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Frontiers in Oncology 2022Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal bone-marrow diseases with ineffective hematopoiesis resulting in cytopenias and morphologic dysplasia...
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal bone-marrow diseases with ineffective hematopoiesis resulting in cytopenias and morphologic dysplasia of hematopoietic cells. MDS carry a wide spectrum of genetic abnormalities, ranging from chromosomal abnormalities such as deletions/additions, to recurrent mutations affecting the spliceosome, epigenetic modifiers, or transcription factors. As opposed to AML, research in MDS has been hindered by the lack of preclinical models that faithfully replicate the complexity of the disease and capture the heterogeneity. The complex molecular landscape of the disease poses a unique challenge when creating transgenic mouse-models. In addition, primary MDS cells are difficult to manipulate limiting studies and resulting in a paucity of cell lines and patient derived xenograft models. In recent years, progress has been made in the development of both transgenic and xenograft murine models advancing our understanding of individual contributors to MDS pathology as well as the complex primary interplay of genetic and microenvironment aberrations. We here present a comprehensive review of these transgenic and xenograft models for MDS and future directions.
PubMed: 35372085
DOI: 10.3389/fonc.2022.815037 -
Medicine Dec 2021DNA damage is a fundamental process that plays a considerable role in generating protein diversity. FANCI, loaded on the altered chromatin, plays a vital role in DNA... (Meta-Analysis)
Meta-Analysis
BACKGROUND
DNA damage is a fundamental process that plays a considerable role in generating protein diversity. FANCI, loaded on the altered chromatin, plays a vital role in DNA damage. Abnormal FANCI expression is potentially associated with carcinogenesis.However, the biological role of FANCI in cervical cancer is yet to be determined.
METHODS
We analyzed FANCI expression via multiple gene expression databases. Genes co-expressed with FANCI and its regulators were identified using LinkedOmics. The correlations between FANCI and cancer immune infiltrates were investigated via Tumor Immune Estimation Resource (TIMER).
RESULTS
FANCI was found upregulated with amplification in tumor tissues of multiple cervical cancer cohorts. High FANCI expression was associated with poorer overall survival (OS). Functional network analysis suggested that FANCI regulates spliceosome, DNA replication, and cell cycle signaling via pathways involving several cancer-related kinases and the E2F family. In additional, FANCI expression was positively correlated with infiltrating levels of CD4+ T and CD8+ T cells, and neutrophils. FANCI expression also showed strong correlations with diverse immune marker sets in cervical cancer.
CONCLUSION
These findings suggested that FANCI is correlated with prognosis of and immune infiltration in cervical cancer, laying a foundation for further study of the immune regulatory role of FANCI in cervical cancer.
Topics: Biomarkers, Tumor; CD8-Positive T-Lymphocytes; Fanconi Anemia Complementation Group Proteins; Female; Gene Expression Regulation; Humans; Lymphocytes, Tumor-Infiltrating; Prognosis; Uterine Cervical Neoplasms
PubMed: 34941027
DOI: 10.1097/MD.0000000000027690 -
Medicine Aug 2021Plenty of studies have showed matrix metalloproteinase 14 (MMP14) expression might be associated with the prognosis of gastric cancer (GC). However, no definite... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Plenty of studies have showed matrix metalloproteinase 14 (MMP14) expression might be associated with the prognosis of gastric cancer (GC). However, no definite conclusion has been obtained for the contradictory results.
METHODS
We searched PubMed, Web of science, Embase, and Cochrane library for eligible studies. The association between MMP14 expression and prognostic outcomes of GC was evaluated. Hazard ratio (HR) and 95% confidence interval (CI) were integrated to show the effect of MMP14 expression on the overall survival (OS) or recurrence-free survival (RFS). Data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) was used to validate the association of MMP14 expression with OS or RFS in GC. A brief bioinformatics analysis was also performed to determine the prognostic role of MMP14 expression in GC.
RESULTS
High MMP14 expression was associated with shorter OS compared to low MMP14 expression in GC (HR = 1.95, P < .01). Patients with high MMP14 expression tended to have worse differentiation (P = .03), deeper tumor invasion (P < .01), earlier lymph node metastasis (P < .01), earlier distant metastasis (P < .01) and more advanced clinical stage (P < .01) compared to those with low MMP14 expression. The data from TCGA and GEO showed MMP14 was overexpressed in tumor tissues compared to normal tissues (P < .05), and high MMP14 expression was significantly related to shorter OS (HR = 1.70, 95% CI = 1.32-2.20, P < .01) and RFS (HR = 1.45, 95% CI = 1.15-1.83, P < .01) compared to low MMP14 expression in GC. Expression of MMP14 was linked to functional networks involving the biological process, metabolic process, response to stimulus, cell communication and so on. Functional network analysis suggested that MMP14 regulated the protein digestion and absorption, extracellular matrix receptor interaction, focal adhesion, ribosome, spliceosome, and so on.
CONCLUSION
High MMP14 expression was associated with worse prognosis of GC compared to low MMP14 expression. MMP14 expression could serve as a prognostic factor and potential therapeutic target of GC.
Topics: Biomarkers, Tumor; DNA, Neoplasm; Disease Progression; Gene Expression Regulation, Neoplastic; Humans; Matrix Metalloproteinase 14; Prognosis; Stomach Neoplasms
PubMed: 34397871
DOI: 10.1097/MD.0000000000026545