Overexpression of SKA Complex Is Associated With Poor Prognosis in Gliomas.
Ontology highlight
ABSTRACT:
SUBMITTER: Yu S
PROVIDER: S-EPMC8791909 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:High-grade gliomas are the most threatening brain tumors due to aggressive proliferation and poor prognosis. Thus, utilizing genetic glioma biomarkers to forecast prognosis and guide clinical management is crucial. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 3 (PLOD3) modulates cancer progression and metastasis. However, its detailed function in cancer remains largely uninvestigated. PLOD3 expression was evaluated with real-time PCR in glioblastoma (GBM) cell lines and by Gene Expression Omnibus dataset analysis and immunohistochemistry of glioma tissues. We investigated the clinical use of PLOD3 for determining glioma prognosis. The biological roles of PLOD3 in proliferation, migration and invasion of GBM cells were studied both in vitro with wound-healing and transwell assays and in vivo using an orthotopic xenograft mouse model. Hypoxia and western blotting were applied to discover the molecular mechanisms underlying PLOD3 functions. PLOD3 mRNA and protein expression were upregulated in glioma tissues compared to normal brain tissues. PLOD3 overexpression was correlated with negative survival in glioma patients. PLOD3 silencing suppressed cell proliferation and induced G1 phase arrest through p53-independent regulation of the p21 pathway. Inhibition of PLOD3 in glioma cells decreased VEGF expression, migration and invasion by downregulating mesenchymal markers, including Snail and Twist. Notably, knockdown of PLOD3 inhibited HIF-1? accumulation via the ERK signaling pathway under hypoxia. Taken together, these discoveries reveal that PLOD3 is a potential therapeutic target in human gliomas.
| S-EPMC5884658 | biostudies-literature
Project description:CMTM6, a previously uncharacterized protein, was identified as a critical regulator of PD-L1, which is reported as an immune checkpoint inhibitor, to modulate the T cell activities both in vitro and in vivo of other tumors. However, the role of CMTM6 has so far remained unclear in glioma. To investigate the role of CMTM6 in gliomas, we analyzed the transcriptome level, genomic profiles and its relationship with clinical practice. 1862 glioma samples with transcriptome data were enrolled in this study, including CGGA RNA-seq, TCGA RNA-seq, CGGA-microarray, GSE16011 and IVY GBM databases. Clinical information and genomic profiles containing somatic mutations and DNA copy numbers were also obtained. We found that CMTM6 expression was highly correlated with major clinical and molecular characteristics. Cases with high CMTM6 expression were more likely to be predicted as malignant entities and frequent with genomic aberrations of driver oncogenes. Moreover, gene ontology analysis based on significantly correlated genes of CMTM6 expression exhibited that CMTM6 was associated with immune responses and inflammatory activities. CMTM6 was synthetic with other immune checkpoint inhibitors. Additionally, CMTM6 was involved in immune functions via modulating T-lymphocyte-mediated anti-tumor immunity. Finally, high CMTM6 expression was associated with reduced survival time and may serve as a strong indicator of poor prognosis in gliomas. In brief, High level of CMTM6 expression is closely related to high malignant gliomas. Meanwhile, CMTM6 plays an important role in regulating T cell activation and antitumor responses. Therefore, CMTM6 is a promising target for developing immunotherapy of gliomas.
| S-EPMC6156716 | biostudies-literature
Project description:Mitochondrial serine hydroxyl-methyltransferase 2 (SHMT2), participating in the synthesis of mitochondrial thymidine monophosphate, has been reported to drive glioma cell survival in ischemia. However, its clinical relevance in gliomas remains unclear. In the current study, immunohistochemistry was performed to examine subcellular localization and expression levels of SHMT2 protein in glioma and non-neoplastic brain tissue specimens. Then, the associations of SHMT2 expression with various clinicopathological features and patients' prognosis were statistically evaluated. The roles of SHMT2 in the proliferation and invasion of glioma cells after siRNA-SHMT2 vector transfection were also detected by cell counting kit-8 and transwell assays, respectively. Results showed that SHMT2 immunostaining was predominantly localized in the cellular cytoplasm of tumor cells in glioma tissues but weakly in non-neoplastic brain tissues. Statistically, SHMT2 protein expression was significantly higher in glioma tissues than in non-neoplastic brain tissues (P<0.001). In addition, SHMT2 overexpression more frequently occurred in glioma patients with an advanced grade of malignancy (P<0.001) and poor prognosis (P=0.001). Notably, multivariate analysis based on a Cox regression model identified SHMT2 expression as an independent prognostic factor for glioma patients (P=0.01). Functionally, SHMT2 knockdown efficiently suppressed the proliferation (P=0.02) and invasion (P<0.001) of glioma cells in vitro. In conclusion, our findings suggest that SHMT2 may function as an oncogene in glioma development and progression. Clinically, SHMT2 may serve as a prognostic factor and as a potential therapeutic target for human gliomas.
| S-EPMC5538688 | biostudies-other
Project description:The role of SLC3A2, a gene implicated in disulfidptosis, has not been characterized in gliomas. This study aims to clarify the prognostic value of SLC3A2 and its influence on glioma. We evaluated the expression of SLC3A2 and its prognostic importance in gliomas using publicly accessible databases and our clinical glioma samples and with reliance on Meta and Cox regression analysis approaches. Functional enrichment analyses were performed to explore SLC3A2's function. Immune infiltration was evaluated using CIBERSORT, ssGSEA, and single-cell sequencing data. Additionally, Tumor immune dysfunction and exclusion (TIDE) and epithelial-mesenchymal transition scores were determined. CCK8, colony formation, migration, and invasion assays were utilized in vitro, and an orthotopic glioma xenograft model was employed in vivo, to investigate the role of SLC3A2 in gliomas. Bioinformatics analyses indicated high SLC3A2 expression correlates with adverse clinicopathological features and poor patient prognosis. Upregulated SLC3A2 influenced the tumor microenvironment by altering immune cell infiltration, particularly of macrophages, and tumor migration and invasion. SLC3A2 expression positively correlated with immune therapy indicators, including immune checkpoints and TIDE. Elevated SLC3A2 was revealed as an independent risk element for poor glioma prognosis through Cox regression analyses. In vitro experiments showed that reduced SLC3A2 expression decreased cell proliferation, migration, and invasion. In vivo, knockdown of SLC3A2 led to a reduction in tumor volume and prolonged survival in tumor-bearing mice. Therefore, SLC3A2 is a prognostic biomarker and associated with immune infiltration in gliomas.
| S-EPMC11231275 | biostudies-literature
Project description:BACKGROUND:SKA1, an important mitosis protein, has been indicated in the initiation and progression of several malignancies. However, its clinical significance in hepatocellular carcinoma (HCC) remain to be elucidated. METHODS:mRNA expression of SKA1 was examined in 126 HCC and paired non-neoplastic tissues using real-time PCR and validated in The Cancer Genome Atlas (TCGA) database. SKA1 protein expression was detected using immunohistochemistry in the 126 HCC tissues and its associations with clinicopathological parameters and prognosis were analyzed. Hierarchical cluster analysis and gene set enrichment analysis (GSEA) were performed in selected Gene Expression Omnibus data sets. RESULTS:SKA1 mRNA expression was significantly elevated in HCC tissues from both local hospital and TCGA database. Immunohistochemistry revealed that increased SKA1 expression was present in 65 of the 126 cases and was significantly associated with higher serum alpha-fetoprotein concentration, larger tumor size and higher TNM stage. Patients with positive SKA1 expression showed significantly worse overall and relapse-free survival. Multivariate Cox regression analysis revealed that SKA1 was an independent predictor of patient prognosis. Gene expression profiling analysis of public data showed that high-SKA1 expression HCC tissues had similar gene expression profiles with fetal liver tissues. Moreover, GSEA showed that genes up-regulated in high SKA1 HCC subgroup were significantly enriched in cell cycle pathway, while genes down-regulated were significantly enriched in apoptosis pathway. CONCLUSIONS:Our findings indicate that the oncofetal gene SKA1 might be involved in the progression of the HCC and could serve as a prognostic marker for HCC.
| S-EPMC6288885 | biostudies-literature
Project description:Peroxiredoxin IV (PRDX4) is a multifunctional protein that is involved in cell protection against oxidative injury, regulation of cell proliferation, modulation of intracellular signaling, and the pathogenesis of tumors. We previously conducted a proteomic analysis to investigate tumor-specific protein expression in gastric cancer. The aim of the present study was to investigate whether PRDX4 could be a marker of poor prognosis in patients with gastric cancer. Immunohistochemistry was used to validate PRDX4 as a prognostic marker for gastric cancer. Short hairpin RNA (shRNA)-mediated knockdown of PRDX4 expression in AGS cells and MKN28 cells was used for functional studies, and PRDX4 overexpression in PRDX4-depleted cells was used for knock-in studies. Based on immunohistochemistry data, TNM stage and PRDX4 were independent prognostic factors in the Cox proportional hazard model (P<0.05). In the survival analysis, the PRDX4-overexpressing group demonstrated significantly worse survival than the PRDX4-underexpression group (P<0.01). In vitro, knockdown of PRDX4 expression by shRNA caused a significant decrease in cancer invasion. Conversely, overexpression of PRDX4 in PRDX4-depleted cancer cells promoted migration and invasion. By measuring the expression of EMT-related genes, we found that E-cadherin was increased in shPRDX4 cells compared with control shMKN28 cells, and snail and slug were decreased in shPRDX4-1 cells compared with sh-control cells. Furthermore, the expression levels of these genes could be recovered in rescue experiments. In conclusion, the results of the present study suggested that PRDX4 is a marker of poor prognosis in gastric cancer and that PRDX4 is associated with cancer cell migration and invasion via EMT.
| S-EPMC7114939 | biostudies-literature
Project description:Esophageal squamous cell carcinoma (SCC) is frequently diagnosed at advanced stage and associated with poor prognosis. This study aimed to identify differentially expressed genes for further evaluated as biomarkers for predicting survival of the patients. Five paired of cancerous and normal tissues from esophageal SCC patients were subjected to cDNA microarray analysis and one of these differentially expressed genes, NEK6, was further verified in esophageal SCC tissues. The data showed 444 up-regulated genes and 918 down-regulated genes in tumor tissues (2 folds as a cut-off value). qRT-PCR data showed that 20 of 30 (66.7%) increased levels of NEK6 mRNA in cancerous tissues compared to that of distant normal tissues, while immunohistochemical data showed that 49/94 (52.13%) of the archived esophageal SCC tissues expressed higher levels of NEK6 than that of normal tissues. NEK6 expression was associated with depth of tumor invasion (P=0.005), lymph node metastasis (P=0.018), and advanced clinical tumor stages (P=0.004) of these 94 patients. Kaplan Meier curve showed that the overall survival of NEK6-positive patients was much lower than those of NEK6-negative patients (P<0.001). The median survival of NEK6-positive patients was 23 months, whereas the median survival of NEK6-negative patients was 64 months. The cumulative 5-year survival rate of NEK6-positive patients was 14.3% (7/49), whereas the rate of NEK6-negative patients was 64.4% (29/45). Multivariate analysis showed that N classification (P=0.002) and NEK6 expression (P<0.001) were independent predictors for esophageal SCC patients. These data demonstrated that NEK6 expression may serve as an independent prognostic indicator for patients with esophageal SCC. Gene expression in five paired of cancerous and normal tissues from esophageal SCC patients were measured using Human Genome 4x44K v2 Microarray.
2013-09-30 | E-GEOD-45168 | biostudies-arrayexpress
Project description:Foxj2, a novel member of Forkhead box family, has been reported to play an important role in tumorigenesis, progression, and metastasis of certain cancers. However, the expression status and effects of Foxj2 on nasopharyngeal carcinoma (NPC) progression and metastasis remain debated. In this study, we first examined the expression of Foxj2 in NPC by immunohistochemistry and Western blotting analysis. We confirmed significantly elevated expression of Foxj2 in NPC tissues and cell lines. Next, the relationships between Foxj2 expression levels and the clinicopathological factors were investigated. Its expression level correlated with T-classification (P=0.026), distant metastasis (P=0.004), and clinical stage (P=0.029). In addition, high expression of Foxj2 was associated with poor prognosis in NPC patients. The effects of Foxj2 on cell proliferation and migration were explored by RNA interference (RNAi) with CCK-8 assay, cell cycle analyses, wound healing, and transwell assay. In conclusion, our data indicate that Foxj2 upregulation promotes the progression and migration of NPC. It makes Foxj2 serve as a potential therapeutic target for the treatment of NPC.
| S-EPMC5533490 | biostudies-other
Project description:ObjectiveKallikrein 5 (KLK5), which is frequently observed in normal cervico-vaginal fluid, is known to be related to prognosis in several solid tumors. We investigated the prognostic significance of KLK5 in uterine cervical cancer using tumor tissue microarray and immunohistochemistry staining.MethodsWe analyzed samples of 165 patients with uterine cervical cancer who received definitive radiation therapy between 2004 and 2012. We divided patients into two groups stratified by their KLK5 activity by immunohistochemistry staining: negative/weak (0-1+) (n=120 patients) and moderate/strong (2-3+) group (n=45 patients). Patient and tumor characteristics, patterns of failure, and survival outcomes were compared. Univariable and multivariable analyses were performed to identify prognostic factors.ResultsPatients with KLK5 2-3+ were younger (median: 52 vs. 60 years) and had frequent paraaortic lymph node involvement (40.0% vs. 18.3%) than those with KLK5 0-1+. With a median follow-up of 60.8 (interquartile range, 47.5-77.9) months, patients with KLK5 2-3+ had inferior 5-year locoregional recurrence-free survival and distant metastasis-free survival of 61.7% (vs. 77.5% in KLK5 0-1+ group) and 59.4% (vs. 72.8% in the KLK5 0-1+ group), respectively (all p<0.05). KLK5 2-3+ expression retained its significance after adjusting for other well-known prognostic factors of tumor size and stage in multivariable analysis.ConclusionsKLK5 overexpression is associated with the aggressiveness of cervical cancer and may underlie the diminished response to conventional treatments. Therefore, KLK5 could be a reliable prognostic factor in cervical cancer.
| S-EPMC7593226 | biostudies-literature
Project description:Background & aimsHepatocellular carcinoma (HCC) has high potential for recurrence, even in curative operative cases. Although several molecular-targeting drugs have been applied to recurrent HCC, their effectiveness has been limited. This study therefore aims to develop novel cancer drugs through protein methylation.MethodsWe investigated the role of KDM5B/JARID1B, a member of JmjC histone demethylase, in HCC. Expression profiles of KDM5B were examined by immunohistochemical analysis in 105 HCC clinical tissue samples. To examine functional effects of KDM5B using HCC cell lines, we performed loss-of-function analysis treated with KDM5B-specific small interfering RNAs (siKDM5B).ResultsAll HCC cases were divided into KDM5B-positive expression group (n=54) and negative expression group (n=51). In five-year overall survival, KDM5B-positive group had poorer prognosis than KDM5B-negative (61% vs 77%, p=0.047). KDM5B-positive group had much poorer prognosis than that of the negative group, especially in HCC derived from persistent infection of hepatitis B virus (HBV) or hepatitis C virus (HCV) (54% vs 78%, p=0.015). Multivariate analysis indicated that KDM5B was the strongest risk factor for poor prognosis, especially in HCC derived from HBV/HCV. Inhibition of KDM5B could significantly suppress HCC cell proliferation through no promotion from G1 to S phase. Real-time PCR and Western blotting demonstrated that E2F1/E2F2 were downstream genes of KDM5B.ConclusionsOverexpression of KDM5B results in poor prognosis in HCC that especially derived from HBV/HCV. KDM5B appears to be an ideal target for the development of anti-cancer drugs.
| S-EPMC6188148 | biostudies-literature