CD147/EMMPRIN (extracellular matrix metalloproteinase inducer) plays an important role in tumor progression and a number of studies have suggested that it is an indicator of tumor prognosis. This current meta-analysis systematically reevaluated the predictive potential of CD147/EMMPRIN in various cancers. We searched PubMed and Embase databases to screen the literature. Fixed-effect and random-effect meta-analytical techniques were used to correlate CD147 expression with outcome measures. A total of 53 studies that included 68 datasets were eligible for inclusion in the final analysis. We found a significant association between CD147/EMMPRIN overexpression and adverse tumor outcomes, such as overall survival, disease-specific survival, progression-free survival, metastasis-free survival or recurrence-free survival, irrespective of the model analysis. In addition, CD147/EMMPRIN overexpression predicted a high risk for chemotherapy drugs resistance. CD147/EMMPRIN is a central player in tumor progression and predicts a poor prognosis, including in patients who have received chemo-radiotherapy. Our results provide the evidence that CD147/EMMPRIN could be a potential therapeutic target for cancers.
GTSE1 is well correlated with tumor progression; however, little is known regarding its role in liver cancer prognosis. By analyzing the hepatocellular carcinoma (HCC) datasets in GEO and TCGA databases, we showed that high expression of GTSE1 was correlated with advanced pathologic stage and poor prognosis of HCC patients. To investigate underlying molecular mechanism, we generated GTSE1 knockdown HCC cell line and explored the effects of GTSE1 deficiency in cell growth. Between GTSE1 knockdown and wild-type HCC cells, we identified 979 differentially expressed genes (520 downregulated and 459 upregulated genes) in the analysis of microarray-based gene expression profiling. Functional enrichment analysis of DEGs suggested that S phase was dysregulated without GTSE1 expression, which was further verified from flow cytometry analysis. Moreover, three other DEGs: CDC20, PCNA, and MCM6, were also found contributing to GTSE1-related cell cycle arrest and to be associated with poor overall survival of HCC patients. In conclusion, GTSE1, together with CDC20, PCNA, and MCM6, may synergistically promote adverse prognosis in HCC by activating cell cycle. Genes like GTSE1, CDC20, PCNA, and MCM6 may be promising prognostic molecular biomarkers in liver cancer.
Endometriosis is a polygenic/multifactorial disease caused by interactions between multiple genes and the environment. Findings from studies evaluating the association between the glutathione S-transferase (GST) M1/T1 null genotype and susceptibility to endometriosis are inconsistent. This meta-analysis updated and reevaluated the possible associations between GSTM1, GSTT1 and combined GSTM1/GSTT1 (null genotype versus wild-type) gene polymorphisms and susceptibility to endometriosis. The PubMed, Embase and Chinese BioMedical Literature databases and Google Scholar were searched for case-control genetic association studies on GSTM1/GSTT1 (null genotype versus wild-type) gene polymorphisms and endometriosis in comparison with non-endometriosis or healthy controls. Fixed-effect and random-effect meta-analytical techniques were conducted for the outcome measure and subgroup analyses. The meta-analysis demonstrated significant associations between the GSTM1 [odds ratio (OR)=1.56; 95% confidence interval (CI): 1.25–1.95; P<0.0001), GSTT1 (OR=1.31; 95% CI: 1.02–1.68; P=0.037) and GSTM1/GSTT1 (OR=1.68; 95% CI: 1.29–2.17; P<0.0001) null genotypes and increased risk for endometriosis. The results suggest that the GSTM1, GSTT1, and combined GSTM1/GSTT1 null genotypes increase susceptibility to endometriosis. Additional well-designed studies and precise analyses are warranted to confirm these findings.
Hepatocellular carcinoma (HCC) is the most common gastrointestinal tumor with a poor prognosis, which is associated with poor differentiation of tumor cells. However, the potential value of cell differentiation-related molecules in predicting the benefit and prognosis of immune checkpoint inhibitors (ICI) therapy remains unknown. Herein, to investigate the differentiation trajectory of HCC cells and their clinical significance, a differentiation-related gene prognostic index (DRGPI) based on HCC differentiation-related genes (HDRGs) was constructed to elucidate the immune characteristics and therapeutic benefits of ICI in the HCC subgroup defined by DRGPI. Single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data from four HCC samples were integrated for bioinformatics analysis. Then, PON1, ADH4, SQSTM1, HSP90AA1, and STMN1 were screened out to construct a DRGPI. More intriguingly, RT-qPCR validation of the expression of these genes yielded consistent results with the TCGA database. Next, the risk scoring (RS) constructed based on DRGPI suggested that the overall survival (OS) of the DRGPI-high patients was significantly worse than that of the DRGPI-low patients. A nomogram was constructed based on DRGPI-RS and clinical characteristics, which showed strong predictive performance and high accuracy. The comprehensive results indicated that a low DRGPI score was associated with low TP53 mutation rates, high CD8 T cell infiltration, and more benefit from ICI therapy. Homoplastically, the high DRGPI score reflected the opposite results. Taken together, our study highlights the significance of HCC cell differentiation in predicting prognosis, indicating immune characteristics, and understanding the therapeutic benefits of ICI, and suggests that DRGPI is a valuable prognostic biomarker for HCC.
Pancreatic adenocarcinoma (PAAD) is characterized by high malignancy, frequent metastasis, and recurrence with an unfavorable prognosis. This study is aimed at constructing a prognostic model for tumor-infiltrating immune cells and a competing endogenous RNA (ceRNA) network in PAAD and analyzing susceptibilities of chemotherapy and immunotherapy of PAAD. Gene expression profiles and clinical information of PAAD were downloaded from The Cancer Genome Atlas (TCGA) database and divided into the tumor group and the normal group. A total of five PAAD survival-related key genes in the ceRNA network and three survival-related immune infiltrating cells were uncovered, and two survival risk models and nomograms were constructed. The efficiency and performance of the two models were verified using multi-index area under the curve analysis at different time points, decision curve analysis, and calibration curves. Co-expression analysis showed that LRRC1, MIR600HG, and RNF166 in the ceRNA network and tumor-infiltrating immune cells including CD8 T cells and M1 macrophages were likely related to the PAAD prognosis, and the expression of key ceRNA-related genes was experimently validated in tissues and cell lines by RT-qPCR. Patients with low risk scores for key genes in the ceRNA network displayed a positive response to anti-programmed death-1 (PD-1) treatment and greater sensitivity to chemotherapeutic drugs such as docetaxel, lapatinib, and paclitaxel. More importantly, our results suggested that the IC50 values of gemcitabine in PAAD were not significantly different between the high and low risk groups. The expression levels of immune checkpoints were significantly different in the high-risk and low-risk groups. The prognostic model, nomogram, and drug analysis may provide an essential reference for PAAD patient management in the clinic.
Wilms' tumor (WT) is the most typical basic renal tumor in children and is associated with a high recurrence rate and improper diagnosis. Long noncoding RNAs (lncRNAs) play important roles in WT development. However, the impact of the OSTM1 antisense RNA 1 (OSTM1-AS1) lncRNA on WT remains largely unexplored. Differential expression of OSTM1-AS1, miR-514a-3p and maternal embryonic leucine zipper kinase (MELK) in mice with WT cells was assessed via quantitative reverse transcription-PCR and western blotting. Changes in the proliferation, migration and apoptosis of WT cells after OSTM1-AS1, miR-514a-3p or MELK knockdown were assessed using the cell counting kit-8, Transwell and caspase-3 activity assays, respectively. Additionally, the tumorigenicity of WT cells after OSTM1-AS1 knockdown in vivo was analyzed using a xenograft tumor assay. The association among OSTM1-AS1, MELK and miR-514a-3p was confirmed using the RNA binding protein immunoprecipitation and luciferase reporter assays. OSTM1-AS1 and MELK were upregulated in WT cells, whereas miR-514a-3p was downregulated. OSTM1-AS1 was mostly observed in the cytoplasm, and its knockout suppressed WT cell migration and proliferation in vitro, triggered apoptosis and attenuated tumor development in vivo. MiR-514a-3p was sponged by OSTM1-AS1, and miR-514a-3p interference counteracted the tumoricidal effect of OSTM1-AS1 knockdown. MiR-514a-3p reduced WT progression by downregulating the expression of MELK, which is the target gene of miR-514a-3p. lncRNA OSTM1-AS1 acts as an oncogenic factor in WT by releasing MELK through sponging miR-514a-3p and could be a useful target for WT diagnosis and therapy. Anti-Cancer Drugs 33: 720-730
The present meta-analysis demonstrates that telomerase activity could be a useful biomarker for the differential diagnosis of pancreatic adenocarcinoma and benign pancreatic diseases.
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