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International Journal of Molecular... May 2024Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as... (Meta-Analysis)
Meta-Analysis Review
Chemokines orchestrate many aspects of tumorigenic processes such as angiogenesis, apoptosis and metastatic spread, and related receptors are expressed on tumor cells as well as on inflammatory cells (e.g., tumor-infiltrating T cells, TILs) in the tumor microenvironment. Expressional changes of chemokines and their receptors in solid cancers are common and well known, especially in affecting colorectal cancer patient outcomes. Therefore, the aim of this current systematic review and meta-analysis was to classify chemokines as a prognostic biomarker in colorectal cancer patients. A systematic literature search was conducted in PubMed, CENTRAL and Web of Science. Information on the chemokine expression of 25 chemokines in colorectal cancer tissue and survival data of the patients were investigated. The hazard ratio of overall survival and disease-free survival with chemokine expression was examined. The risk of bias was analyzed using Quality in Prognosis Studies. Random effects meta-analysis was performed to determine the impact on overall respectively disease survival. For this purpose, the pooled hazard ratios (HR) and their 95% confidence intervals (CI) were used for calculation. Twenty-five chemokines were included, and the search revealed 5556 publications. A total of thirty-one publications were included in this systematic review and meta-analysis. Overexpression of chemokine receptor CXCR4 was associated with both a significantly reduced overall survival (HR = 2.70, 95%-CI: 1.57 to 4.66, = 0.0003) as well as disease-free survival (HR = 2.68, 95%-CI: 1.41 to 5.08, = 0.0026). All other chemokines showed either heterogeneous results or few studies were available. The overall risk of bias for CXCR4 was rated low. At the current level of evidence, this study demonstrates that CXCR4 overexpression in patients with colorectal cancer is associated with a significantly diminished overall as well as disease-free survival. Summed up, this systematic review and meta-analysis reveals CXCR4 as a promising prognostic biomarker. Nevertheless, more evidence is needed to evaluate CXCR4 and its antagonists serving as new therapeutic targets.
Topics: Humans; Colorectal Neoplasms; Prognosis; Biomarkers, Tumor; Chemokines; Receptors, CXCR4; Disease-Free Survival
PubMed: 38791414
DOI: 10.3390/ijms25105374 -
International Journal of Molecular... Mar 2024Cluster of differentiation 44 (CD44), a cell surface adhesion molecule overexpressed in cancer stem cells, has been implicated in chemoresistance. This scoping review,... (Review)
Review
Cluster of differentiation 44 (CD44), a cell surface adhesion molecule overexpressed in cancer stem cells, has been implicated in chemoresistance. This scoping review, following PRISMA-ScR guidelines, systematically identified and evaluated clinical studies on the impact of CD44 expression on chemotherapy treatment outcomes across various cancer types. The search encompassed PubMed (1985-2023) and SCOPUS (1936-2023) databases, yielding a total of 12,659 articles, of which 40 met the inclusion criteria and were included in the qualitative synthesis using a predefined data extraction table. Data collected included the cancer type, sample size, interventions, control, treatment outcome, study type, expression of CD44 variants and isoforms, and effect of CD44 on chemotherapy outcome. Most of the studies demonstrated an association between increased CD44 expression and negative chemotherapeutic outcomes such as shorter overall survival, increased tumor recurrence, and resistance to chemotherapy, indicating a potential role of CD44 upregulation in chemoresistance in cancer patients. However, a subset of studies also reported non-significant relationships or conflicting results. In summary, this scoping review highlighted the breadth of the available literature investigating the clinical association between CD44 and chemotherapeutic outcomes. Further research is required to elucidate this relationship to aid clinicians in managing CD44-positive cancer patients.
Topics: Humans; Drug Resistance, Neoplasm; Hyaluronan Receptors; Treatment Outcome
PubMed: 38542115
DOI: 10.3390/ijms25063141 -
Revista Espanola de Enfermedades... Mar 2024colorectal cancer (CRC) is the most common carcinoma worldwide, but a lack of effective prognostic markers limits clinical diagnosis and treatment. Yes-associated... (Meta-Analysis)
Meta-Analysis
BACKGROUND
colorectal cancer (CRC) is the most common carcinoma worldwide, but a lack of effective prognostic markers limits clinical diagnosis and treatment. Yes-associated protein 1 (YAP1) is an effector of the HIPPO-pathway, which plays a critical role in cancer development and prognosis, including CRC. However, previous reports have suggested that it plays a dual role in CRC.
METHODS
a meta-analysis using RevMan 5.4 and Stata 14.0 was performed to evaluate the relationship between YAP1 and clinical outcomes of CRC, after searching for eligible studies in the PubMed, Web of Science and Embase databases. Online datasets GEPIA and LOGpc were also used to calculate survival results and for comparison with the meta-analysis results. Besides, "DESeq" packages were used for the expression analysis of YAP1 from the TCGA dataset.
RESULTS
YAP1 was overexpressed in the cancer tissues when compared to normal tissues in patients with CRC from the TCGA database (p = 0.000164) and GEPIA database. A total of 10 studies involving 2305 patients from the literature were selected. Pooled HR indicated that overexpression of YAP1 was associated with poor clinical outcomes (HR = 1.70, 95 % CI: 1.28-2.26, p = 0.0003). Subgroup analysis showed a clear correlation between overexpression of YAP1 and worse survival rate in Chinese patients (HR = 1.94, 95 % CI: 1.40-2.69, p = 0.0001), nuclear YAP1 overexpression (HR = 2.07, 95 % CI: 1.29-3.31, p = 0.003), 60 months of follow-up (HR = 1.89, 95 % CI: 1.30-2.73, p = 0.0008), IHC test (HR = 1.65, 95 % CI: 1.17-2.33, p = 0.005), IHC combined with other tests (HR = 1.77, 95 % CI: 1.13-2.77, p = 0.01) and multivariate analysis (HR = 1.70, 95 % CI: 1.24-2.31, p = 0.0009). Nevertheless, disease-free survival (DFS) showed no significant results in the patients with CRC in our meta-analysis (HR = 1.38, 95 % CI: 0.51-3.75, p = 0.52) as well as in the GEPIA and LOGpc databases. Meanwhile, YAP1 overexpression was also significantly associated with worse overall survival (OS) in GSE17536, GSE40967, GSE29623 and GSE71187.
CONCLUSION
YAP1 overexpression is common in CRC tissues. Overexpression of YAP1 in CRC patients, particularly in the nucleus, might be related to shorter OS, maybe in the early stages. YAP1 could serve as a potential predictor of poor prognosis in CRC.
Topics: Humans; Prognosis; YAP-Signaling Proteins; Carcinoma; Databases, Factual; Colorectal Neoplasms
PubMed: 36177818
DOI: 10.17235/reed.2022.8472/2021 -
The Complex Role of Thrombin in Cancer and Metastasis: Focus on Interactions with the Immune System.Seminars in Thrombosis and Hemostasis Apr 2024Thrombin, a pleiotropic enzyme involved in coagulation, plays a crucial role in both procoagulant and anticoagulant pathways. Thrombin converts fibrinogen into fibrin,...
Thrombin, a pleiotropic enzyme involved in coagulation, plays a crucial role in both procoagulant and anticoagulant pathways. Thrombin converts fibrinogen into fibrin, initiates platelet activation, and promotes clot formation. Thrombin also activates anticoagulant pathways, indirectly inhibiting factors involved in coagulation. Tissue factor triggers thrombin generation, and the overexpression of thrombin in various cancers suggests that it is involved in tumor growth, angiogenesis, and metastasis. Increased thrombin generation has been observed in cancer patients, especially those with metastases. Thrombin exerts its effects through protease-activated receptors (PARs), particularly PAR-1 and PAR-2, which are involved in cancer progression, angiogenesis, and immunological responses. Thrombin-mediated signaling promotes angiogenesis by activating endothelial cells and platelets, thereby releasing proangiogenic factors. These functions of thrombin are well recognized and have been widely described. However, in recent years, intriguing new findings concerning the association between thrombin activity and cancer development have come to light, which justifies a review of this research. In particular, there is evidence that thrombin-mediated events interact with the immune system, and may regulate its response to tumor growth. It is also worth reevaluating the impact of thrombin on thrombocytes in conjunction with its multifaceted influence on tumor progression. Understanding the role of thrombin/PAR-mediated signaling in cancer and immunological responses is crucial, particularly in the context of developing immunotherapies. In this systematic review, we focus on the impact of the thrombin-related immune system response on cancer progression.
Topics: Humans; Thrombin; Endothelial Cells; Neoplasms; Receptor, PAR-1; Immune System; Anticoagulants
PubMed: 37984359
DOI: 10.1055/s-0043-1776875 -
Cell Journal Jan 2024Leucine-rich G protein-coupled receptor 5 () is a marker of cancer stem cells (CSCs) in various cancers. Based on different studies, conflicting reports exist on...
Clinical Implications and Prognostic Value of Leucine-Rich G Protein-Coupled Receptor 5 Expression as A Cancer Stem Cell Marker in Malignancies: A Systematic Review and Meta-Analysis.
Leucine-rich G protein-coupled receptor 5 () is a marker of cancer stem cells (CSCs) in various cancers. Based on different studies, conflicting reports exist on correlation between LGR5 expression and poor prognosis/ clinicopathological parameters in cancer patients. Therefore, our purpose in conducting this study was to investigate correlation between expression and outcomes of cancer patients under study through a systematic review and meta-analysis. Relevant articles were searched and collected using EMBASE, PubMed, Science Direct, and Scopus databases until December 21, 2022. This study was conducted to examine correlation between expression and different clinical outcomes, such as recurrence-free survival (RFS), disease-free survival (DFS), overall survival (OS), and clinicopathological characteristics of the included cancer patients. To achieve this, hazard ratios (HRs) with 95% confidence intervals (CIs) and odds ratios (ORs) with 95% CIs were used as statistical measures. A meta-analysis was conducted using STATA 12.0 software. Finally, 53 studies including 9523 patients met the inclusion criteria. Significantly, high-level expression of was related to poor prognosis in terms of OS, higher tumor stage, presence of distant metastasis, and presence of lymph node metastasis. It was discovered through subgroup analysis that several factors, including the study area, evaluation method, and type of cancer, can influence the correlation between expression and negative prognosis in cancer patients. According to the results of our study, overexpression was related to poor OS in cancer patients. In addition, clinicopathological data indicated an unfavorable prognosis in cancer patients with high expression. In conclusion, may serve as a potential prognostic marker for predicting survival in certain cancer types.
PubMed: 38351725
DOI: 10.22074/cellj.2023.2010157.1396 -
BMC Cancer Apr 2024The tripartite motif (TRIM) proteins have been reported to play crucial roles in various malignancies. However, the clinical significance of TRIM proteins in colorectal... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The tripartite motif (TRIM) proteins have been reported to play crucial roles in various malignancies. However, the clinical significance of TRIM proteins in colorectal cancer (CRC) remains controversial. This study aimed to evaluate the association between TRIM proteins and the clinicopathological features and survival outcomes in patients with CRC.
METHODS
We performed a meta-analysis to investigate whether TRIM is a prognostic factor in CRC. PubMed, Embase, Web of Science, CNKI and Weipu databases were searched to identify eligible studies that evaluated the association between TRIM proteins and overall survival (OS), as well as the clinicopathological features of patients with CRC. Hazard ratios (HR) or odds ratios (OR) with 95% confidence interval (CI) were derived and pooled using a fixed-effects model.
RESULTS
From inception to March 2023, we extracted study characteristics and prognostic data for each identified study. Twelve studies enrolling 1608 patients were eligible for inclusion. Data on OS and recurrence-free survival (RFS) were available for 12 and 2 studies, respectively. The pooled analysis results showed a significant correlation between the elevated TRIM proteins and shorter OS (HR = 2.42, 95% CI: 1.96-2.99) and worse RFS (HR = 2.51, 95% CI: 1.78-3.54) in patients with CRC. The combined ORs indicated that TRIM protein over-expression was significantly associated with advanced TNM stage (OR = 2.26, 95% CI: 1.25-4.10), deep tumor invasion (OR = 2.01, 95% CI: 1.04-3.88), lymph node metastasis (OR = 2.99, 95% CI: 2.19-4.09) and perineural invasion (OR = 1.95, 95% CI: 1.18-3.23).
CONCLUSIONS
Our findings suggest that TRIM proteins can predict tumor progression and poor prognosis in CRC. Therefore, TRIM proteins may be promising therapeutic targets for patients with CRC.
Topics: Humans; Colorectal Neoplasms; Tripartite Motif Proteins; Prognosis; Biomarkers, Tumor; Neoplasm Staging
PubMed: 38678238
DOI: 10.1186/s12885-024-12280-z -
Indian Journal of Otolaryngology and... Dec 2023Hypoxia-inducible factor-1α is a transcriptional protein that has been extensively researched in human cancers whose overexpression is found to be associated with...
Hypoxia-inducible factor-1α is a transcriptional protein that has been extensively researched in human cancers whose overexpression is found to be associated with unfavorable prognosis. Contemporary studies have proved its vital role in ameloblastoma by correlating its expression with the aggressiveness of the tumor. Therefore, an attempt was made to explore its significance in the malignant transformation and prognosis of ameloblastoma. The present systematic review aimed to understand the impact of HIF-1α in AMB which might lead to favorable outcomes in the treatment. An electronic search was carried out using PubMed, Scopus, Google scholar, Cochrane library, and EMBASE databases. Original articles from all languages involving HIF-1α in AMB were scrutinized by two independent authors. Data were compiled and tabulated in Microsoft Excel and the Risk of bias was analyzed using the JBI tool. Twelve eligible articles were included for the quantitative analysis comprising 305 cases of AMB in which HIF-1α expression was studied for various characteristics like pattern, intensity, and site of immunoexpression which were found to be increased with an increase in the aggressiveness of AMB. It was concluded that HIF-1α is proven to have a crucial role in the progression and aggressiveness of AMB. Extended research regarding the crucial role of HIF-1α in the initiation of tumors and therapies aiming at HIF-1α in AMB cases might show promising outcomes in the future.
PubMed: 37974737
DOI: 10.1007/s12070-023-03928-6 -
World Journal of Gastrointestinal... Apr 2024Heat shock proteins (HSPs) are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overexpressed...
BACKGROUND
Heat shock proteins (HSPs) are molecular chaperones that play an important role in cellular protection against stress events and have been reported to be overexpressed in many cancers. The prognostic significance of HSPs and their regulatory factors, such as heat shock factor 1 (HSF1) and CHIP, are poorly understood.
AIM
To investigate the relationship between HSP expression and prognosis in esophageal and esophagogastric cancer.
METHODS
A systematic review was conducted in accordance with PRISMA recommendations (PROSPERO: CRD42022370653), on Embase, PubMed, Cochrane, and LILACS. Cohort, case-control, and cross-sectional studies of patients with esophagus or esophagogastric cancer were included. HSP-positive patients were compared with HSP-negative, and the endpoints analyzed were lymph node metastasis, tumor depth, distant metastasis, and overall survival (OS). HSPs were stratified according to the HSP family, and the summary risk difference (RD) was calculated using a random-effect model.
RESULTS
The final selection comprised 27 studies, including esophageal squamous cell carcinoma (21), esophagogastric adenocarcinoma (5), and mixed neoplasms (1). The pooled sample size was 3465 patients. HSP40 and 60 were associated with a higher 3-year OS [HSP40: RD = 0.22; 95% confidence interval (CI): 0.09-0.35; HSP60: RD = 0.33; 95%CI: 0.17-0.50], while HSF1 was associated with a poor 3-year OS (RD = -0.22; 95%CI: -0.32 to -0.12). The other HSP families were not associated with long-term survival. HSF1 was associated with a higher probability of lymph node metastasis (RD = -0.16; 95%CI: -0.29 to -0.04). HSP40 was associated with a lower probability of lymph node dissemination (RD = 0.18; 95%CI: 0.03-0.33). The expression of other HSP families was not significantly related to tumor depth and lymph node or distant metastasis.
CONCLUSION
The expression levels of certain families of HSP, such as HSP40 and 60 and HSF1, are associated with long-term survival and lymph node dissemination in patients with esophageal and esophagogastric cancer.
PubMed: 38660660
DOI: 10.4251/wjgo.v16.i4.1578 -
British Journal of Cancer Mar 2024Recent studies have identified that low levels of some tumour suppressor microRNAs (miRNAs) in the blood contribute to tumour progression and poor outcomes in various...
BACKGROUND
Recent studies have identified that low levels of some tumour suppressor microRNAs (miRNAs) in the blood contribute to tumour progression and poor outcomes in various cancers. However, no study has proved these miRNAs are associated with cancer immune mechanisms.
METHODS
From a systematic review of the NCBI and miRNA databases, four tumour suppressor miRNA candidates were selected (miR-5193, miR-4443, miR-520h, miR-496) that putatively target programmed cell death ligand 1 (PD-L1).
RESULTS
Test-scale and large-scale analyses revealed that plasma levels of miR-5193 were significantly lower in gastric cancer (GC) patients than in healthy volunteers (HVs). Low plasma levels of miR-5193 were associated with advanced pathological stages and were an independent prognostic factor. Overexpression of miR-5193 in GC cells suppressed PD-L1 on the surface of GC cells, even with IFN-γ stimulation. In the coculture model of GC cells and T cells stimulated by anti-CD3/anti-CD28 beads, overexpression of miR-5193 increased anti-tumour activity of T cells by suppressing PD-L1 expression. Subcutaneous injection of miR-5193 also significantly enhanced the tumour-killing activity and trafficking of T cells in mice.
CONCLUSIONS
Low blood levels of miR-5193 are associated with GC progression and poor outcomes and could be a target of nucleic acid immunotherapy in GC patients.
Topics: Humans; Animals; Mice; Stomach Neoplasms; B7-H1 Antigen; MicroRNAs; Genes, Tumor Suppressor; Immunotherapy
PubMed: 38148376
DOI: 10.1038/s41416-023-02532-3 -
Seminars in Nuclear Medicine Mar 2024The gastrin-releasing peptide receptor (GRPR) is known to be overexpressed in breast cancer, making it a promising target for both imaging and therapy within a... (Review)
Review
The gastrin-releasing peptide receptor (GRPR) is known to be overexpressed in breast cancer, making it a promising target for both imaging and therapy within a theranostic framework. Various radioligands targeting GRPR have undergone investigation in preclinical and clinical studies related to breast cancer. This systematic scoping review aimed to assess the current evidence on GRPR-targeted radioligands for diagnostic and therapeutic applications in breast cancer. The methodology followed the PRISMA-ScR protocol. The literature search was conducted in September 2023 and encompassed MEDLINE, Embase, Cochrane, and Scopus databases. We included original peer-reviewed studies focused on breast cancer patients or in vivo breast cancer models. Two reviewers performed the study selection process independently. Data were extracted, synthesized, and categorized into preclinical and clinical studies, further subdivided based on radioligand properties. A total of 35 original studies were included in the review, with three of them evaluating therapeutic outcomes. The results indicated that GRPR-radioantagonists are superior to GRPR-agonists, exhibiting preferable in vivo stability, rapid, specific tumor targeting, and enhanced retention. Both preclinical and clinical evaluations demonstrated renal excretion and high uptake in normal GRPR-expressing tissue, primarily the pancreas. A significant positive correlation was observed between GRPR and estrogen-receptor expression. In the clinical setting, GRPR-radioligands effectively detected primary tumors and, to a lesser extent, lymph node metastases. Moreover, GRPR-targeted radioantagonists successfully identified distant metastases originating from various sites in advanced metastatic disease, strongly correlated with positive estrogen receptor expression. Preclinical therapeutic evaluation of GRPR-radioligands labeled with lutetium-177 showed promising tumor responses, and none of the studies reported any observed or measured side effects, indicating a safe profile. In conclusion, the evidence presented in this review indicates a preference for GRPR-targeted antagonists over agonists, owing to their superior kinetics and promising diagnostic potential. Clinical assessments suggested diagnostic value for GRPR-targeted theranostics in breast cancer patients, particularly those with high estrogen receptor expression. Nevertheless, in the therapeutic clinical context, paying attention to the radiation dose administered to the pancreas and kidneys is crucial.
Topics: Humans; Female; Receptors, Bombesin; Breast Neoplasms; Precision Medicine; Receptors, Estrogen
PubMed: 38342656
DOI: 10.1053/j.semnuclmed.2024.01.004