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Viruses Mar 2022During HIV/SIV infection, the upregulation of immune checkpoint (IC) markers, programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4... (Review)
Review
During HIV/SIV infection, the upregulation of immune checkpoint (IC) markers, programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), T cell immunoglobulin and ITIM domain (TIGIT), lymphocyte-activation gene-3 (LAG-3), T cell immunoglobulin and mucin domain-3 (Tim-3), CD160, 2B4 (CD244), and V-domain Ig suppressor of T cell activation (VISTA), can lead to chronic T cell exhaustion. These ICs play predominant roles in regulating the progression of HIV/SIV infection by mediating T cell responses as well as enriching latent viral reservoirs. It has been demonstrated that enhanced expression of ICs on CD4 and CD8 T cells could inhibit cell proliferation and cytokine production. Overexpression of ICs on CD4 T cells could also format and prolong HIV/SIV persistence. IC blockers have shown promising clinical results in HIV therapy, implying that targeting ICs may optimize antiretroviral therapy in the context of HIV suppression. Here, we systematically review the expression profile, biological regulation, and therapeutic efficacy of targeted immune checkpoints in HIV/SIV infection.
Topics: Animals; CD8-Positive T-Lymphocytes; Disease Progression; HIV Infections; Humans; Immunoglobulins; Lymphocyte Activation; Simian Acquired Immunodeficiency Syndrome; Simian Immunodeficiency Virus
PubMed: 35336991
DOI: 10.3390/v14030581 -
Critical Reviews in Oncology/hematology Mar 2021Hypoxia is a characteristic of many solid tumours and results in an increase in expression of HIF-1α. Many studies have investigated the prognostic value of HIF-1α... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Hypoxia is a characteristic of many solid tumours and results in an increase in expression of HIF-1α. Many studies have investigated the prognostic value of HIF-1α expression in breast cancer (BC), however, the prognostic value remains unclear. Therefore, a systematic review and meta-analysis was undertaken to determine the prognostic value of HIF-1α in BC patients.
METHODS
The electronic databases PubMed and Web of science were systematically searched to identify relevant papers. The clinical outcomes included disease-free survival (DFS), recurrence-free survival (RFS) and overall survival (OS) in BC patients. Review Manager version 5.4 was employed to analysis data from 30 eligible studies (containing 6201patients).
RESULTS
High expression of HIF-1α was associated with poorer DFS and OS. There was an effect of survival analysis, study region, antibodies used, scoring and threshold methods on HIF-1α expression.
CONCLUSION
HIF-1α overexpression was significantly associated with poorer DFS and OS in breast cancer patients.
Topics: Biomarkers, Tumor; Breast Neoplasms; Disease-Free Survival; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Prognosis; Survival Analysis
PubMed: 33482350
DOI: 10.1016/j.critrevonc.2021.103231 -
Biomolecules Jul 2021Oral squamous cell carcinoma (OSCC) is a prevalent malignancy associated with a poor prognosis. The Warburg effect can be observed in OSCCs, with tumours requiring a... (Review)
Review
Oral squamous cell carcinoma (OSCC) is a prevalent malignancy associated with a poor prognosis. The Warburg effect can be observed in OSCCs, with tumours requiring a robust glucose supply. Glucose transporters (GLUTs) and sodium-glucose co-transporters (SGLTs) are overexpressed in multiple malignancies, and are correlated with treatment resistance, clinical factors, and poor overall survival (OS). We conducted a systematic review to evaluate the differences in GLUT/SGLT expression between OSCC and normal oral keratinocytes (NOK), as well as their role in the pathophysiology and prognosis of OSCC. A total of 85 studies were included after screening 781 papers. GLUT-1 is regularly expressed in OSCC and was found to be overexpressed in comparison to NOK, with high expression correlated to tumour stage, treatment resistance, and poor prognosis. No clear association was found between GLUT-1 and tumour grade, metastasis, and fluorodeoxyglucose (FDG) uptake. GLUT-3 was less thoroughly studied but could be detected in most samples and is generally overexpressed compared to NOK. GLUT-3 negatively correlated with overall survival (OS), but there was insufficient data for correlations with other clinical factors. Expression of GLUT-2/GLUT-4/GLUT-8/GLUT-13/SGLT-1/SGLT-2 was only evaluated in a small number of studies with no significant differences detected. GLUTs 7 and 14 have never been evaluated in OSCC. In conclusion, the data demonstrates that GLUT-1 and GLUT-3 have a role in the pathophysiology of OSCC and represent valuable biomarkers to aid OSCC diagnosis and prognostication. Other GLUTs are comparatively understudied and should be further analysed because they may hold promise to improve patient care.
Topics: Animals; Biomarkers, Tumor; Cell Line; Glucose Transport Proteins, Facilitative; Humans; Mice; Mouth Neoplasms; Prognosis; Squamous Cell Carcinoma of Head and Neck
PubMed: 34439735
DOI: 10.3390/biom11081070 -
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 -
Cancer Metastasis Reviews Mar 2017Human epidermal growth factor receptor 2 (HER2) overexpression and amplification have been reported as predictive markers for HER2-targeted therapy in breast and gastric... (Meta-Analysis)
Meta-Analysis Review
Human epidermal growth factor receptor 2 (HER2) overexpression and amplification have been reported as predictive markers for HER2-targeted therapy in breast and gastric cancer, whereas human epidermal growth factor receptor 3 (HER3) is emerging as a potential resistance factor. The aim of this study was to perform a systematic review and meta-analysis of the HER2 and HER3 overexpression and amplification in biliary tract cancers (BTCs). An electronic search of MEDLINE, American Society of Clinical Oncology (ASCO), European Society of Medical Oncology Congress (ESMO), and American Association for Cancer Research (AACR) was performed to identify studies reporting HER2 and/or HER3 membrane protein expression by immunohistochemistry (IHC) and/or gene amplification by in situ hybridization (ISH) in BTCs. Studies were classified as "high quality" (HQ) if IHC overexpression was defined as presence of moderate/strong staining or "low quality" (LQ) where "any" expression was considered positive. Of 440 studies screened, 40 met the inclusion criteria. Globally, HER2 expression rate was 26.5 % (95 % CI 18.9-34.1 %). When HQ studies were analyzed (n = 27 studies), extrahepatic BTCs showed a higher HER2 overexpression rate compared to intrahepatic cholangiocarcinoma: 19.9 % (95 % CI 12.8-27.1 %) vs. 4.8 % (95 % CI 0-14.5 %), respectively, p value 0.0049. HER2 amplification rate was higher in patients selected by HER2 overexpression compared to "unselected" patients: 57.6 % (95 % CI 16.2-99 %) vs. 17.9 % (95 % CI 0.1-35.4 %), respectively, p value 0.0072. HER3 overexpression (4/4 HQ studies) and amplification rates were 27.9 % (95 % CI 9.7-46.1 %) and 26.5 % (one study), respectively. Up to 20 % of extrahepatic BTCs appear to be HER2 overexpressed; of these, close to 60 % appear to be HER2 amplified, while HER3 is overexpressed or amplified in about 25 % of patients. Clinical relevance for targeted therapy should be tested in prospective clinical trials.
Topics: Biliary Tract Neoplasms; Humans; Metabolic Networks and Pathways; Receptor, ErbB-2; Receptor, ErbB-3
PubMed: 27981460
DOI: 10.1007/s10555-016-9645-x -
Virchows Archiv : An International... Apr 2015Despite improvements in both diagnostic and therapeutic strategies, the prognosis of oral squamous cell carcinoma (OSCC) has not changed significantly over the last... (Meta-Analysis)
Meta-Analysis Review
The diagnostic value of 11q13 amplification and protein expression in the detection of nodal metastasis from oral squamous cell carcinoma: a systematic review and meta-analysis.
Despite improvements in both diagnostic and therapeutic strategies, the prognosis of oral squamous cell carcinoma (OSCC) has not changed significantly over the last decades. Prognosis of OSCC particularly depends on the presence of nodal metastasis in the neck. Therefore, proper determination of the nodal status is pivotal for appropriate treatment. Unfortunately, current available imaging techniques (magnetic resonance imaging or ultrasound even with fine needle aspiration of suspected lymph nodes (LNs)) fail to detect occult nodal disease accurately. Clinicians in head and neck oncology urgently need new diagnostic tools to reliably determine the presence of nodal metastasis of the neck. Gain of the chromosomal region 11q13 is one of the most prominent genetic alterations in head and neck cancer and is associated with poor prognosis and metastasis. The aim of this systematic review and meta-analysis was to determine the diagnostic value of either 11q13 amplification or amplification/protein overexpression of individual genes located on 11q13 to detect nodal metastasis in OSCC. A search was conducted in Pubmed, EMBASE, and Cochrane, and 947 unique citations were retrieved. Two researchers independently screened all articles and only 18 were found to meet our inclusion criteria and were considered of sufficient quality for meta-analysis. Pooled results of those show that both amplification of CCND1 and protein overexpression of cyclin D1 significantly correlate with lymph node metastasis (LNM) in OSCC. In addition, amplification of CCND1 shows a negative predictive value of 80 % in the detection of LNM in early stage OSCCs which are clinically lymph node negative although this evidence is sparse and should be validated in a larger homogeneous cohort of T1-2 OSCC.
Topics: Biomarkers, Tumor; Carcinoma, Squamous Cell; Chromosomes, Human, Pair 11; Cyclin D1; Gene Amplification; Humans; Lymphatic Metastasis; Mouth Neoplasms
PubMed: 25663615
DOI: 10.1007/s00428-015-1719-6 -
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 -
International Journal of Surgery... Aug 2018Hepatocellular carcinoma (HCC) is one of most common causes for cancer-related death around the world. Epithelial cell adhesion molecule (EpCAM) is established as a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatocellular carcinoma (HCC) is one of most common causes for cancer-related death around the world. Epithelial cell adhesion molecule (EpCAM) is established as a vital prognostic factor for the human malignant tumors. However, the potential role of EpCAM in HCC has largely remained elusive. Herein we aimed to gain insight into the clinicopathological and prognostic role of EpCAM in HCC.
METHODS AND MATERIALS
The PubMed, Web of Science, EMBASE and SCOPUS databases were systematically searched from their inception up to 5 December 4, 2017. The hazard ratio (HR) and odds ratio (OR) were respectively used as the effect size to explore the associations between EpCAM expression and the prognosis and clinicopathological features in HCC patients.
RESULTS
Sixteen studies recruiting 2488 HCC patients were included in the meta-analysis, of which the publication year ranging from 2011 to 2017. As a result, the pooled HR of 1.634 indicated that higher EpCAM expression was significantly associated with the shorter overall survival (OS) periods (95%CIs: 1.151-2.320; Z = 2.740, P = 0.006). Next, a meta-analysis of disease-free survival (DFS) was performed for the ten studies. Consequently, for the p-value less than 0.05 for the combined HR, the overexpression of EpCAM was significantly correlated with poorer DFS. Next, the results derived from our study suggest that the overexpression of EpCAM is associated with the clinicopathological features of HCC, including poorer tumor differentiation and high alpha-fetoprotein (AFP) levels.
CONCLUSION
The results derived from our study suggest that the overexpression of EpCAM is associated with the clinicopathological features of HCC, including poorer differentiation and high AFP levels. More importantly, overexpression of EpCAM was confirmed as the unfavorable predictor for the shorter OS and DFS for HCC patients.
Topics: Biomarkers, Tumor; Carcinoma, Hepatocellular; Disease-Free Survival; Epithelial Cell Adhesion Molecule; Female; Humans; Liver Neoplasms; Neoplasm Proteins; Odds Ratio; Prognosis; Proportional Hazards Models
PubMed: 29936198
DOI: 10.1016/j.ijsu.2018.06.025 -
Oncotarget Jul 2017The special AT-rich sequence-binding proteins 1 (SATB1) is a major regulator involved in cell differentiation. It has been shown that SATB1 acts as an oncogenic... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The special AT-rich sequence-binding proteins 1 (SATB1) is a major regulator involved in cell differentiation. It has been shown that SATB1 acts as an oncogenic regulator. The clinical and prognostic significance of SATB1 in gastrointestinal cancer remains controversial. The purpose of this study is to conduct a systematic review and meta-analysis to elucidate the impact of SATB1 in gastrointestinal cancer.
RESULTS
A total of 3174 gastrointestinal cancer patients from 15 studies were included. The correlation between SATB1 expression and OS or RFS was investigated in 12 and 5 studies respectively. The results of meta-analysis showed that SATB1 overexpression is inversely correlated with OS (combined HR: 1.79, p = 0.0003) and RFS (combined HR: 2.46, p < 0.0001). In subgroup analysis, SATB1 expression is significantly correlated with poor prognosis in gastrointestinal cancer in Asian population. SATB1 expression is associated with stage, invasion depth, lymph node metastasis and distant metastasis.
METHODOLOGY
Published studies with data on overall survival (OS) and/or relapse free survival (RFS) and SATB1 expression were searched from Cochrane Library, PubMed and Embase (up to Dec 30, 2016). The outcome measurement is hazard ratio (HR) for OS or RFS related with SATB1 expression. Two reviewers independently screened the literatures, extracted the data and performed meta-analysis using RevMan 5.3.0 software. The combined HRs were calculated by fixed- or random-effect models.
CONCLUSIONS
The results of this meta-analysis suggest that SATB1 overexpression is related to advanced stage, lymph node metastasis and distant metastasis. SATB1 overexpression is a marker indicating poor prognosis in gastrointestinal cancer.
Topics: Asian People; Biomarkers, Tumor; Gastrointestinal Neoplasms; Gene Expression; Humans; Matrix Attachment Region Binding Proteins; Neoplasm Staging; Odds Ratio; Prognosis; Proportional Hazards Models; Publication Bias; White People
PubMed: 28430598
DOI: 10.18632/oncotarget.16867 -
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