High TRAF3IP3 Level Predicts Poor Prognosis of Patients with Gliomas

2020 ◽  
Author(s):  
Guorong Yang ◽  
Shu Tang ◽  
Jie Zhang ◽  
Ling Qin

Abstract Purpose: TRAF3IP3 is involved in the maturation of immune cells, the development of immune tissues and the immune response of the body. TRAF3IP3 is shown to expressed in a variety of malignant tumor cell lines. Down-regulated expression of TRAF3IP3 in malignant melanoma can inhibit tumor growth. However, the role of TRAF3IP3 in glioma is still unknown. In this study, we aimed to study the relationship between TRAF3IP3 and glioma based on TCGA data.Method: We used the Wilcoxon rank sum test to compare the expression of TRAF3IP3 in glioma and normal tissues. Subsequently, Kruskal-Wallis test, Wilcoxon rank sum test, and logistics regression were used to evaluate the relationship between TRAF3IP3 and clinicopathological parameters of glioma patients. GSEA was used to verify the key signal pathways involved in TRAF3IP3. We used the ssGSEA method to analyze the relationship between the expression level of TRAF3IP3 and the immune infiltration in the glioma tumor microenvironment. Finally, we used Kaplan-Meier and COX regression to evaluate the prognostic value of TRAF3IP3.Results: TRAF3IP3 transcription level was highly expressed in gliomas(P<0.001). And the high expression of TRAF3IP3 and WHO grade(OR=3.57(2.42-5.34), P<0.001), IDH status (OR=4.79(3.40-6.83), P<0.001), 1P /19q codeletion (OR=0.07(0.04-0.11), P<0.001), EGFR status (OR=2.77(1.65-4.81), P<0.001), histological type (OR=3.64(2.48-5.43), P<0.001), age (OR=1.64(1.13-2.41), P=0.01), and primary therapy outcome (OR=2.29(1.47-3.61), P<0.001) were significantly correlated. GSEA showed that six signaling pathways were significantly enriched in the TRAF3IP3 high expression phenotype group, including JAK STAT signaling pathway, interferon-γ signaling pathway, apoptosis, P53 signaling pathway, PD-1 signaling pathway, and CTLA4 signaling pathway. ssGSEA showed that the expression of TRAF3IP3 was significantly positively correlated with the infiltration of Macrophages, Th17 cells, etc. Multivariate COX regression showed that TRAF3IP3 was an independent prognostic factor for glioma OS (HR=2.169(1.301-3.615), P=0.003). Kaplan-Meier analysis showed that high expression of TRAF3IP3 was associated with worse PFS(HR=2.39(1.39-3.01), P<0.001), DFS(HR=3.02(2.27-4.01), P<0.001) and OS(HR=2.87(2.20-3.75), P<0.001).Conclusion: TRAF3IP3 may play an important role in the occurrence and development of glioma, and may be a potential biomarker for the diagnosis and prognosis of glioma.

2021 ◽  
Author(s):  
Zhiqiang Yao ◽  
Jiajia Zhang ◽  
Chaohu Chen ◽  
Pan Li ◽  
Jinlong Cao ◽  
...  

Abstract Background: Bladder cancer (BLCA) is the most common malignancy of urinary system with a high recurrence rate. We aimed to explore the relationship between cathepsin V (CTSV) expression and prognosis in patients with bladder cancer.Methods: The RNA-Seq gene expression data and corresponding clinical information with BLCA were downloaded from TCGA database. The gene expression profiles of GSE13507 and GSE133624 were downloaded from GEO database. BLCA patients were divided into high and low expression group according to the cutoff value of CTSV expression. The relationship between clinicopathologic characteristics and CTSV expression was analyzed with the Wilcoxon signed-rank test and logistic regression. Kaplan-Meier analysis and Cox regression were used to analyze the relationship between overall survival and clinicopathologic characteristics. Gene set enrichment analysis (GSEA) was utilized to identify enriched KEGG pathway.Results: High expression of CTSV was significantly correlated with pathological grade (OR = 1.662 for low vs. high), clinical stage (OR = 1.589 for I-II vs. III-IV), status (OR = 1.435 for normal vs. tumor), T stage (OR = 1.589 for T1-2 vs. T3-4), and M stage (OR = 4.499 for M0 vs M1). The expression of CTSV was significantly increased in BLCA compared with normal tissue (P < 0.001). Kaplan-Meier survival analysis showed that BLCA patients with high expression of CTSV had a poorer prognosis than low expression of CTSV patients (P = 0.0016). Univariate Cox analysis showed that high expression of CTSV was significantly associated with poorer overall survival (HR:1.662, 95%CI:1.209-2.286, P = 0.002). Multivariate Cox regression showed that high expression of CTSV was an independent risk factor for poor prognosis in BLCA patients (HR: 1.495, 95%CI: 1.069-2.089, P = 0.019). We also used the GSE13507 and GSE133624 to verify whether CTSV was differently expressed in bladder cancer tissues and normal tissues. The results showed that CTSV expression was significantly increased in BLCA patients (P < 0.05). Finally, GSEA was used to show 22 enriched signaling pathways in a high phenotype.Conclusion: High expression of CTSV in bladder cancer is associated with poor prognosis and may serve as a new biomarker. In addition, the chemokine signaling pathway, MAPK signaling pathway, Wnt signaling pathway, JAK-STAT signaling pathway, tight Junction and cell adhesion molecules may be the key pathway regulated by CTSV in BLCA.


2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Wei Wang ◽  
Shuang Liu ◽  
Chunyi Jiang ◽  
Yan Wang ◽  
Huijun Zhu ◽  
...  

RARβ plays a critical role in cancer progression and is associated with several types of human cancer. It remains unclear, however, whether it is linked to the clinicopathological parameters of colorectal cancer (CRC). We therefore determined the expression of RARβ protein in patients with primary CRC and examined its relationship with clinical outcomes. RARβ expression in 234 samples of CRC patients and matched benign noncancerous tumors was detected by immunohistochemistry. RARβ mRNA expression was confirmed using the TCGA and Oncomine databases. COX regression analysis and Kaplan–Meier survival analysis were performed to determine the relationship between RARβ expression and CRC prognosis. Our results show that high expression of RARβ correlated with better prognosis in CRC patients. RARβ expression in CRC specimens was clearly lower than in peritumoral specimens (30.8% vs 58.8%, p<0.001) and significantly correlated with gender (χ2=3.926, p=0.048), tumor differentiation (χ2=5.978, p=0.014), and tumor stage (χ2=6.642, p=0.036). Multivariate analyses further revealed that low RARβ expression (p=0.001), distant metastasis (p=0.001), tissue differentiation (p=0.006), and tumor stage (p=0.002) were associated with overall survival in CRC patients. In addition, Kaplan–Meier analysis indicated that increased RARβ expression in cytoplasm (p=0.001) and early tumor TNM stage (p=0.030) was associated with a more favorable outcome in patients with CRC. In conclusion, RARβ expression was strongly correlated with several clinicopathological factors of CRC and may represent a favorable prognostic marker in patients with CRC.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Maher Kurdi ◽  
Badrah Alghamdi ◽  
Nadeem Shafique Butt ◽  
Saleh Baeesa

Abstract Background Tumour associated macrophages (TAMs) and tumour infiltrating lymphocytes (TILs) are considered dominant cells in glioblastoma microenvironment. Aim The purpose of this study was to assess the expression of CD204+ M2-polarized TAMs in glioblastomas and their relationship with CD4+TILs, Iba+microglia, and IDH1 mutation. We also exploreed the prognostic value of these markers on the recurrence-free interval (RFI). Methods The expressions of CD204+TAMs, CD4+TILs, and Iba1+microglia were quantitively assessed in 45 glioblastomas using immunohistochemistry. Kaplan–Meier analysis and Cox hazards were used to examine the relationship between these factors. Results CD204+TAMs were highly expressed in 32 tumours (71%) and the remaining 13 tumours (29%) had reduced expression. CD4+TILs were highly expressed in 10 cases (22%) and 35 cases (77.8%) had low expression. There was an inverse correlation between CD204+TAMs and CD4+TILs, in which 85% of tumours had a high expression of CD204+TAMs and a low expression of CD4+TILs. Nevertheless, there was no significant difference in IDH1 mutation status between the two groups (p = 0.779). There was a significant difference in Iba1+microglial activation between IDH1mutant and IDH1wildtype groups (p = 0.031). For cases with a high expression of CD204+TAMs and a low expression of CD4+TILs, there was a significant difference in RFI after treatment with chemoradiotherapy or radiotherapy (p = 0.030). Conclusion Glioblastoma with a dense CD204+TAMs and few CD4+TILs is associated with IDH1wildtype. These findings suggest that TAMs masks tumour cell and suppress T-cell tumoricidal functions via immunomodulatory mechanisms. Blockade of the CD204-TAM receptor may prevent this mechanism and allow the evolution of TILs.


2021 ◽  
Vol 104 (2) ◽  
pp. 003685042110113
Author(s):  
Yusha Chen ◽  
Xiaoqian Lin ◽  
Jinwen Zheng ◽  
Jiancui Chen ◽  
Huifeng Xue ◽  
...  

Apelin (APLN) is recently demonstrated a direct association with many malignant diseases. However, its effects on cervical cancer remain unclear. This study therefore aims to evaluate the association between APLN expression and cervical cancer using publicly available data from The Cancer Genome Atlas (TCGA). The Pearson χ2 test and Fish exact test, as well as logistic regression, were used to evaluate the relationship between clinicopathological factors in cervical cancer and the expression of APLN. Additionally, the Cox regression and Kaplan-Meier methods were conducted to analyze the Overall Survival (OS) of cervical cancer patients in TCGA. Finally, gene set enrichment analysis (GSEA) was performed to establish its biological functions. High expression of APLN in cervical cancer was significantly associated with a more advanced clinical stage (OR = 1.91 (1.21–3.05) for Stage II, Stage III, and Stage IV vs Stage I, p = 0.006). Additionally, it was associated with poor outcome after primary therapy (OR = 2.14 (1.03–4.59) for Progressive Disease (PD), Stable Disease (SD), and Partial Response (PR) vs Complete Remission (CR), p = 0.045) and high histologic grade (OR = 1.67 (1.03–2.72) for G3 and G4 vs G1 and G2, p = 0.037). Moreover, multivariate analysis showed that high expression of APLN was associated with a shorter OS. GSEA demonstrated that six KEGG pathways, including PPAR signaling, ECM-receptor interaction, focal adhesion, MAPK signaling, TGF-beta signaling, and Gap junction pathways were differentially enriched in the high expression APLN phenotype. The recent study suggests that APLN plays an important role in the progression of cervical cancer and might be a promising prognostic biomarker of the disease.


2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Ji-sheng Jing ◽  
Hongbo Li ◽  
Shun-cai Wang ◽  
Jiu-ming Ma ◽  
La-qing Yu ◽  
...  

N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan–Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan–Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.


2021 ◽  
Author(s):  
Yanghui Wen ◽  
Hui Su ◽  
Wuke Wang ◽  
Feng Ren ◽  
Haitao Jiang ◽  
...  

Abstract Background: NBEAL2 is a member of the BEACH domain–containing protein (BDCP) family and little is known about the relationship between NBEAL2 and malignancy.Methods: We downloaded the Gene expression profiles and clinical data of Liver hepatocellular carcinoma(LIHC) form the Cancer Genome Atlas (TCGA) dataset. The expression difference of NBEAL2 in LIHC tissues and adjacent nontumor tissues was analyzed by R software. The relationship between NBEAL2 expression and clinicopathological parameters was evaluate by Chi-square test. The effect of NBEAL2 expression on survival were assessed by Kaplan–Meier survival analysis and Cox proportional hazards regression model. GSEA was used to explore the potential molecular mechanism of NBEAL2 in LIHC.Results: Up-regulation of NBEAL2 expression was detected in the LIHC tissue compared with adjacent nontumor tissues(P < 0.001). The chi-square test showed that no significant correlation between the expression level of NBEAL2 and various clinicopathological parameters (including T, N and M classifications) were detected. The Kaplan–Meier curves suggested that lower NBEAL2 expression was related with poor prognosis. The results of Multivariate analysis revealed that a lower expression of NBEAL2 in LIHC was an independent risk of poor overall survival (HR, 8.873; 95% CI, 1.159-67.936; P = 0.035). GSEA suggested that multiple tumor-related metabolic pathways were evidently enriched in samples with the low-NBEAL2 expression phenotype. Conlusion: NBEAL2 might act as an tumor suppressor gene in the progression of LIHC but the precise role of NBELA2 in LIHC needs further vertification.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiangye Liu ◽  
Tingting Li ◽  
Delong Kong ◽  
Hongjuan You ◽  
Fanyun Kong ◽  
...  

Abstract Background Hepatocellular carcinoma (HCC) is a malignancy with high incidence and mortality rates worldwide. Alcohol dehydrogenases (ADHs) are huge family of dehydrogenase enzymes and associated with the prognosis of various cancers. However, comprehensive analysis of prognostic implications related to ADHs in HCC is still lacking and largely unknown. Methods The expression profiles and corresponding clinical information of HCC were obtained from The Cancer Genome Atlas (TCGA). Wilcoxon signed-rank test was employed to evaluate the expression of ADHs. Cox regression and Kaplan-Meier analyses were used to investigate the association between clinicopathological characteristics and survival. GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analyses were performed and visualized using R/BiocManager package. Results We found that the expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 was significantly downregulated in HCC samples compared to normal liver samples. Our univariate and multivariate Cox regression analyses results showed that high expression of ADH1A, ADH1B, ADH1C, ADH4, and ADH6 was considered as an independent factor with an improved prognosis for the survival of HCC patients. Moreover, our Kaplan-Meier analysis results also revealed that high expression of AHD1A, ADH1B, ADH1C, ADH4, and ADH6 was significantly associated with good survival rate in HCC patients. In addition, GO, KEGG, and GSEA analyses unveiled several oncogenic signaling pathways were negatively associated high expression of ADHs in HCC. Conclusion In the present study, our results provide the potential prognostic biomarkers or molecular targets for the patients with HCC.


2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Hai-Ge Zhang ◽  
Ping Yang ◽  
Tao Jiang ◽  
Jian-Ying Zhang ◽  
Xue-Juan Jin ◽  
...  

Purpose. To investigate whether lymphocyte nadir induced by radiation is associated with survival and explore its underlying risk factors in patients with hepatocellular carcinoma (HCC). Methods. Total lymphocyte counts were collected from 184 HCC patients treated by radiotherapy (RT) with complete follow-up. Associations between gross tumor volumes (GTVs) and radiation-associated parameters with lymphocyte nadir were evaluated by Pearson/Spearman correlation analysis and multiple linear regression. Kaplan–Meier analysis, log-rank test, as well as univariate and multivariate Cox regression were performed to assess the relationship between lymphocyte nadir and overall survival (OS). Results. GTVs and fractions were negatively related with lymphocyte nadir (p<0.001 and p=0.001, respectively). Lymphocyte nadir and Barcelona Clinic Liver Cancer (BCLC) stage were independent prognostic factors predicting OS of HCC patients (all p<0.001). Patients in the GTV ≤55.0 cc and fractions ≤16 groups were stratified by lymphocyte nadir, and the group with the higher lymphocyte counts (LCs) showed longer survival than the group with lower LCs (p<0.001 and p=0.006, respectively). Patient distribution significantly differed among the RT fraction groups according to BCLC stage (p<0.001). However, stratification of patients in the same BCLC stage by RT fractionation showed that the stereotactic body RT (SBRT) group achieved the best survival. Furthermore, there were significant differences in lymphocyte nadir among patients in the SBRT group. Conclusions. A lower lymphocyte nadir during RT was associated with worse survival among HCC patients. Smaller GTVs and fractions reduced the risk of lymphopenia.


2020 ◽  
Vol 19 ◽  
pp. 153303382097754
Author(s):  
Rongchang Zhao ◽  
Dan Ding ◽  
Wenyan Yu ◽  
Chunrong Zhu ◽  
Yan Ding

Background: As a common pathological type of lung cancer, lung adenocarcinoma (LUAD) is mainly treated by surgery, chemotherapy, targeted therapy and radiotherapy. Although a relatively mature treatment system has been established, there are few studies on the microenvironment of LUAD. Material and Methods: The immune and stromal scores of patients from the LUAD cohort in the TCGA database were obtained by using ESTIMATE. The relationship of immune and stromal scores with the clinicopathological characteristics and overall survival of LUAD patients was assessed by R. GO, KEGG and Cox regression analyses were employed to analyze intersecting genes and to identify reliable prognostic markers. The identified genes were also analyzed in the GEPIA database to assess their correlations with survival, and these relationships were verified with the Kaplan-Meier Plotter database. Results: The immune score was related to the survival time and tumor topography of LUAD patients. There was a significant correlation between stromal score and tumor metastasis. Through multivariate analysis, stage (HR = 1.640, 95% CI = 1.019-2.642, P = 0.042) and risk score (HR = 1.036, 95% CI = 1.026-1.046, P < 0.001). The genes (ARHGAP15, BTLA, CASS4, CLECL1, FAM129C, STAP1, TESPA1, and S100P) showed credible prognostic value in LUAD patients in TCGA through GEPIA database online analysis and verification in the Kaplan-Meier plotter database. Conclusions: In the microenvironment of lung adenocarcinoma, the differentially expressed genes screened by immune score and stromal score have certain value in evaluating the survival/prognosis of patients, as well as the invasion and progression of tumors.


2010 ◽  
Vol 2010 ◽  
pp. 1-5 ◽  
Author(s):  
Winnie S. Su ◽  
Catherine M. Clase ◽  
K. Scott Brimble ◽  
Peter J. Margetts ◽  
Trevor J. Wilkieson ◽  
...  

Objectives. The primary objective of this study was to determine the relationship between waist-to-hip ratio (WHR), cardiovascular (CV) events, and mortality in peritoneal dialysis (PD) patients. A secondary objective was to investigate the association between abdominal obesity and systemic inflammatory markers.Methods. This is a prospective study of 22 prevalent PD patients. WHR was measured at baseline. C-reactive protein (CRP), tumour necrosis factor-α(TNF-α), and interleukin-6 (IL-6) were measured. Main outcomes were first CV event and death from all causes. Survival analysis was used to examine the relationship between anthropomorphic measures and clinical outcomes.Results. Mean follow-up period was 3.1 years. In Kaplan-Meier analysis, survival was lower in those with higher WHR (P=.002). In Cox regression, WHR independently predicted mortality and first CV event after adjustment for known ischemic heart disease (hazard ratio [HR] 1.17, confidence interval [CI] 1.05–1.30 for death; HR 1.13, CI 1.01–1.26 for CV event). WHR correlated with serum TNF-α(r=0.45;P=.05).Conclusion. The results of this study suggest WHR may be a risk factor for increased CV events and mortality in PD patients. Abdominal obesity is also associated with inflammatory markers. Larger studies are warranted to confirm these findings.


Sign in / Sign up

Export Citation Format

Share Document