scholarly journals Elevated Expression of Gamma-Glutamyl Hydrolase Is Associated With Poor Prognosis and Altered Immune Signature in Uterine Corpus Endometrial Carcinoma

2022 ◽  
Vol 12 ◽  
Author(s):  
Cong Yu ◽  
Haining Qi ◽  
Yanhui Zhang ◽  
Wen Zhao ◽  
Guoying Wu
Keyword(s):  
Endometrial Carcinoma ◽  
Poor Prognosis ◽  
Univariate Analysis ◽  
Clinicopathological Features ◽  
Gene Set Enrichment Analysis ◽  
Expression Level ◽  
Survival Prediction ◽  
Uterine Corpus ◽  
Gamma Glutamyl ◽  
Pathway Gene

Uterine corpus endometrial carcinoma (UCEC) is a common malignant tumor of the female reproductive system with poor prognosis in advanced, recurrent, and metastatic cases. Identification of reliable molecular markers will help in the development of clinical strategies for early detection, diagnosis, and intervention. Gamma-glutamyl hydrolase (GGH) is a key enzyme in folate metabolism pathway. High expression of GGH is associated with severe clinicopathological features and poor prognosis of several cancers. High GGH expression is also related to cell resistance to antifolate drugs such as methotrexate. In this study we focused on the prognostic value of immunohistochemical GGH expression level in UCEC tissue and RNA-seq data from The Cancer Genome Atlas to establish associations with clinical features and outcomes. Further, we conducted comprehensive bioinformatics analyses to identify and functionally annotate differentially expressed genes (DEGs) associated with UCEC upregulation and assessed the effects of upregulation on immune infiltration. Both GGH mRNA and protein expression levels were elevated in tumor tissues, and higher expression was significantly associated with advanced clinicopathological features and poor prognosis by univariate analysis. Further multivariate analysis identified elevated GGH expression as an independent risk factor for poor outcome. Nomograms including GGH expression yielded a c-index for disease-specific survival prediction of 0.884 (95% confidence interval: 0.861–0.907). A total of 520 DEGs (111 upregulated and 409 downregulated) were identified between high and low GGH expression groups. Analysis using Gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway, Gene set enrichment analysis, and protein‒protein interaction indicated significant associations of altered GGH expression with cell proliferation, immune response, and the occurrence and development of UCEC tumors. Finally, GGH expression level was associated with high Th2 cell and low natural killer CD56bright cell infiltration. Collectively, these findings indicate that GGH drives UCEC progression and could be a useful biomarker for survival prediction as well as a therapeutic target.

scholarly journals Down-regulation of miRNA-30c predicts poor prognosis in Colorectal Cancer patients

2016 ◽  
Vol 24 (4) ◽  
pp. 369-375
Author(s):  
Liu Bin ◽  
Meng Zhang ◽  
Liu Lixia ◽  
Zang Aimin ◽  
Yang Hua ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Poor Prognosis ◽  
Univariate Analysis ◽  
Clinicopathological Features ◽  
Expression Level ◽  
Rt Pcr ◽  
Normal Tissues ◽  
Node Metastasis ◽  
Treatment Measures ◽  
Colorectal Cancer Patients

Abstract Background: MiRNA-30c was a tumor suppressor in several human cancers, however, its association with clinicopathological features and prognosis in colorectal cancer (CRC) is unclear. Materials and Methods: The expression level of miRNA-30c in 192 pairs of colorectal cancer and adjacent normal tissues was detected by Quantitative RT-PCR, the association between miRNA-30c expression and clinical characteristics and prognosis were statistically analyzed. Results: miRNA-30c was significantly lower in CRC tissues specimens compared with matched normal adjacent tissue (P<0.001). MiRNA-30c was positively correlated with tumor size (P=0.012), TMN stage (P=0.002) and lymph node metastasis (P=0.004). The univariate analysis showed CRC patients with low miRNA-30c had distinctly shorter overall survival (P<0.001) than patients with high miRNA-30c expression level. The multivariate analysis was performed and informed that low miRNA-30c expression (P<0.001) might be an independent prognostic predictor for poor prognosis. Conclusion: miRNA-30c could predict the prognosis of colorectal cancer which is helpful to choose reasonable treatment measures.

scholarly journals Expression of LOX Suggests Poor Prognosis in Gastric Cancer

2021 ◽  
Vol 8 ◽  
Author(s):  
Jinfeng Zhu ◽  
Chen Luo ◽  
Jiefeng Zhao ◽  
Xiaojian Zhu ◽  
Kang Lin ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Logistic Regression ◽  
Regression Analysis ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Gene Set Enrichment Analysis ◽  
High Expression ◽  
Expression Level ◽  
Cox Regression Analysis

Background: Lysyl oxidase (LOX) is a key enzyme for the cross-linking of collagen and elastin in the extracellular matrix. This study evaluated the prognostic role of LOX in gastric cancer (GC) by analyzing the data of The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) dataset.Methods: The Wilcoxon rank-sum test was used to calculate the expression difference of LOX gene in gastric cancer and normal tissues. Western blot and immunohistochemical staining were used to evaluate the expression level of LOX protein in gastric cancer. Kaplan-Meier analysis was used to calculate the survival difference between the high expression group and the low expression group in gastric cancer. The relationship between statistical clinicopathological characteristics and LOX gene expression was analyzed by Wilcoxon or Kruskal-Wallis test and logistic regression. Univariate and multivariate Cox regression analysis was used to find independent risk factors affecting the prognosis of GC patients. Gene set enrichment analysis (GSEA) was used to screen the possible mechanisms of LOX and GC. The CIBERSORT calculation method was used to evaluate the distribution of tumor-infiltrating immune cell (TIC) abundance.Results: LOX is highly expressed in gastric cancer tissues and is significantly related to poor overall survival. Wilcoxon or Kruskal-Wallis test and Logistic regression analysis showed, LOX overexpression is significantly correlated with T-stage progression in gastric cancer. Multivariate Cox regression analysis on TCGA and GEO data found that LOX (all p &lt; 0.05) is an independent factor for poor GC prognosis. GSEA showed that high LOX expression is related to ECM receptor interaction, cancer, Hedgehog, TGF-beta, JAK-STAT, MAPK, Wnt, and mTOR signaling pathways. The expression level of LOX affects the immune activity of the tumor microenvironment in gastric cancer.Conclusion: High expression of LOX is a potential molecular indicator for poor prognosis of gastric cancer.

scholarly journals RNF208 is a Biomarker Associated with Immune Infiltration in Low-Grade Gliomas

2021 ◽  
Author(s):  
tong cheng ◽  
Manyu Xu ◽  
Bowen Wu ◽  
Sutian Jiang ◽  
Qianqian Wu ◽  
...  
Keyword(s):  
Cox Regression ◽  
Univariate Analysis ◽  
Gene Set Enrichment Analysis ◽  
Expression Level ◽  
Low Grade ◽  
Who Grade ◽  
Expression Levels ◽  
Immune Infiltration ◽  
Low Grade Gliomas ◽  
Infiltrating Cells

Abstract Background: Gliomas that contain common tumors originating in the central nervous system include low-grade gliomas (LGGs) and high-grade gliomas (HGGs). RNF208 is a gene that has not been researched in LGGs. Methods: Our study appraised the function of RNF208 in LGGs using data from The Cancer Genome Atlas (TCGA) database. The RNF208 expression level was analyzed via the Oncomine and TCGA database. The association between RNF208 expression levels and the clinical survival outcomes was evaluated by using COX regression and Kaplan-Meier plotting analysis. CIBERSORT was applied to investigate the correlation between RNF208 expression levels and cancer immune infiltrating cells. To explore relevant biological processes, we carried out Gene Set Enrichment Analysis. A protein network interacting with RNF208 was also established using the STRING tool. Results: A group of data of LGGs patients based on the TCGA database revealed that high RNF208 expression level was relevant to a favorable prognosis. Besides, RNF208 expression that served as an independent factor was significantly correlated with WHO grade groups in univariate analysis. Furthermore, RNF208 expression was negatively correlated with the immune infiltration level of 22 species of immune infiltrating cells and immune checkpoints including PD1, PDL2, TIM3, and CTLA4. GSEA showed that 20 biological pathways were discriminatively enriched in the RNF208 low expression level. Conclusions: Our findings revealed that RNF208 would be regarded as a promising prognostic biomarker in LGGs.

scholarly journals P14.122 Integrin α5 is a poor prognostic factor in patients with glioblastoma treated by the Stupp protocol

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii97-iii97
Author(s):  
N Etienne-Selloum ◽  
J Prades ◽  
D Bello Roufai ◽  
F El Azumi ◽  
M Boone ◽  
...  
Keyword(s):  
Protein Expression ◽  
Survival Data ◽  
Poor Prognosis ◽  
Univariate Analysis ◽  
Expression Level ◽  
Rank Test ◽  
Protein Expression Level ◽  
Poor Prognostic Factor ◽  
Integrin Α5 ◽  
Stupp Protocol

Abstract BACKGROUND Integrin α5β1 was suggested to be involved in glioblastoma (GBM) aggressiveness through preclinical studies and genomic analysis of several cohorts of patients. However, protein expression data are still missing to confirm this hypothesis. Our aim was to investigate the prognostic value of integrin α5 protein expression level in GBM. MATERIAL AND METHODS We retrospectively determined the protein expression level of integrin α5 using immunochemistry in tumors from patients treated in 6 French centers. Paraffin sections of GBM were labeled by immunofluorescence and analyzed by confocal microscopy. The corresponding clinical and survival data have been identified and analyzed. The primary end-point was overall survival (OS). RESULTS Out of 297 patients newly diagnosed with GBM between 2006 and 2013, 152 met the inclusion criteria (scheduled for initial treatment with the Stupp protocol, age > 18 years) and 95 tumor samples were suitable for immunohistochemical analysis. The median age is 58 years, (64 men, 34 women). Most of patients received macroscopic (43%) or partial (36%) surgery. In univariate analysis using the Log Rank test, high integrin α5 expression level was associated with poor prognosis (PFS: hazard ratio (HR) = 1,696, p=0,0355; OS: HR=1,598, p = 0,0508). Corresponding median OS were 15,6 versus 19,2 months. Similarly, OS was significantly reduced with age (> 60 years), lower resection degree, higher RPA (recursive partitioning analysis) score and non-methylated MGMT (O-6-methylguanine-DNA methyltransferase) promoter. In the subgroup of patients who received the full initial protocol (temozolomide treatment together with radiotherapy and later as adjuvant treatment; n=58) mean OS was strongly reduced when integrin α5 expression level was high (15,6 versus 22,8 months, p=0,0162) suggesting an impact of integrin signaling on temozolomide response in GBM. CONCLUSION Our study validates for the first time that the high protein level expression of α5 integrin is associated with poor prognosis in GBM. It also confirms its potential as a therapeutic target and its likely role in resistance to temozolomide as previously shown in preclinical study.

scholarly journals CDCA8 as an independent predictor for a poor prognosis in liver cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yu Shuai ◽  
Erxi Fan ◽  
Qiuyue Zhong ◽  
Qiying Chen ◽  
Guangyong Feng ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Liver Cancer ◽  
Poor Prognosis ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Gene Set Enrichment Analysis ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Wilcoxon Rank Sum Test ◽  
Cancer Tissues

Abstract Background Human cell division cycle associated 8 (CDCA8) a key regulator of mitosis, has been described as a potential prognostic biomarker for a variety of cancers, such as breast, colon and lung cancers. We aimed to evaluate the potential role of CDCA8 expression in the prognosis of liver cancer by analysing data from The Cancer Genome Atlas (TCGA). Methods The Wilcoxon rank-sum test was used to compare the difference in CDCA8 expression between liver cancer tissues and matched normal tissues. Then, we applied logistic regression and the Wilcoxon rank-sum test to identify the association between CDCA8 expression and clinicopathologic characteristics. Cox regression and the Kaplan–Meier method were used to examine the clinicopathologic features correlated with overall survival (OS) in patients from the TCGA. Gene set enrichment analysis (GSEA) was performed to explore possible mechanisms of CDCA8 according to the TCGA dataset. Results CDCA8 expression was higher in liver cancer tissues than in matched normal tissues. Logistic regression and the Wilcoxon rank-sum test revealed that the increased level of CDCA8 expression in liver cancer tissues was notably related to T stage (OR = 1.64 for T1/2 vs. T3/4), clinical stage (OR = 1.66 for I/II vs. III/IV), histologic grade (OR = 6.71 for G1 vs. G4) and histological type (OR = 0.24 for cholangiocarcinoma [CHOL] vs. hepatocellular carcinoma [LIHC]) (all P-values < 0.05). Kaplan–Meier survival analysis indicated that high CDCA8 expression was related to a poor prognosis in liver cancer (P = 2.456 × 10−6). Univariate analysis showed that high CDCA8 expression was associated with poor OS in liver cancer patients, with a hazard ratio (HR) of 1.85 (95% confidence interval [CI]: 1.47–2.32; P = 1.16 × 10–7). Multivariate analysis showed that CDCA8 expression was independently correlated with OS (HR = 1.74; CI: 1.25–12.64; P = 1.27 × 10–5). GSEA revealed that the apoptosis, cell cycle, ErbB, MAPK, mTOR, Notch, p53 and TGF-β signaling pathways were differentially enriched in the CDCA8 high expression phenotype. Conclusions High CDCA8 expression is a potential molecular predictor of a poor prognosis in liver cancer.

scholarly journals High Expression of Mediator Complex Subunit 8 Acts as a Prognostic Biomarker in Hepatocellular Carcinoma

2021 ◽  
Author(s):  
Shuang Wu ◽  
Yuan Cao ◽  
Senyuan Luo ◽  
Sancheng Cao ◽  
Qiao Li ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Cycle ◽  
Overall Survival ◽  
Poor Prognosis ◽  
Univariate Analysis ◽  
Cell Cycle Checkpoints ◽  
Gene Set Enrichment Analysis ◽  
Mediator Complex ◽  
Th2 Cells ◽  
Poor Overall Survival

Abstract Background : Mediator complex subunit 8 ( MED8 ) encodes a subunit of the mediator complex ( MED ), which is critical for transcription. MED8 is highly expressed in some tumours and is associated with a poor prognosis. However, correlations between MED8 and clinical features of hepatocellular carcinoma (HCC) have not been reported. Results: A univariate analysis showed that high MED8 expression predicts poor overall survival (HR: 2.495; 95% confidence interval (CI) 1.740, 3.578; P < 0.001). A multivariate regression analysis showed that high MED8 (HR: 3.032 (1.817, 5.060); P < 0.001) expression and M stage (HR=4.075 (1.179-14.091) for M1 vs. M0, P=0.026) are independent prognostic indicator of poor overall survival in patients with HCC. The areas under the curve (AUC) for receiver operating characteristic (ROC) curves were used to describe the prognostic value of MED8 (AUC: 0.905 (0.849, 0.941)). Gene Set Enrichment Analysis (GSEA) and Immune infiltration Analysis were applied to reveal significant enrichment differences among TCGA data. A functional analysis showed that the cell cycle checkpoints, mitotic G2-G2–M phases, transcriptional regulation by TP53, and regulation of TP53 activity were significantly enriched in DEGs associated with high MED8 expression. Th2 cells were positively correlated with MED8 expression. Conclusions: MED8 predicts poor prognosis in HCC, potentially via the regulation of the cell cycle regulation and Th2 cells. Key words: Mediator complex subunit 8, Mediator , hepatocellular carcinoma, prognosis, diagnostic biomarker

scholarly journals Construction of a novel immune-related lncRNA signature and its potential to predict the immune status of patients with hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Min Deng ◽  
Jia-Bao Lin ◽  
Rong-Ce Zhao ◽  
Shao-Hua Li ◽  
Wen-Ping Lin ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Immune Cell ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Penalized Regression ◽  
Clinicopathological Features ◽  
Cutoff Point ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Chemotherapy Drugs

Abstract Background The accuracy of existing biomarkers for predicting the prognosis of hepatocellular carcinoma (HCC) is not satisfactory. It is necessary to explore biomarkers that can accurately predict the prognosis of HCC. Methods In this study, original transcriptome data were downloaded from The Cancer Genome Atlas (TCGA) database. Immune-related long noncoding ribonucleic acids (irlncRNAs) were identified by coexpression analysis, and differentially expressed irlncRNA (DEirlncRNA) pairs were distinguished by univariate analysis. In addition, the least absolute shrinkage and selection operator (LASSO) penalized regression was modified. Next, the cutoff point was determined based on the area under the curve (AUC) and Akaike information criterion (AIC) values of the 5-year receiver operating characteristic (ROC) curve to establish an optimal model for identifying high-risk and low-risk groups of HCC patients. The model was then reassessed in terms of clinicopathological features, survival rate, tumor-infiltrating immune cells, immunosuppressive markers, and chemotherapy efficacy. Results A total of 1009 pairs of DEirlncRNAs were recognized in this study, 30 of these pairs were included in the Cox regression model for subsequent analysis. After regrouping according to the cutoff point, we could more effectively identify factors such as aggressive clinicopathological features, poor survival outcomes, specific immune cell infiltration status of tumors, high expression level of immunosuppressive biomarkers, and low sensitivity to chemotherapy drugs in HCC patients. Conclusions The nonspecific expression level signature involved with irlncRNAs shows promising clinical value in predicting the prognosis of HCC patients.

scholarly journals The relationship between PLOD1 expression level and glioma prognosis investigated using public databases

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11422
Author(s):  
Lei Tian ◽  
Huandi Zhou ◽  
Guohui Wang ◽  
Wen yan Wang ◽  
Yuehong Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Poor Prognosis ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
High Expression ◽  
Expression Level ◽  
Clinicopathologic Characteristics ◽  
Genome Atlas

Background Glioma is the most common type of intracranial tumor with high malignancy and poor prognosis despite the use of various aggressive treatments. Targeted therapy and immunotherapy are not effective and new biomarkers need to be explored. Some Procollagen-lysine 2-oxyglutarate 5-dioxygenase (PLOD) family members have been found to be involved in the metastasis and progression of tumors. Both PLOD2 and PLOD3 had been reported to be highly expressed in gliomas, while the prognostic value of PLOD1 remains to be further illustrated, so we want to investigate the PLOD1 expression in glioma and its clinical implication. Methods We collected gene expression and corresponding clinical data of glioma from the Chinese Glioma Genome Atlas (CGGA) database, The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus (GEO) database. First, we analyzed the expression and mutation of PLOD1 in gliomas and its relationship with clinicopathologic characteristics. Then, we conducted survival analysis, prognostic analysis and nomogram construction of the PLOD1 gene. Finally, we conducted gene ontology (GO) enrichment analysis and gene set enrichment analysis (GSEA) to explore possible mechanisms and gene co-expression analysis was also be performed. Results The results showed that the expression level of PLOD1 was higher in gliomas than normal tissues, and high expression of PLOD1 was related to poor survival which can serve as an oncogenic factor and an independent prognostic indicator for glioma patients. Both the GO and GSEA analysis showed high expression of PLOD1 were enriched in Extracellular matrix (ECM) related pathways, the co-expression analysis revealed that PLOD1 was positively related to HSPG2, COL6A2, COL4A2, FN1, COL1A1, COL4A1, CD44, COL3A1, COL1A2 and SPP1, and high expression of these genes were also correlated to poor prognosis of glioma. Conclusions The results showed that high expression of PLOD1 leads to poor prognosis, and PLOD1 is an independent prognostic factor and a novel biomarker for the treatment of glioma. Furthermore, targeting PLOD1 is most likely a potential therapeutic strategy for glioma patients.

Sign in / Sign up

Export Citation Format

Share Document