Dataset Information

The Role of Prion Protein Expression in Predicting Gastric Cancer Prognosis.

ABSTRACT: Previous reports indicated that prion protein (PrP) is involved in gastric cancer (GC) development and progression, but its role in GC prognosis has been poorly characterized. A total of 480 GC patients were recruited in this retrospective study. PrP expression in cancerous and non-cancerous gastric tissues was detected by using the tissue microarray and immunohistochemical staining techniques. Our results showed that the PrP expression in GC was significantly less frequent than that in the non-cancerous gastric tissue (44.4% vs 66.4%, P < 0.001). Cox regression analysis revealed that PrP expression was associated with TNM stage, survival status and survival time. GC patients with higher TNM stages (stages II, III and IV) had significantly lower PrP expression levels in tumors than those with lower TNM stages (stages 0 and I). Kaplan-Meier survival curves revealed that negative PrP expression was associated with poor overall survival (log-rank test: P < 0.001). The mean survival time for patients with negative PrP expression was significant lower than those with positive PrP expression (43.0±28.5m vs. 53.9±31.1m, P<0.001). In multivariate Cox hazard regression, PrP expression was an independent prognostic factor for GC survival, with a HR (hazard ratio) of 0.687 (95%CI:0.520-0.907, P=0.008). Our results revealed that negative PrP expression could independently predict worse outcome in GC and thereby could be used to guide the clinical practice.

SUBMITTER: Tang Z

PROVIDER: S-EPMC4910591 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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The Role of Prion Protein Expression in Predicting Gastric Cancer Prognosis.

Tang Zhaoqing Z Ma Ji J Zhang Wei W Gong Changguo C He Jing J Wang Ying Y Yu Guohua G Yuan Chonggang C Wang Xuefei X Sun Yihong Y Ma Jiyan J Liu Fenglin F Zhao Yulan Y

Journal of Cancer 20160520 8

Previous reports indicated that prion protein (PrP) is involved in gastric cancer (GC) development and progression, but its role in GC prognosis has been poorly characterized. A total of 480 GC patients were recruited in this retrospective study. PrP expression in cancerous and non-cancerous gastric tissues was detected by using the tissue microarray and immunohistochemical staining techniques. Our results showed that the PrP expression in GC was significantly less frequent than that in the non- ...[more]

PMID: 27313789

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Project description:BackgroundGastric cancer (GC) is one of the most common malignancies. Cuproptosis is a newly discovered type of cell death caused by protein toxicity stress, with copper having considerable importance in GC development.MethodsFirst, differentially expressed (DE) cuproptosis-related genes (CRGs) were screened in GC. The tumor mutation burden (TMB) of CRGs was analyzed. We then performed enrichment analyses of DE-CRGs. Next, we constructed a GC cuproptosis-related (CR) signature (CRs) using Cox and least absolute shrinkage and selection operator (LASSO) regression analyses. The predictive efficacy was assessed using receiver operating characteristic (ROC) curves. Furthermore, we performed gene set enrichment analysis (GSEA). Different methods were used to assess tumor immunity of the CRs, and the Wilcoxon test was used to examine the expressions of m6A-, m7G-, and ferroptosis-related genes. The "pRRophetic" R package (The R Foundation for Statistical Computing) was used to predict the half maximal inhibitory concentration IC50 of common chemotherapeutic agents. Finally, the expression of CRGs in different clusters was analyzed using single-cell RNA sequencing (scRNA-seq).ResultsWe identified 8 DE-CRGs in GC. There were 9 CRGs with TMB values >1%. We constructed gene expression networks and CRs for GC. The DE-CRGs were involved in important mitochondrial metabolic pathways, and the CRs was a valuable independent prognosis factor. The GSEA revealed that angiogenesis and metabolic-related pathways were enriched in the high-risk group, whereas the low-risk group showed enrichment in DNA replication mismatch and repair pathways. The expressions of immunological checkpoints, ferroptosis-, m6A-, and m7G-related genes, type II interferon (INF) response, major histocompatibility complex (MHC class-I), and the IC50 of the copper-based carrier drug elesclomol were significantly different between the 2 groups of the CRs. Furthermore, the scRNA-seq analysis showed that most CRGs were mainly upregulated in endothelial cells.ConclusionsThe novel CRs could predict the prognosis of GC.

Project description:Objective: Immune cells infiltrating has been proved to be associated with prognosis in gastric cancer (GC) by studies. This study aims to explore the prognosis value of infiltrating immune cells in gastric cancer. Methods: In our study, the CIBERSORT algorithm was used to calculate the fraction of 22 tumor-infiltrating immune cells (TIIC) in 100 normal and 300 tumor samples from the GEO cohort and 30 normal and 344 tumor samples from the TCGA cohort. Univariate and multivariate Cox regression were used to construct an immune risk score model. Multivariate cox regression was also used to validate whether our risk score model could predict prognosis in GC independently. Furthermore, the model was validated in different patient subgroups to test its independence. P<0.05 was considered statistically significant. Results: The results showed that the fraction of 3 immune cells increased in tumor tissues compared with normal tissues in both the GEO and TCGA cohort. Univariate cox regression analysis showed four cells significantly correlated with survival rate in GC (P<0.05). The immune risk score model was constructed based on the four cells through multivariate cox regression and further validated. The KM survival curve suggested that patients with high risk had poor prognosis than patients with low risk (P<0.05). ROC curve indicated the model was reliable (AUC= 0.67 in the GEO cohort, AUC = 0.65 in the TCGA cohort). Furthermore, multivariate Cox regression showed the model was an independent factor for overall survival predicting in GC (hazard ratio (HR) = 2.35, 95% confidence interval (CI) = 1.63~3.40 in the GEO cohort, HR = 2.87, 95% CI = 1.94~4.25 in the TCGA cohort). Finally, we validated the model in patient subgroups by the KM survival curve. Conclusion: In summary, tumor-infiltrating immune cells play an essential role in GC progression and affect the outcome of GC patients. The immune risk score can predict overall survival for GC independently, and high immune risk score is associated with poor prognosis.

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Project description: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 < 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.

Dataset Information

The Role of Prion Protein Expression in Predicting Gastric Cancer Prognosis.

Publications

The Role of Prion Protein Expression in Predicting Gastric Cancer Prognosis.

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