scholarly journals Comprehensive analysis of PLOD family members in low-grade gliomas using bioinformatics methods

PLoS ONE ◽  
2021 ◽  
Vol 16 (1) ◽  
pp. e0246097
Author(s):  
Yonghui Zhao ◽  
Xiang Zhang ◽  
Junchao Yao
Keyword(s):  
Immune Cell ◽  
Family Members ◽  
Disease Free Survival ◽  
Low Grade ◽  
Oxidoreductase Activity ◽  
Free Survival ◽  
Expression Levels ◽  
Low Grade Gliomas ◽  
Novel Biomarkers ◽  
Lysine Degradation

Low-grade gliomas (LGGs) is a primary invasive brain tumor that grows slowly but is incurable and eventually develops into high malignant glioma. Novel biomarkers for the tumorigenesis and lifetime of LGG are critically demanded to be investigated. In this study, the expression levels of procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLODs) were analyzed by ONCOMINE, HPA and GEPIA. The GEPIA online platform was applied to evaluate the interrelation between PLODs and survival index in LGG. Furthermore, functions of PLODs and co-expression genes were inspected by the DAVID. Moreover, we used TIMER, cBioportal, GeneMINIA and NetworkAnalyst analysis to reveal the mechanism of PLODs in LGG. We found that expression levels of each PLOD family members were up-regulated in patients with LGG. Higher expression of PLODs was closely related to shorter disease-free survival (DFS) and overall survival (OS). The findings showed that LGG cases with or without alterations were significantly correlated with the OS and DFS. The mechanism of PLODs in LGG may be involved in response to hypoxia, oxidoreductase activity, Lysine degradation and immune cell infiltration. In general, this research has investigated the values of PLODs in LGG, which could serve as biomarkers for diagnosis, prognosis and potential therapeutic targets of LGG patients.

scholarly journals Comprehensive Analysis of PLOD Family Members in Low-grade Gliomas Using Bioinformatics Methods

2020 ◽  
Author(s):  
Yonghui Zhao ◽  
Xiang Zhang ◽  
Junchao Yao
Keyword(s):  
Immune Cell ◽  
Family Members ◽  
Disease Free Survival ◽  
Low Grade ◽  
Oxidoreductase Activity ◽  
Free Survival ◽  
Expression Levels ◽  
Low Grade Gliomas ◽  
Novel Biomarkers ◽  
Lysine Degradation

Abstract Low-grade gliomas (LGGs) is a primary invasive brain tumor that grows slowly but is incurable and eventually develops into high malignant glioma. Novel biomarkers for the tumorigenesis and lifetime of LGG are critically demanded to be investigated. In this study, the expression levels of procollagen-lysine, 2-oxoglutarate 5-dioxygenases (PLODs) were analyzed by ONCOMINE, HPA and GEPIA. The GEPIA online platform was applied to evaluate the interrelation between PLODs and survival index in LGG. Furthermore, functions of PLODs and co-expression genes were inspected by the DAVID. Moreover, we used TIMER, cBioportal, GeneMINIA and NetworkAnalyst analysis to reveal the mechanism of PLODs in LGG. We found that expression levels of each PLOD family members were up-regulated in patients with LGG. Higher expression of PLODs was closely related to shorter disease-free survival (DFS) and overall survival (OS). The findings showed that LGG cases with or without alterations were significantly correlated with the OS and DFS. The mechanism of PLODs in LGG may be involved in response to hypoxia, oxidoreductase activity, Lysine degradation and immune cell infiltration. In general, this research has investigated the values of PLODs in LGG, which could serve as biomarkers for diagnosis, prognosis and potential therapeutic targets of LGG patients.

scholarly journals Comprehensive Analysis of E2F Family Members in Human Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Shengbo Li ◽  
Xiaofan Yang ◽  
Wenqing Li ◽  
Zhenbing Chen
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Tumor Progression ◽  
Cell Lines ◽  
Family Members ◽  
Disease Free Survival ◽  
Mrna Levels ◽  
Free Survival ◽  
Expression Levels ◽  
Disease Free

Gastric cancer (GC) is the second most common cancer and the third most frequent cause of cancer-related deaths in China. E2Fs are a family of transcription factors reported to be involved in the tumor progression of various cancer types; however, the roles of individual E2Fs are still not known exactly in tumor progression of GC. In this study, we examined the expression of E2Fs to investigate their roles in tumor progression in GC patients using multiple databases, including ONCOMINE, GEPIA2, Kaplan-Meier plotter, cBioPortal, Metascape, LinkedOmics, GeneMANIA, STRING and UCSC Xena. We also performed real-time polymerase chain reaction (RT-PCR) to validate the expression levels of individual E2Fs in several GC cell lines. Our results demonstrated that the mRNA levels of E2F1/2/3/5/8 were significantly higher both in GC tissues and cell lines. The expression levels of E2F1 and E2F4 were correlated with poor overall survival (OS), decreased post-progression survival (PPS), and decreased progression-free survival (FP) in patients with GC. However, overexpression of E2F2, E2F5, E2F7 and E2F8 is significantly associated with disease-free survival and overall survival in patients with GC. In addition, higher E2F3 and E2F6 mRNA expression was found to increase GC patients’ OS and PPS. 224 of 415 patients with STAD (54%) had gene mutations that were associated with longer disease-free survival (DFS) but not OS. Cell cycle pathway was closely associated with mRNA level of more than half of E2Fs (E2F1/2/3/7/8). There were close and complicated interactions among E2F family members. Finally, our results indicated the gene expressions of E2Fs had a positive relationship with its copy numbers. Taken together, E2F1/2/3/5/8 can serve as biomarkers for GC patients with high prognostic value for OS of GC patients or therapeutic targets for GC.

GINS1/2/3/4 Upregulation Predicts Poor Prognosis in Human Sarcoma

2021 ◽  
Author(s):  
Gen Wu ◽  
Ziyuan Chen ◽  
Tong Wu ◽  
Jian Zhou ◽  
Qunyan Tian ◽  
...  
Keyword(s):  
Prognostic Value ◽  
Family Members ◽  
Disease Free Survival ◽  
Cancer Cell Line ◽  
Poor Overall Survival ◽  
Free Survival ◽  
Expression Levels ◽  
Kaplan Meier ◽  
Human Sarcoma ◽  
Kaplan Meier Plotter

Abstract Background: GINS family was reported to be highly expressed in many tumors. However, the association of GINS family with human sarcoma remained unknown. This study was undertaken to explore the expression and prognostic value of GINS family in human sarcoma.Methods: In terms of the expression levels of mRNA for GINS family members, a particular contrast in various cancers, especially human sarcoma, was conducted through ONCOMINE and GEPIA and CCLE databases. Kaplan-Meier Plotter was used to identify the prognostic value of GINS family in sarcoma.Results: We discovered that the mRNA expression levels of GINS1, GINS2, GINS3, and GINS4 were all higher in the majority of tumor tissues than in normal samples, of course, including sarcoma. Through the Cancer Cell Line Encyclopedia (CCLE), all the four members (GINS1, GINS2, GINS3, GINS4) expression were observed in high levels in sarcoma cell lines. In Gene Expression Profiling Analysis (GEPIA) and Kaplan-Meier Plotter, our results indicated that the poor overall survival (OS), disease-free survival (DFS) and relapse free survival (RFS) were tightly associated with the increased expression of GINS genes. Conclusion: The four GINS family members are all the prognostic biomarkers for the prognosis of human sarcoma.

scholarly journals Clinicopathological features and prognostic significance of CTNNB1 mutation in low-grade, early-stage endometrial endometrioid carcinoma

2021 ◽  
Author(s):  
Ignacio Ruz-Caracuel ◽  
Álvaro López-Janeiro ◽  
Victoria Heredia-Soto ◽  
Jorge L. Ramón-Patino ◽  
Laura Yébenes ◽  
...  
Keyword(s):  
Positive Predictive Value ◽  
Mismatch Repair ◽  
Predictive Value ◽  
Early Stage ◽  
Disease Free Survival ◽  
Low Grade ◽  
Beta Catenin ◽  
Free Survival ◽  
Disease Free ◽  
Risk Of Relapse

AbstractLow-grade and early-stage endometrioid endometrial carcinomas (EECs) have an overall good prognosis but biomarkers identifying patients at risk of relapse are still lacking. Recently, CTNNB1 exon 3 mutation has been identified as a potential risk factor of recurrence in these patients. We evaluate the prognostic value of CTNNB1 mutation in a single-centre cohort of 218 low-grade, early-stage EECs, and the correlation with beta-catenin and LEF1 immunohistochemistry as candidate surrogate markers. CTNNB1 exon 3 hotspot mutations were evaluated by Sanger sequencing. Immunohistochemical staining of mismatch repair proteins (MLH1, PMS2, MSH2, and MSH6), p53, beta-catenin, and LEF1 was performed in representative tissue microarrays. Tumours were also reviewed for mucinous and squamous differentiation, and MELF pattern. Nineteen (8.7%) tumours harboured a mutation in CTNNB1 exon 3. Nuclear beta-catenin and LEF1 were significantly associated with CTNNB1 mutation, showing nuclear beta-catenin a better specificity and positive predictive value for CTNNB1 mutation. Tumours with CTNNB1 exon 3 mutation were associated with reduced disease-free survival (p = 0.010), but no impact on overall survival was found (p = 0.807). The risk of relapse in tumours with CTNNB1 exon 3 mutation was independent of FIGO stage, tumour grade, mismatch repair protein expression, or the presence of lymphovascular space invasion. CTNNB1 exon 3 mutation has a negative impact on disease-free survival in low-grade, early-stage EECs. Nuclear beta-catenin shows a higher positive predictive value than LEF1 for CTNNB1 exon 3 mutation in these tumours. Graphical abstract

Phase I Study of Fludarabine Plus Cyclophosphamide in Patients With Previously Untreated Low-Grade Lymphoma: Results and and Long-Term Follow-Up—A Report From the Eastern Cooperative Oncology Group

2000 ◽  
Vol 18 (5) ◽  
pp. 987-987 ◽  
Author(s):  
Howard S. Hochster ◽  
Martin M. Oken ◽  
Jane N. Winter ◽  
Leo I. Gordon ◽  
Bruce G. Raphael ◽  
...  
Keyword(s):  
Phase Ii ◽  
Bone Marrow Involvement ◽  
Survival Rates ◽  
Eastern Cooperative Oncology Group ◽  
Disease Free Survival ◽  
Low Grade ◽  
Survival Times ◽  
Free Survival ◽  
Disease Free

PURPOSE: To determine the toxicity and recommended phase II doses of the combination of fludarabine plus cyclophosphamide in chemotherapy-naive patients with low-grade lymphoma. PATIENTS AND METHODS: Previously untreated patients with low-grade lymphoma were entered onto dosing cohorts of four patients each. The cyclophosphamide dose, given on day 1, was increased from 600 to 1,000 mg/m2. Fludarabine 20 mg/m2 was administered on days 1 through 5. The first eight patients were treated every 21 days; later patients were treated every 28 days. Prophylactic antibiotics were required. RESULTS: Prolonged cytopenia and pulmonary toxicity each occurred in three of eight patients treated every 3 weeks. The 19 patients treated every 28 days, who were given granulocyte colony-stimulating factor as indicated, did not have undue nonhematologic toxicity. Dose-limiting toxicity was hematologic. At the recommended phase II/III dose (cyclophosphamide 1,000 mg/m2), grade 4 neutropenia was observed in 17% of all cycles and 31% of first cycles. Grade 3 or 4 thrombocytopenia was seen in only 1% of all cycles. The median number of cycles per patient was six (range, two to 11) for all patients enrolled. The response rate was 100% of 27 patients entered; 89% achieved a complete and 11% a partial response. Nineteen of 22 patients with bone marrow involvement had clearing of the marrow. Median duration of follow-up was more than 5 years; median overall and disease-free survival times have not been reached. Kaplan-Meier estimated 5-year overall survival and disease-free survival rates were 66% and 53%, respectively. CONCLUSION: The recommended dosing for this combination in patients with previously untreated low-grade lymphoma is cyclophosphamide 1,000 mg/m2 day 1 and fludarabine 20 mg/m2 days 1 through 5. The regimen has a high level of activity, with prolonged complete remissions providing 5-year overall and disease-free survival rates as high as those reported for other therapeutic approaches in untreated patients.

scholarly journals Carboplatin and vincristine chemotherapy for children with newly diagnosed progressive low-grade gliomas

1997 ◽  
Vol 2 (3) ◽  
pp. E1
Author(s):  
Roger J. Packer ◽  
Joanne Ater ◽  
Jeffrey Allen ◽  
Peter Phillips ◽  
Russell Geyer ◽  
...  
Keyword(s):  
Objective Response ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Response To Treatment ◽  
Low Grade ◽  
Significant Prognostic Factor ◽  
Newly Diagnosed ◽  
Free Survival ◽  
Low Grade Gliomas ◽  
Response To Chemotherapy

The optimum treatment of nonresectable low-grade gliomas of childhood remains undecided. There has been increased interest in the use of chemotherapy for young children, but little information concerning the long-term efficacy of such treatment. Seventy-eight children with a mean age of 3 years (range 3 months-16 years) who had newly diagnosed, progressive low-grade gliomas were treated with combined carboplatin and vincristine chemotherapy. The patients were followed for a median of 30 months from diagnosis, with 31 patients followed for more than 3 years. Fifty-eight children had diencephalic tumors, 12 had brainstem gliomas, and three had diffuse leptomeningeal gliomas. Forty-four (56%) of 78 patients showed an objective response to treatment. Progression-free survival rates were 75 ± 6% at 2 years and 68 ± 7% at 3 years. There was no statistical difference in progression-free survival rates between children with neurofibromatosis Type 1 and those without the disease (2-year, progression-free survival 79 ± 11% vs. 75 ± 6%, respectively). The histological subtype of the tumor, its location, and its maximum response to chemotherapy did not have an impact on the duration of disease control. The only significant prognostic factor was age: children 5 years old or younger at the time of treatment had a 3-year progression-free survival rate of 74 ± 7% compared with a rate of 39 ± 21% in older children (p < 0.01). Treatment with carboplatin and vincristine is effective, especially in younger children, in controlling newly diagnosed progressive low-grade gliomas.

scholarly journals Management of low-grade glioma: a systematic review and meta-analysis

2018 ◽  
Vol 6 (4) ◽  
pp. 249-258 ◽  
Author(s):  
Timothy J Brown ◽  
Daniela A Bota ◽  
Martin J van Den Bent ◽  
Paul D Brown ◽  
Elizabeth Maher ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Progression Free Survival ◽  
Low Grade Glioma ◽  
World Health ◽  
Subtotal Resection ◽  
Low Grade ◽  
Evidence Based ◽  
Free Survival ◽  
Low Grade Gliomas

Abstract Background Optimum management of low-grade gliomas remains controversial, and widespread practice variation exists. This evidence-based meta-analysis evaluates the association of extent of resection, radiation, and chemotherapy with mortality and progression-free survival at 2, 5, and 10 years in patients with low-grade glioma. Methods A quantitative systematic review was performed. Inclusion criteria included controlled trials of newly diagnosed low-grade (World Health Organization Grades I and II) gliomas in adults. Eligible studies were identified, assigned a level of evidence for every endpoint considered, and analyzed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The relative risk of mortality and of progression at 2, 5, and 10 years was calculated for patients undergoing resection (gross total, subtotal, or biopsy), radiation, or chemotherapy. Results Gross total resection was significantly associated with decreased mortality and likelihood of progression at all time points compared to subtotal resection. Early radiation was not associated with decreased mortality; however, progression-free survival was better at 5 years compared to patients receiving delayed or no radiation. Chemotherapy was associated with decreased mortality at 5 and 10 years in the high-quality literature. Progression-free survival was better at 5 and 10 years compared to patients who did not receive chemotherapy. In patients with isocitrate dehydrogenase 1 gene (IDH1) R132H mutations receiving chemotherapy, progression-free survival was better at 2 and 5 years than in patients with IDH1 wild-type gliomas. Conclusions Results from this review, the first to quantify differences in outcome associated with surgery, radiation, and chemotherapy in patients with low-grade gliomas, can be used to inform evidence-based management and future clinical trials.

scholarly journals Validation of a clinicopathological score for the prediction of post-surgical evolution of pituitary adenoma: retrospective analysis on 566 patients from a tertiary care centre

2019 ◽  
Vol 180 (2) ◽  
pp. 127-134 ◽  
Author(s):  
S Asioli ◽  
A Righi ◽  
M Iommi ◽  
C Baldovini ◽  
F Ambrosi ◽  
...  
Keyword(s):  
Pituitary Adenomas ◽  
Proliferative Activity ◽  
Disease Free Survival ◽  
Low Grade ◽  
High Grade ◽  
Tumour Type ◽  
Disease Evolution ◽  
Free Survival ◽  
Disease Free

Objective and design A clinicopathological score has been proposed by Trouillas et al. to predict the evolution of pituitary adenomas. Aim of our study was to perform an independent external validation of this score and identify other potential predictor of post-surgical outcome. Methods The study sample included 566 patients with pituitary adenomas, specifically 253 FSH/LH-secreting, 147 GH-secreting, 85 PRL-secreting, 72 ACTH-secreting and 9 TSH-secreting tumours with at least 3-year post-surgical follow-up. Results In 437 cases, pituitary adenomas were non-invasive, with low (grade 1a: 378 cases) or high (grade 1b: 59 cases) proliferative activity. In 129 cases, tumours were invasive, with low (grade 2a: 87 cases) or high (grade 2b: 42 cases) proliferative activity. During the follow-up (mean: 5.8 years), 60 patients developed disease recurrence or progression, with a total of 130 patients with pituitary disease at last follow-up. Univariate analysis demonstrated a significantly higher risk of disease persistence and recurrence/progression in patients with PRL-, ACTH- and FSH/LH-secreting tumours as compared to those with somatotroph tumours, and in those with high proliferative activity (grade 1b and 2b) or >1 cm diameter. Multivariate analysis confirmed tumour type and grade to be independent predictors of disease-free-survival. Tumour invasion, Ki-67 and tumour type were the only independent prognostic factors of disease-free survival. Conclusions Our data confirmed the validity of Trouillas’ score, being tumour type and grade independent predictors of disease evolution. Therefore, we recommend to always consider both features, together with tumour histological subtype, in the clinical setting to early identify patients at higher risk of recurrence.

scholarly journals CDCA3 Is a Novel Prognostic Biomarker Associated with Immune Infiltration in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-19
Author(s):  
Zhihuai Wang ◽  
Shuai Chen ◽  
Gaochao Wang ◽  
Sun Li ◽  
Xihu Qin
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Immune Cell ◽  
Disease Free Survival ◽  
In Silico Analysis ◽  
Gene Markers ◽  
Free Survival ◽  
Immune Infiltration ◽  
Normal Tissues ◽  
Tumor Tissues

Cell division cycle-associated protein-3 (CDCA3) contributes to the regulation of the cell cycle. CDCA3 plays an important role in the carcinogenesis of various cancers; however, the association between CDCA3 expression, prognosis of patients, and immune infiltration in the tumor microenvironment is still unknown. Here, we demonstrated that CDCA3 was differentially expressed between the tumor tissues and corresponding normal tissues using in silico analysis in the ONCOMINE and Tumor Immune Estimation Resource (TIMER) databases. We analyzed the relationship between the expression of CDCA3 and prognosis of patients with hepatocellular carcinoma (HCC) using the Kaplan–Meier plotter database and Gene Expression Profiling Interactive Analysis (GEPIA). Furthermore, we determined the prognostic value of CDCA3 expression using univariate and multivariate analyses. We observed that CDCA3 expression closely correlated with immune infiltration and gene markers of infiltrating immune cells in the TIMER database. CDCA3 was highly expressed in the tumor tissues than in the adjacent normal tissues in various cancers, including HCC. Increased expression of CDCA3 was accompanied by poorer overall survival (OS), relapse-free survival (RFS), progression-free survival (PFS), and disease-specific survival (DSS). The correlation between CDCA3 expression and OS and disease-free survival (DFS) was also studied using GEPIA. CDCA3 expression was associated with the levels of immune cell infiltration and was positively correlated with tumor purity. Moreover, CDCA3 expression was associated with gene markers such as PD-1, CTLA4, LAG3, and TIM-3 from exhausted T cells, CD3D, CD3E, and CD2 from T cells, and TGFB1 and CCR8 located on the surface of Tregs. Thus, we demonstrated that CDCA3 may be a potential target and biomarker for the management and diagnosis of HCC.

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