Clinical significance of Polycomb gene expression in brain tumors.
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ABSTRACT:
SUBMITTER: Crea F
PROVIDER: S-EPMC2958980 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The expression and clinical significance of stomatin-like protein 2 (SLP-2) in ovarian tumors were investigated. A total of 280 cases of ovarian tissue specimens preserved from inpatients after surgical treatments in the Department of Oncology of Yidu Central Hospital of Weifang from April 2013 to May 2016 were collected, including 130 cases of malignant ovarian tumor tissue specimens (malignant tumor group), 75 cases of benign ovarian tumor tissue specimens (benign tumor group) and 75 cases of normal ovarian tissue specimens from bilateral ovariectomy for unilateral ovarian lesions (control group). Immunohistochemistry was used to detect the expression of SLP-2 protein in the three groups. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was utilized to detect the relative expression of SLP-2 mRNA in the three groups, and the relationship between SLP-2 and clinicopathological parameters of the ovarian cancer patients was analyzed. The patients with ovarian cancer were divided into the SLP-2 high-expression group and the SLP-2 low-expression group according to the median of SLP-2 relative expression. The survival of patients was analyzed using the Kaplan-Meier and Cox regression model. The results of immunohistochemistry showed that the positive expression rate of SLP-2 protein in the malignant tumor group was significantly higher than that in the benign tumor and control groups (P<0.001). The results of RT-qPCR showed that compared with the control group, the relative expression of SLP-2 mRNA in the ovarian tissues in the benign tumor group and the malignant tumor group was increased (P<0.001). The relative expression of SLP-2 mRNA in the malignant tumor group was higher than that in the benign tumor group (P<0.001). The relative expression of SLP-2 mRNA correlated with clinical stage, pathological differentiation and lymph node metastasis of the patients with ovarian cancer (P<0.05). The 5-year overall survival (OS) in the SLP-2 mRNA high expression group was significantly lower than that in the SLP-2 mRNA low expression group at 5 years (P<0.05). SLP-2 mRNA was an independent prognostic factor influencing OS of the patients (P<0.05). SLP-2 may be involved in the occurrence and development of ovarian cancer and related to the clinical stage, pathological differentiation and lymph node metastasis of the patients with ovarian cancer, which may also play a role in promoting the invasion and metastasis processes of ovarian cancer. Therefore, SLP-2 is expected to be an effective biomarker for targeted treatment and prognosis of ovarian tumor.
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Project description:Guanine nucleotide exchange factor T (GEFT), a member of the Rho guanine nucleotide exchange factor family, is expressed in a variety of tumors. In the present study, the expression and clinical significance of GEFT in malignant digestive tract tumors was assessed. Tumor and adjacent control samples from 180 patients were tested. Positive GEFT expression rates were 80, 83.33 and 86.67% in esophageal squamous carcinoma (ESCC), gastric carcinoma (GC) and colorectal cancer (CRC), respectively. GEFT expression was associated with diffuse type carcinoma according to the Lauren classification (?2=12.525, P=0.002) and tumor-node-metastasis (TNM) stages III/IV (?2=4.033, P=0.045) in GC, and with vessel carcinoma embolus (?2=7.890, P=0.005) and lymph node metastasis (?2=5.455, P=0.020) in CRC, but was not associated with other clinicopathological parameters. Patients with high levels of GEFT protein expression had a less favorable outcome compared with patients with low levels of GEFT expression in patients with CRC (?2=3.876, P=0.049). However, a significant association was not found between GEFT expression and overall survival in patients with ESCC (?2=0.040, P=0.842) or GC (?2=0.501, P=0.479). The rate of human epidermal growth factor receptor 2 upregulation in patients with GC was 13.33% and it was associated with nerve invasion (?2=4.005, P=0.045) and TNM stages III/IV (?2=5.600, P=0.018). Mismatch repair protein (MMRP) defect was observed in six cases, and the KRAS mutation rate was 26.67% in patients with CRC. GEFT expression was significantly correlated with MMRP (r=-0.285, P=0.027) and KRAS mutation in patients with CRC (r=0.697, P<0.001). These findings revealed frequent GEFT upregulation in malignant digestive tract tumors, which may have promoted tumor development. GEFT expression in CRC may be associated with microsatellite instability and KRAS mutation status, suggesting that GEFT may be a potential therapeutic target for patients with CRC.
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Project description:Primary outcome(s): The clinical significance of immune and gene-expression profile in colorectal cancer
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Project description:Abstract: CRNDE is an oncogene expressed as a long non-coding RNA. However, our team previously reported that the CRNDE gene also encodes a micropeptide, CRNDEP. The amino acid sequence of CRNDEP has recently been revealed by other researchers, too. This study aimed to investigate genetic alterations within the CRNDEP-coding region of the CRNDE gene, methylation profiling of this gene, and CRNDEP expression analysis. All investigations were performed on clinical material from patients with ovarian tumors of diverse aggressiveness. We found that CRNDEP levels were significantly elevated in highly aggressive tumors compared to benign neoplasms. Consistently, a high level of this micropeptide was a negative, independent, prognostic, and predictive factor in high-grade ovarian cancer (hgOvCa) patients. The cancer-promoting role of CRNDE(P), shown in our recent study, was also supported by genetic and epigenetic results obtained herein, revealing no CRNDEP-disrupting mutations in any clinical sample. Moreover, in borderline ovarian tumors (BOTS), but not in ovarian cancers, the presence of a single nucleotide polymorphism in CRNDE, rs115515594, significantly increased the risk of recurrence. Consistently, in BOTS only, the same genetic variant was highly overrepresented compared to healthy individuals. We also discovered that hypomethylation of CRNDE is associated with increased aggressiveness of ovarian tumors. Accordingly, hypomethylation of this gene’s promoter/first exon correlated with hgOvCa resistance to chemotherapy, but only in specimens with accumulation of the TP53 tumor suppressor protein. Taken together, these results contribute to a better understanding of the role of CRNDE(P) in tumorigenesis and potentially may lead to improvements in screening, diagnosis, and treatment of ovarian neoplasms.
2024-07-27 | GSE262765 | GEO
Project description:Cancer-germline genes (CGGs) code for immunogenic antigens that are present in various human tumors and can be targeted by immunotherapy. Their expression has been studied in a wide range of human tumors in adults. We measured the expression of 12 CGGs in pediatric brain tumors, to identify targets for therapeutic cancer vaccines. Real Time PCR was used to quantify the expression of genes MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MAGE-C2, NY-ESO-1 and GAGE-1,2,8 in 50 pediatric brain tumors of different histological subtypes. Protein expression was examined with immunohistochemistry. Fifty-five percent of the medulloblastomas (n = 11), 86% of the ependymomas (n = 7), 40% of the choroid plexus tumors (n = 5) and 67% of astrocytic tumors (n = 27) expressed one or more CGGs. Immunohistochemical analysis confirmed qPCR results. With exception of a minority of tumors, the overall level of CGG expression in pediatric brain tumors was low. We observed a high expression of at least one CGG in 32% of the samples. CGG-encoded antigens are therefore suitable targets in a very selected group of pediatric patients with a brain tumor. Interestingly, glioblastomas from adult patients expressed CGGs more often and at significantly higher levels compared to pediatric glioblastomas. This observation is in line with the notion that pediatric and adult glioblastomas develop along different genetic pathways.
| S-EPMC2440921 | biostudies-literature
Project description:Glioblastoma (GBM) represents the most common and aggressive malignant primary brain tumors in adults. Response to standard treatment is transitory and the survival of clinical trial cohorts are little more than 14 months. GBM are characterized by excessive proliferation, invasiveness, and radio-/chemoresistance features; which are strongly upregulated by transforming growth factor-beta (TGF-?). We hypothesized that TGF-? gene expression could correlate with overall survival (OS) and serve as a prognostic biomarker. TGF-?? and -?? expression were analyzed by qPCR in 159 GBM tumor specimens. Kaplan-Meier and multivariate analyses were used to correlate expression with OS and progression-free survival (PFS). In GBM, TGF-?? and -?? levels were 33- and 11-fold higher respectively than in non-tumoral samples. Kaplan-Meier and multivariate analyses revealed that high to moderate expressions of TGF-?? significantly conferred a strikingly poorer OS and PFS in newly diagnosed patients. Interestingly, at relapse, neither isoforms had meaningful impact on clinical evolution. We demonstrate that TGF-?? is the dominant isoform in newly diagnosed GBM rather than the previously acknowledged TGF-??. We believe our study is the first to unveil a significant relationship between TGF-?? expression and OS or PFS in newly diagnosed GBM. TGF-?? could serve as a prognostic biomarker or target affecting treatment planning and patient follow-up.
| S-EPMC5979513 | biostudies-literature
Project description:BackgroundHigh-grade gliomas (HGGs) exhibit marked heterogeneity in clinical behavior. The purpose of this study was to identify a novel biomarker that predicts patient outcome, which is helpful in HGG patient management.MethodsWe analyzed gene expression profiles of 833 HGG cases, representing the largest patient population ever reported. Using the data set from the Cancer Genome Atlas (TCGA) and random partitioning approach, we performed Cox proportional hazards model analysis to identify novel prognostic mRNAs in HGG. The predictive capability was further assessed via multivariate analysis and validated in 4 additional data sets. The Kaplan-Meier method was used to evaluate survival difference between dichotomic groups of patients. Correlation of gene expression and DNA methylation was evaluated via Student's t-test.ResultsPatients with elevated FBXO17 expression had a significantly shorter overall survival (OS) (P?=?0.0011). After adjustment by IDH1 mutation, sex, and patient age, FBXO17 gene expression was significantly associated with OS (HR?=?1.29, 95% CI =1.04-1.59, P?=?0.018). In addition, FBXO17 expression can significantly distinguish patients by OS not only among patients who received temozolomide chemotherapy (HR 1.35, 95% CI =1.12-1.64, P?=?0.002) but also among those who did not (HR?=?1.48, 95% CI =1.20-1.82, P?<?0.0001). The significant association of FBXO17 gene expression with OS was further validated in four external data sets. We further found that FBXO17 endogenous expression is significantly contributable from its promoter methylation.ConclusionEpigenetically modulated FBXO17 has a potential as a stratification factor for clinical decision-making in HGG.
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Project description:BACKGROUND:Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Surgical resection and tyrosine kinase inhibitors are defined as the main treatments but cannot cure patients with advanced GIST, which eventually develops into recurrence and acquired drug resistance. Therefore, it is necessary to identify prognostic biomarkers and new therapeutic targets for GISTs. CC chemokine receptor type 8 (CCR8) protein participates in regulation of immune responses. Recent studies on CCR8 in non-small cell lung cancer and colorectal cancer showed that it was highly expressed in tumor-infiltrating regulatory T cells and correlated with a poor prognosis. AIM:To detect CCR8 expression in GIST tissues and analyze its relationships with clinicopathological features and prognosis in patients with GISTs. METHODS:Tissue samples were used for the tissue microarrays construction. The microarrays were then subjected to immunohistochemical analyses to detect CCR8 expression. Next, Kaplan-Meier analysis was utilized to calculate the survival rate of patients with complete follow-up data, and the potential prognostic value of CCR8 was evaluated by Cox regression analysis. Finally, a Gene Ontology/Kyoto Encyclopedia of Genes and Genomes single-gene enrichment chart of CCR8 was constructed using the STRING database. RESULTS:CCR8-positive signals were detected as brown or brown-yellow particles by immunohistochemistry located in the cytoplasm. Among 125 tissue samples, 74 had CCR8 high expression and 51 had low or negative expression. Statistical analyses suggested CCR8 was significantly correlated with tumor size, mitotic index, AFIP-Miettinen risk classification and tumor location. Kaplan-Meier and multivariate analyses showed that patients with low or negative CCR8 expression, mitotic index < 5/high-power fields (HPF) and tumor diameter < 5 cm had a better prognosis. Based on the STRING database, CCR8 was significantly enriched in biological processes such as tumor immunity, T lymphocyte chemotaxis, migration and pathways like the nuclear factor-?B and tumor necrosis factor pathways as well as intestinal immune regulation networks. CONCLUSION:CCR8 is a prognostic biomarker for malignant potential of GISTs, with high expression correlated with malignancy and poor prognosis.
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Project description:The aim of the study was to investigate the expression and clinical significance of early growth response protein 1 (EGR-1) and phosphatase and tensin homolog (PTEN) in the pituitary tumors of elderly patients. From January 2014 to December 2015, we collected 25 patient cases with non-invasive pituitary tumors, 10 cases with invasive pituitary tumors and 35 cases with healthy pituitary tissues (the healthy control group). Immunohistochemical staining was used to detect the expression of EGR-1 and PTEN, and analyze specific differences. The expression of EGR-1 and PTEN in patients with invasive and non-invasive pituitary tumors increased significantly, when compared with the healthy control group, and the difference was statistically significant (p<0.05). In patients with invasive tumors, EGR-1 levels were higher than levels in patients with non-invasive tumors. The difference was statistically significant (p<0.05). PTEN levels in patients with invasive tumors were significantly lower than levels in patients with non-invasive tumors. The difference was statistically significant (p<0.05). In conclusion, EGR-1 and PTEN levels in patients with pituitary tumors were significantly higher. In addition, EGR-1 levels were higher in patients with invasive pituitary tumors, while PTEN levels were lower. The combination of increases in both levels highlights an important role in the evaluation and prognosis of elderly patients with pituitary tumors.
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Project description:Claudins are integral to the structure and function of tight junctions. Altered claudin expression has been shown to affect disease behavior and patient prognosis in various neoplasms. The objectives of this study were to analyze the claudin-1, -4 and -7 expression in odontogenic tumors and characterize their expression pattern in distinct tumor cell types in relation to the recurrence potential. Sixty-nine cases of odontogenic tumors, including 43 ameloblastomas (AM), 17 adenomatoid odontogenic tumors (AOT), 6 ameloblastic fibromas (AF) and 3 ameloblastic carcinomas (AC) were investigated for claudin-1, -4 and -7 expression immunohistochemically. The staining was analyzed semi-quantitatively and categorized into 4 levels, based on the percentage of positively stained neoplastic epithelial cells. Claudin-1 was expressed in all AOT and AF cases, whereas most AC (66.7%) showed no expression. The claudin-1 staining was moderate-to-intense in the odontogenic epithelium of AF. In contrast, its staining of ameloblast-like cells and stellate reticulum-like cells in AM was weak. Claudin-7 expression was noted in all tumor types studied, while the expression of claudin-4 was limited and mainly localized in the squamous differentiated cells of AM and AC. AM showed significantly higher claudin-4, but lower claudin-7 expression than AOT. In addition, AC showed diminished claudin-1 immunoreactivity, compared to AOT. Low claudin-1 expression in AM was significantly associated with the increased clinical recurrence. The loss of claudin-1 may underlie the locally invasive nature of AM.
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