the OR or HR and 95% CI.
DATA EXTRACTION AND SYNTHESIS
Relevant data were meta-analysed for OS, DFS, RFS and various clinical parameters.
RESULTS
The systematic review included 25 studies containing 6012 patients with solid tumours. Compared with patients with high LKB1 expression, patients with low expression showed significantly shorter OS in univariate analysis (HR=1.63, 95% CI 1.35 to 1.97, p<0.01) and multivariate analysis (HR=1.61, 95% CI 1.26 to 2.06, p<0.01). In contrast, the two groups showed similar DFS in univariate analysis (HR=1.49, 95% CI 0.73 to 3.01, p=0.27) as well as similar RFS in univariate analysis (HR=1.44, 95% CI 0.65 to 3.17, p=0.37) and multivariate analysis (HR=1.02, 95% CI 0.42 to 2.47, p=0.97). Patients with low LKB1 expression showed significantly worse tumour differentiation (OR=1.71, 95% CI 1.14 to 2.55, p<0.01), larger tumours (OR=1.68, 95% CI 1.24 to 2.27, p<0.01), earlier lymph node metastasis (OR=1.43, 95% CI 1.26 to 1.62, p<0.01) and more advanced tumour, node, metastases (TNM) stage (OR=1.80, 95% CI 1.56 to 2.07, p<0.01).
CONCLUSION
Low LKB1 expression predicts shorter OS, worse tumour differentiation, larger tumours, earlier lymph node metastasis and more advanced TNM stage. Low LKB1 expression may be a useful biomarker of poor clinicopathology and prognosis.
Topics: AMP-Activated Protein Kinase Kinases; Disease-Free Survival; Humans; Neoplasms; Prognosis; Protein Serine-Threonine Kinases; Survival Rate
PubMed: 31383697
DOI: 10.1136/bmjopen-2018-027185 -
BMC Cancer Nov 2016Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase responsible for regulating ribosomal biogenesis and protein synthesis. Dysregulation of mTOR... (Meta-Analysis)
Meta-Analysis Review
Clinicopathological and prognostic significance of mTOR and phosphorylated mTOR expression in patients with esophageal squamous cell carcinoma: a systematic review and meta-analysis.
BACKGROUND
Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase responsible for regulating ribosomal biogenesis and protein synthesis. Dysregulation of mTOR contributes to tumorigenesis, angiogenesis, cellular growth and metastasis but its roles in esophageal squamous cell carcinoma (ESCC) are controversial. Therefore, the objective of this study is to evaluate the prognostic and clinicopathological significance of mTOR/p-mTOR expression in ESCC.
METHODS
Literature retrieval was conducted by searching PubMed, EMBASE and the Web of Science for full-text papers that met our eligibility criteria. Odds ratio (OR) and hazard ratio (HR) with 95 % confidence interval (CI) served as the appropriate summarized statistics for assessments of clinicopathological and prognostic significance, respectively. Cochrane Q-test and I-statistic were adopted to estimate the heterogeneity level between studies. Potential publication bias was detected by Begg's test and Egger's test.
RESULTS
A total of 915 ESCC patients from nine original articles were included into this meta-analysis. The pooled analyses suggested that mTOR/p-mTOR expression was significantly correlated with the unfavorable outcomes of differentiation degree (OR: 2.63; 95 % CI: 1.71-4.05; P = 0.001), tumor invasion (OR: 1.48; 95 % CI: 1.02-2.13; P = 0.037), TNM stage (OR: 2.25; 95 % CI: 1.05-4.82; P = 0.037) and lymph node metastasis (OR: 1.82; 95 % CI: 1.06-3.11; P = 0.029), but had no significant relationship to the genders (OR: 0.81; 95 % CI: 0.50-1.32; P = 0.396). Moreover, mTOR/p-mTOR expression could independently predict the worse overall survival (HR: 2.04; 95 % CI: 1.58-2.62; P < 0.001), disease-free survival (HR: 2.39; 95 % CI: 1.64-3.49; P < 0.001) and cancer-specific survival (HR: 1.62; 95 % CI: 1.18-2.23; P = 0.003) of patients with ESCC. Such prognostic value of mTOR was not substantially altered by further subgroup analyses.
CONCLUSIONS
Positive expression of mTOR and p-mTOR was significantly associated with the unfavorable conditions on the depth of tumor invasion, TNM stage, differentiation degree and lymph node metastasis. mTOR and p-mTOR could serve as a valuable predictor for the poor prognosis of ESCC. More high-quality worldwide studies performing a multivariate analysis based on larger sample size are urgently required for further verifying and modifying our findings in the future.
Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Esophageal Neoplasms; Humans; Lymphatic Metastasis; Neoplasm Invasiveness; Phosphoproteins; Phosphorylation; Prognosis; Protein Processing, Post-Translational; Survival Analysis; TOR Serine-Threonine Kinases
PubMed: 27835987
DOI: 10.1186/s12885-016-2940-7 -
Epigenetics Sep 2022Adverse experiences in the perinatal period have been associated with the methylation of the human glucocorticoid receptor gene () and long-term diseases. We conducted a...
Adverse experiences in the perinatal period have been associated with the methylation of the human glucocorticoid receptor gene () and long-term diseases. We conducted a systematic review on the association between adversities in the perinatal period and DNA methylation in the 1 region of the gene in newborns. We explored the MEDLINE, Web of Science, Scopus, Scielo, and Lilacs databases without time or language limitations. Two independent reviewers performed the selection of articles and data extraction. A third participated in the methodological quality assessment and consensus meetings at all stages. Finally, ten studies were selected. Methodological quality was considered moderate in six and low in four. Methylation changes were reported in 41 of the 47 CpG sites of exon 1 . Six studies addressed maternal conditions during pregnancy: two reported methylation changes at the same sites (CpG 10, 13, 20, 21 and 47), and four at one or more sites from CpG 35 to 39. Four studies addressed neonatal parameters and morbidities: methylation changes at the same sites 4, 8, 10, 16, 25, and 35 were reported in two. Hypermethylation associated with stressful conditions prevailed. Hypomethylation was more often associated with protective conditions (maternal-foetal attachment during pregnancy, breast milk intake, higher birth weight or Apgar). In conclusion, methylation changes in several sites of the 1 region of the gene in newborns and very young infants were associated with perinatal stress, but more robust and comparable results are needed to corroborate site-specific associations.
Topics: DNA Methylation; Exons; Female; Humans; Infant; Infant, Newborn; Pregnancy; Protein Processing, Post-Translational; Receptors, Glucocorticoid
PubMed: 34519616
DOI: 10.1080/15592294.2021.1980691 -
PloS One 2018The cultivation of bananas and other plants is limited by environmental stresses caused by climate change. In order to recognize physiological, biochemical and molecular...
BACKGROUND
The cultivation of bananas and other plants is limited by environmental stresses caused by climate change. In order to recognize physiological, biochemical and molecular components indicated to confer tolerance to water stress in Musa spp. we present the first systematic review on the topic.
METHODS
A systematic literature review was conducted using four databases for academic research (Google Academic, Springer, CAPES Journal Portal and PubMed Central). In order to avoid publication bias, a previously established protocol and inclusion and exclusion criteria were used.
RESULTS
The drought tolerance response is genotype-dependent, therefore the most studied varieties are constituted by the "B" genome. Tolerant plants are capable of super-expressing genes related to reisistance and defense response, maintaining the osmotic equilibrium and elimination of free radicals. Furthermore, they have higher amounts of water content, chlorophyll levels, stomatic conductance and dry root matter, when compared to susceptible plants.
CONCLUSIONS
In recent years, few integrated studies on the effects of water stress on bananas have been carried out and none related to flood stress. Therefore, we highlight the need for new studies on the mechanisms of differentially expressed proteins in response to stress regulation, post-translational mechanisms and epigenetic inheritance in bananas.
Topics: Acclimatization; Chlorophyll; Droughts; Epigenesis, Genetic; Free Radicals; Gene Expression Regulation, Plant; Musa; Organism Hydration Status; Osmoregulation; Plant Proteins; Plant Stomata; Protein Processing, Post-Translational
PubMed: 30507957
DOI: 10.1371/journal.pone.0208052 -
Scandinavian Journal of Immunology Apr 2018The aberrant expression of interleukin-17 (IL-17) has been reported in primary Sjögren's syndrome (pSS). Abnormalities in IL-17 can promote the production of... (Meta-Analysis)
Meta-Analysis Review
The aberrant expression of interleukin-17 (IL-17) has been reported in primary Sjögren's syndrome (pSS). Abnormalities in IL-17 can promote the production of pro-inflammatory cytokines and aggravate autoimmune disorders. The aim of this study was to investigate alterations of IL-17 in patients with pSS and explore the correlation between IL-17 and disease severity. Eight databases were searched for original studies reporting the expression of IL-17 in patients with pSS and controls. Eligible reports were included in the pooled analysis, and subgroup evaluations were performed according to different types of controls and IL-17 measurement methods. Newcastle-Ottawa Scale criteria were used to assess the risk of bias of the included studies. In total, 45 articles are included in the meta-analysis. The expression of IL-17 is significantly increased in patients with pSS compared to controls. Furthermore, patients with pSS without immunosuppressive treatment show markedly higher IL-17 levels. In addition, patients with pSS with positive rheumatoid factors tend to express a higher level of IL-17 than patients with negative rheumatoid factors. Negative correlations between IL-17 levels and ocular parameters are also found in patients with pSS. The results are similar after adjustment by "trim and fill" methods. In conclusion, the expression of IL-17 is obviously increased in patients with pSS, especially among those without immunosuppressive treatment. In addition, IL-17 level correlates with the disease severity of pSS. These findings demonstrate the significance of IL-17 overexpression in patients with pSS and may provide insights for the development of therapeutic interventions targeting IL-17 for pSS.
Topics: Humans; Immunosuppression Therapy; Interleukin-17; Rheumatoid Factor; Saliva; Salivary Glands; Sjogren's Syndrome; Tears
PubMed: 29476557
DOI: 10.1111/sji.12649 -
Frontiers in Endocrinology 2021To explore the glycemic control [represented by glycated hemoglobin (HbA1c) concentrations] in children with diabetes mellitus (DM) in east China and middle- and...
Glycated Hemoglobin (HbA1c) Concentrations Among Children and Adolescents With Diabetes in Middle- and Low-Income Countries, 2010-2019: A Retrospective Chart Review and Systematic Review of Literature.
OBJECTIVES
To explore the glycemic control [represented by glycated hemoglobin (HbA1c) concentrations] in children with diabetes mellitus (DM) in east China and middle- and low-income countries, from 2010 to 2019.
METHODS
Retrospective data of children with DM from two hospital-based health records were reviewed. Data on HbA1c concentrations, hospitalization due to diabetic ketoacidosis, and patient demographics were collected and analyzed. A systematic review was subsequently performed to analyze publications that report HbA1c concentrations in patients aged <18 years. Patients' characteristics extracted from each publication were used to generate simulated individual data for pooled analysis. HbA1c estimates were derived from steady-state iterations.
RESULTS
Data of 843 diabetic children (aged 11.2 ± 3.9 years) with 2,658 HbA1c measures were retrieved from the two hospitals during the period 2010-2020. The duration of diabetes in the patients was 4.4 ± 2.8 years, and their HbA1c was 8.1 ± 2.2%. Patients who were internal migrants had significantly higher HbA1c concentration than resident patients (8.4 7.9%). The literature review yielded 1,164 publications, and the majority (74.1%) of patient data were published in high-income countries. The patient data extracted from these publications generated 486,416 HbA1c concentration estimates between 2005 and 2019. The average HbA1c concentration during the 15 years was 9.07 ± 2.15%. The mean HbA1c concentrations among children were 8.23, 8.73, 9.20, and 10.11% in high-income country (HIC), upper-middle income country (UMIC), lower-middle income country (LMIC), and low-income country (LIC) respectively. The mean rate of optimized glycemic control (HbA1c <7.5%) among children was 32.4, 27.5, 21.7, and 12.7% in HIC, UMIC, LMIC, and LIC, respectively.
CONCLUSIONS
The current study indicated that there is substantial room for improvement in glycemic control in children with DM worldwide, especially in middle- and low-income countries.
Topics: Adolescent; Child; Child, Preschool; China; Data Collection; Diabetes Mellitus; Diabetic Ketoacidosis; Electronic Health Records; Female; Glycated Hemoglobin; Hospitalization; Humans; Hypoglycemia; Infant; Infant, Newborn; Male; Models, Statistical; Retrospective Studies
PubMed: 33912137
DOI: 10.3389/fendo.2021.651589 -
Oncotarget Dec 2015CD133 is one of the most commonly used markers of cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. However, the... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
CD133 is one of the most commonly used markers of cancer stem cells (CSCs), which are characterized by their ability for self-renewal and tumorigenicity. However, the clinical and prognostic significance of CD133 in gastric cancer remains controversial. To clarify a precise determinant of the clinical significance of CD133, we conducted a systematic review and meta-analysis to elucidate the correlation of CD133 overexpression with prognosis and clinicopathological features of GC patients.
METHODS
A search in the Cochrane Library, PubMed, Medline, Web of Knowledge and Chinese CNKI, CBM (up to Jun 30, 2015) was performed using the following keywords gastric cancer, CD133, AC133, prominin-1, etc. Electronic searches were supplemented by hand searching reference lists, abstracts and proceedings from meetings. Outcomes included overall survival and various clinicopathological features. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the methodological quality of the included studies, and then RevMan 5.2.0 software was used for meta-analysis.
RESULTS
A total of 603 gastric cancer patients from 8 studies were included. The results of the meta-analyses showed that, there were significant differences of CD133 expression in the following comparisons: gastric cancer tissues vs. normal esophageal tissue (OR = 3.49, 95% CI [2.48, 490], P < 0.00001), lymph node metastasis vs. non-lymph node metastasis (OR = 2.75, 95% CI [1.99, 3.81], P < 0.00001), distant metastasis vs. non-distant metastasis (OR = 2.38, 95%CI [1.47, 3.85], P < 0.0004), clinical stages III~IV vs. clinical stages I~II (OR = 2.83, 95% CI [2.13, 3.76], P < 0.00001), as well as the accumulative 5-year overall survival rates of CD133-positive vs. CD133-negative patients (OR = 0.23, 95% CI [0.16, 0.33], P < 0.00001).
CONCLUSION
Overexpression of CD133 is associated with lymph node metastasis, distant metastasis, poor TNM stage. Additionally, CD133-positive gastric cancer patients had worse prognosis. Our results indicate that CD133 may be involved in the carcinogenesis of gastric cancer. Evaluation of cytoplasmic CD133 overexpression in gastric cancer tissue sections may be useful in the future as a novel prognostic factor. Nevertheless, due to the poor quality and small sample size of included trials, more well-designed multi-center randomized controlled trials should be performed.
Topics: AC133 Antigen; Antigens, CD; Female; Glycoproteins; Humans; Immunohistochemistry; Male; Neoplasm Metastasis; Neoplasm Staging; Peptides; Prognosis; Stomach Neoplasms; Survival Analysis
PubMed: 26503471
DOI: 10.18632/oncotarget.5714 -
BioMed Research International 2014The protooncogene PCPH was recently identified as being the ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5). This protooncogene is converted into an oncogene... (Review)
Review
The protooncogene PCPH was recently identified as being the ectonucleoside triphosphate diphosphohydrolase 5 (ENTPD5). This protooncogene is converted into an oncogene by a single base pair deletion, resulting in frame change and producing a premature stop codon, leading to a mutated protein (mt-PCPH) with only 27 kDa, which is much smaller than the original 47 kDa protein. Overexpression of the PCPH as well as the mutated PCPH increases the cellular resistance to stress and apoptosis. This is intriguing considering that the active form, that is, the oncogene, is the mutated PCPH. Several studies analyzed the expression of NTPDase5/mt-PCPH in a wide range of tumor cells and evaluated its role and mechanisms in cancer and other pathogenic processes. The main point of this review is to integrate the findings and proposed theories about the role played by NTPDase5/mt-PCPH in cancer progression, considering that these proteins have been suggested as potential early diagnostic tools and therapy targets.
Topics: Apoptosis; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Molecular Targeted Therapy; Neoplasm Staging; Neoplasms; Oncogene Proteins; Pyrophosphatases; Sequence Deletion
PubMed: 25045656
DOI: 10.1155/2014/123010 -
BioMed Research International 2015Metastasis associated in colon cancer 1 (MACC1), a newly identified oncogene, has been associated with poor survival of cancer patients by multiple studies. However, the... (Meta-Analysis)
Meta-Analysis Review
Metastasis associated in colon cancer 1 (MACC1), a newly identified oncogene, has been associated with poor survival of cancer patients by multiple studies. However, the prognostic value of MACC1 in digestive system neoplasms needs systematic evidence to verify. Therefore, we aimed to provide further evidence on this topic by systematic review and meta-analysis. Literature search was conducted in multiple databases and eligible studies analyzing survival data and MACC1 expression were included for meta-analysis. Hazard ratio (HR) for clinical outcome was chosen as an effect measure of interest. According to our inclusion criteria, 18 studies with a total of 2,948 patients were identified. Pooled HRs indicated that high MACC1 expression significantly correlates with poorer OS in patients with digestive system neoplasms (HR = 1.94; 95% CI: 1.49-2.53) as well as poorer relapse-free survival (HR = 1.94, 95% CI: 1.33-2.82). The results of subgroup studies categorized by methodology, anatomic structure, and cancer subtype for pooled OS were all consistent with the overall pooled HR for OS as well. No publication bias was detected according to test of funnel plot asymmetry and Egger's test. In conclusion, high MACC1 expression may serve as a prognostic biomarker to guide individualized management in clinical practice for digestive system neoplasms.
Topics: Biomarkers, Tumor; Digestive System Neoplasms; Disease-Free Survival; Gene Expression Regulation, Neoplastic; Humans; Neoplasm Metastasis; Neoplasm Recurrence, Local; Prognosis; Trans-Activators; Transcription Factors
PubMed: 26090393
DOI: 10.1155/2015/252043