scholarly journals TBL1XR1 Is Highly Expressed in Gastric Cancer and Predicts Poor Prognosis

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Fang Liu ◽  
Yuan He ◽  
Qinghua Cao ◽  
Ni Liu ◽  
Wenhui Zhang
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Cox Regression ◽  
Biological Significance ◽  
High Expression ◽  
Human Gastric Cancer ◽  
Mrna Levels ◽  
Poor Overall Survival ◽  
Cox Regression Analysis

Objective. To investigate the expression of transducin- (β-) like 1 X-linked receptor 1 (TBL1XR1) in human gastric cancer (GC) and its correlation with prognostic and biologic significance.Methods. TBL1XR1 mRNA expression was analyzed in gastric cancer using a microarray dataset (GSE2701) from the Gene Expression Omnibus (GEO). Immunohistochemistry (IHC) analysis of TBL1XR1 was performed on GC tissue microarray (TMA) to assess its prognostic and biological significance in 334 patients of GC.Results. Analysis of GSE2701 showed that the mRNA levels of TBL1XR1 were significantly elevated in primary gastric tumor and lymph node tissues than normal gastric tissues (P<0.05). The same results of TBL1XR1 protein level were observed by IHC staining in 334 GC tissues. 204 of 334 (60.1%) primary gastric cancer tissues showed high expression of TBL1XR1 protein. TBL1XR1 overexpression was significantly correlated with lymph node metastasis (P=0.000) and advanced TNM stage (P=0.001). Moreover, high levels of TBL1XR1 predicted worse overall survival (P=0.015). Multivariate Cox regression analysis indicated that high expression of TBL1XR1 was an independent prognostic factor for poor overall survival (HR, 0.525; 95% confidence interval, 0.367–0.752;P=0.005).Conclusion. This present study demonstrates that TBL1XR1 is overexpressed in gastric cancer and may be a potential predictor and therapeutic target for GC patients.

The Clinicopathological Significance and Prognostic Value of Obg-Like Atpase 1 (OLA1) in Gastric Cancer

2021 ◽  
Author(s):  
Juan Wang ◽  
Zihan Zheng ◽  
Qinghua Cao ◽  
Xiufen Liu ◽  
Zhiqing Wang
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Prognostic Value ◽  
Biological Significance ◽  
High Expression ◽  
Cancer Tissue ◽  
Cox Regression Analysis ◽  
Gastric Cancer Patients ◽  
Cancer Tissues

Abstract Backgroud Obg-like ATPase 1 (OLA1) is a member of the Obg family of P-loop NTPases and has recently been detected in several human cancer cells. However, its expression type and clinical relevance in gastric cancer remains unclear. Methods In the present study, 2 datasets downloaded from the open Gene Expression Omnibus database were used to evaluate the mRNA level of OLA1 in gastric cancer. Quantitative Reverse Transcription PCR further validated the mRNA expression in gastric cancer tissues. Immunohistochemistry was performed on gastric cancer tissue microarray to assess OLA1 protein expression type, prognostic value, biological significance and its association with Snail in 334 patients of gastric cancer. The prognostic value of combination of OLA1 and Snail has been evaluated. Results The results showed that OLA1 mRNA and protein were elevated in gastric cancer tissues. High expression of OLA1 was significantly associated with aggressive features, such as tumor size, lymph node metastasis and TNM stage (P = 0.0146, P = 0.0037, P < 0.001, respectively). Moreover, high levels of OLA1 predicted worse overall survival. Multivariate Cox regression analysis indicated that high expression of OLA1 was an independent prognostic factor for poor overall survival (hazard ratio, 0.573; 95% confidence interval, 0.376–0.872; P = 0.009). Additionally, OLA1 expression was positively correlated with Snail, and combination of them revealed improved prognostic accuracy for gastric cancer patients. Conclusions Our results suggested that OLA1 high expression was considered as an independent factor for the prediction of unfavorable prognosis in gastric cancer patients, and we believe that OLA1 could serve as a biomarker of poor prognosis and a novel target in treating gastric cancers.

scholarly journals Identification of the angiogenesis related genes for predicting prognosis of patients with gastric cancer

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Sheng Zheng ◽  
Zizhen Zhang ◽  
Ning Ding ◽  
Jiawei Sun ◽  
Yifeng Lin ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
High Efficiency ◽  
Cox Regression ◽  
Risk Group ◽  
The Cancer Genome Atlas ◽  
Differentially Expressed ◽  
Lasso Regression ◽  
Sequencing Data ◽  
Cox Regression Analysis

Abstract Introduction Angiogenesis is a key factor in promoting tumor growth, invasion and metastasis. In this study we aimed to investigate the prognostic value of angiogenesis-related genes (ARGs) in gastric cancer (GC). Methods mRNA sequencing data with clinical information of GC were downloaded from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases. The differentially expressed ARGs between normal and tumor tissues were analyzed by limma package, and then prognosis‑associated genes were screened using Cox regression analysis. Nine angiogenesis genes were identified as crucially related to the overall survival (OS) of patients through least absolute shrinkage and selection operator (LASSO) regression. The prognostic model and corresponding nomograms were establish based on 9 ARGs and verified in in both TCGA and GEO GC cohorts respectively. Results Eighty-five differentially expressed ARGs and their enriched pathways were confirmed. Significant enrichment analysis revealed that ARGs-related signaling pathway genes were highly related to tumor angiogenesis development. Kaplan–Meier analysis revealed that patients in the high-risk group had worse OS rates compared with the low-risk group in training cohort and validation cohort. In addition, RS had a good prognostic effect on GC patients with different clinical features, especially those with advanced GC. Besides, the calibration curves verified fine concordance between the nomogram prediction model and actual observation. Conclusions We developed a nine gene signature related to the angiogenesis that can predict overall survival for GC. It’s assumed to be a valuable prognosis model with high efficiency, providing new perspectives in targeted therapy.

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 Development and Validation of a Unique Gignature of Cancer Stemness-related Genes for Predicting the Overall survival of Colorectal Cancer Patients

2020 ◽  
Author(s):  
Ran Wei ◽  
Jichuan Quan ◽  
Shuofeng Li ◽  
Zhao Lu ◽  
Xu Guan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
The Cancer Genome Atlas ◽  
Cancer Stemness ◽  
Poor Overall Survival ◽  
Tissue Samples ◽  
Cox Regression Analysis ◽  
Rna Methylation ◽  
M6a Rna Methylation

Abstract Background: Cancer stem cells (CSCs), which are characterized by self-renewal and plasticity, are highly correlated with tumor metastasis and drug resistance. To fully understand the role of CSCs in colorectal cancer (CRC), we evaluated the stemness traits and prognostic value of stemness-related genes in CRC.Methods: In this study, the data from 616 CRC patients from The Cancer Genome Atlas (TCGA) were assessed and subtyped based on the mRNA expression-based stemness index (mRNAsi). The correlations of cancer stemness with the immune microenvironment, tumor mutational burden (TMB) and N6-methyladenosine (m6A) RNA methylation regulators were analyzed. Weighted gene co-expression network analysis (WGCNA) was performed to identify the crucial stemness-related genes and modules. Furthermore, a prognostic expression signature was constructed using Lasso-penalized Cox regression analysis. The signature was validated via multiplex immunofluorescence staining of tissue samples in an independent cohort of 48 CRC patients.Results: This study suggests that high mRNAsi scores are associated with poor overall survival in stage Ⅳ CRC patients. Moreover, the levels of TMB and m6A RNA methylation regulators were positively correlated with mRNAsi scores, and low mRNAsi scores were characterized by increased immune activity in CRC. The analysis identified 2 key modules and 34 key genes as prognosis-related candidate biomarkers. Finally, a 3-gene prognostic signature (PARPBP, KNSTRN and KIF2C) was explored together with specific clinical features to construct a nomogram, which was successfully validated in an external cohort. Conclusions: There is a unique correlation between CSCs and the prognosis of CRC patients, and the novel biomarkers related to cell stemness could accurately predict the clinical outcomes of these patients.

scholarly journals Opposite roles of BAP1 in overall survival of uveal melanoma and cutaneous melanoma

2019 ◽  
Author(s):  
Feng Liu-Smith
Keyword(s):  
Overall Survival ◽  
Uveal Melanoma ◽  
Cutaneous Melanoma ◽  
Cox Regression ◽  
Survival Function ◽  
Poor Overall Survival ◽  
Cox Regression Analysis ◽  
Oncogenic Pathways ◽  
Cellular Context ◽  
Age Of Diagnosis

Abstract Background: BAP1 germline mutations predispose individuals to a number of cancer types including uveal melanoma (UM) and cutaneous melanoma (CM) which are distinctively different in the oncogenic pathways. BAP1 loss was common in UM and was associated with a worse prognosis. BAP1 loss was rare in CM and the outcome was unclear. Methods: This study used TCGA UM and CM databases for survival analysis for patients with different BAP1 status and mRNA expression levels. Cox regression model was used for adjusting to known prognosis factors. Results: BAP1- (loss or low expression) predicted a poor overall survival in UM (Cox HR = 0.062, logrank p =0.007) but a contrasting better overall survival in CM (HR = 1.69, p =0.009). Multi-covariate Cox regression analysis indicated BAP1 was a significant predictor for overall survival after adjusting for age of diagnosis, presence of ulceration, Breslow depth and CM stages in patients older than 50 years but not in younger patients. Co-expression analysis revealed no shared genes in BAP1 altered UM and CM tumors, further supporting a completely distinctive role of BAP1 in CM and UM. Conclusions: low BAP1 mRNA was significantly associated with a better overall survival in CM patients, in sharp contrast to its tumor suppressor role in UM where low or loss of BAP1 indicated a worse overall survival. Function of BAP1 may be dependent on cellular context.

The prognostic impact of hypoxia-inducible factor-1α and VEGF, IGF-2, p21, p53 expression in gastric adenocarcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4571-4571
Author(s):  
Y. Kakeji ◽  
K. Mizokami ◽  
Y. Sumiyoshi ◽  
K. Yoshinaga ◽  
H. Saeki ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Growth Factor ◽  
Cox Regression ◽  
Hypoxia Inducible Factor ◽  
Depth Of Invasion ◽  
Human Gastric Cancer ◽  
Prognostic Impact ◽  
P53 Expression ◽  
Cox Regression Analysis ◽  
Dismal Prognosis

4571 Background: Hypoxia caused by either radiation or chemotherapy induces various intracellular adaptive responses, which contribute to tumor progression. The clinicopathological characteristics of human gastric cancer and the clinical outcomes were analyzed to investigate the effects of the expression of hypoxia-inducible factor1α (HIF-1α) and some related proteins, such as, vascular endothelial growth factor (VEGF), insulin-like growth factor-2 (IGF-2), p21, and p53 on the prognosis of human gastric cancer. Methods: The expressions of HIF-1α, VEGF, IGF-2, p21, and p53 proteins were determined by immunohistochemistry in 216 specimens of primary gastric cancer. Results: Of all 216 patients, 85 (39.4%) showed a positive expression of HIF-1α. In addition, the HIF-1α expression positively correlated with the tumor size and depth of invasion, while it was also more frequent in tumors with lymphatic invasion and undifferentiated adenocarcinomas. Though the VEGF expression significantly correlated with the HIF-1α expression, the expressions of IGF-2, p21 and p53 did not show any correlation. HIF-1α-positive/p21-negative tumors had a lower apoptotic index, and the patients with such tumors also had a significantly poorer prognosis. Similarly, HIF-1α-positive/p53-positive tumors had a significantly poorer prognosis. A multivariate Cox regression analysis showed the depth of invasion, lymph node metastasis, and HIF-1α positivity to all be independent prognostic factors in patients with gastric cancer. Conclusions: Based on the above findings, HIF-1α is therefore considered to be a useful independent prognostic factor in gastric cancer, and the combination of a HIF-1α protein overexpression with the loss of p21 expression or nonfunctional p53 thus tends to indicate a dismal prognosis. Controlling hypoxia, especially in the HIF-1α pathways, may therefore hold the key to a greater individualization of therapy and also lead to the development of new treatments for patients with gastric cancer. No significant financial relationships to disclose.

scholarly journals Integrated Analysis of lncRNA-Associated ceRNA Network Identifies Two lncRNA Signatures as a Prognostic Biomarker in Gastric Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-16
Author(s):  
Shuyan Zhang ◽  
Shanshan Li ◽  
Jian-Lin Guo ◽  
Ningyi Li ◽  
Cai-Ning Zhang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Cox Proportional Hazards ◽  
Integrated Analysis ◽  
Survival Prediction ◽  
Survival Prognosis ◽  
Cox Regression Analysis ◽  
Cerna Network

Background. Gastric cancer (GC) is a malignant tumour that originates in the gastric mucosal epithelium and is associated with high mortality rates worldwide. Long noncoding RNAs (lncRNAs) have been identified to play an important role in the development of various tumours, including GC. Yet, lncRNA biomarkers in a competing endogenous RNA network (ceRNA network) that are used to predict survival prognosis remain lacking. The aim of this study was to construct a ceRNA network and identify the lncRNA signature as prognostic factors for survival prediction. Methods. The lncRNAs with overall survival significance were used to construct the ceRNA network. Function enrichment, protein-protein interaction, and cluster analysis were performed for dysregulated mRNAs. Multivariate Cox proportional hazards regression was performed to screen the potential prognostic lncRNAs. RT-qPCR was used to measure the relative expression levels of lncRNAs in cell lines. CCK8 assay was used to assess the proliferation of GC cells transfected with sh-lncRNAs. Results. Differentially expressed genes were identified including 585 lncRNAs, 144 miRNAs, and 2794 mRNAs. The ceRNA network was constructed using 35 DElncRNAs associated with overall survival of GC patients. Functional analysis revealed that these dysregulated mRNAs were enriched in cancer-related pathways, including TGF-beta, Rap 1, calcium, and the cGMP-PKG signalling pathway. A multivariate Cox regression analysis and cumulative risk score suggested that two of those lncRNAs (LINC01644 and LINC01697) had significant prognostic value. Furthermore, the results indicate that LINC01644 and LINC01697 were upregulated in GC cells. Knockdown of LINC01644 or LINC01697 suppressed the proliferation of GC cells. Conclusions. The authors identified 2-lncRNA signature in ceRNA regulatory network as prognostic biomarkers for the prediction of GC patient survival and revealed that silencing LINC01644 or LINC01697 inhibited the proliferation of GC cells.

scholarly journals KK-LC-1 may be an effective prognostic biomarker for gastric cancer

2020 ◽  
Author(s):  
Jun Ji ◽  
Jiahui Chen ◽  
Anqiang Wang ◽  
Wei Zhang ◽  
Hongge Ju ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Cox Regression ◽  
Staining Intensity ◽  
Good Prognosis ◽  
Clinicopathological Parameters ◽  
Chi Square ◽  
Clinical Prognosis ◽  
Cox Regression Analysis ◽  
Normal Tissues

Abstract Background: To detect the expression of Kita-Kyushu lung cancer antigen-1 (KK-LC-1) in gastric cancer (GC) specimens and analyze the associations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis. Methods: A total of 94 patients with GC who underwent surgical resection were enrolled in this study. The expression of KK-LC-1 in GC tissues was detected by immunohistochemistry. The assessment of KK-LC-1 expression was conducted using the H-scoring system. H-score was calculated by the multiplication of the overall staining intensity with the percentage of positive cells. The expression of KK-LC-1 in the cytoplasm and was scored to achieve respective H-score values. The correlations between KK-LC-1 expression and clinicopathological parameters and clinical prognosis were analyzed using Chi-square test, Kaplan-Meier method and Cox regression. Results: In the cytoplasm, the expression of KK-LC-1 in tumor tissues was significantly higher than that in normal tissues (P < 0.001, respectively). Using the median H-score as the cutoff value, it was discovered that, GC patients with higher levels of KK-LC-1expression in the cytoplasm, had favorable overall survival (P =0.016), and it was still statistically meaningful in Cox regression analysis. At the same time, the study found that there was a negative correlation between KK-LC-1’s protein expression and the pathological grade of the tumor (P = 0.036). Conclusions: Our research data shows that KK-LC-1’s expression in GC is higher than that of normal tissues, which is associated with a longer overall survival in GC. KK-LC-1 can be used as a biomarker for GC patients with good prognosis.

scholarly journals High Expression of PABPC1 Predicts Worse Survival of Gastric Cancer Patients

2020 ◽  
Author(s):  
Tailai An ◽  
Lingna Deng ◽  
Zheng Yang ◽  
Cuicui Chai ◽  
Yan Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Regression Analysis ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Mrna Translation ◽  
High Expression ◽  
Depth Of Invasion ◽  
Cox Regression Analysis

Abstract Background: Gastric cancer (GC) is one of the most common cancers with one of the highest mortality rates. Unfortunately, underlying molecular mechanisms contributing to GC have not been fully illuminated. PABPC1 is involved in a series of processes, such as mRNA translation, and mRNA deadenylation and decay. We performed this study to clarify the role of PABPC1 in GC. Methods: To evaluate PABPC1 expressions in GC and normal tissues, we performed bioinformatics analysis of data from TCGA. PABPC1 expressions were evaluated by immunohistochemical (IHC) staining of 170 GC specimens. Associations between PABPC1 expression and clinicopathological variables were analyzed. Independent predictive factors for survival of GC patients were determined by Cox regression analysis. Results: It was revealed by bioinformatics analysis that compared with normal gastric tissues, PABPC1 expressions in GC tissues were significantly higher (P=0.002, paired) (P=3.605e^-9, unpaired). It was revealed that PABPC1 expression was significantly associated with tumor size (P=0.008), Borrmann classification (P=0.003), vessel invasion (P=0.017), depth of invasion (P=0.032), lymph node metastasis (P=0.001), and TNM stage (P=0.019). It was demonstrated through Cox regression analysis that PABPC1 expression was a predictive factor for both overall survival (OS) (P<0.001) and disease-free survival (DFS) (P<0.001) of GC patients. Conclusions: Compared with that of normal gastric tissue, expression level of PABPC1 in GC tissue was significantly higher and PABPC1,s high expression was significantly associated with poorer survival, suggesting its potential as a therapeutic biomarker for GC.

Early gastric cancer: The importance of early diagnosis on prognosis of gastric carcinoma.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 29-29 ◽  
Author(s):  
T. Bouca-Machado ◽  
H. Santos Sousa ◽  
E. Lima-da-costa ◽  
J. Pinto-de-Sousa ◽  
J. Preto ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lymph Node ◽  
Early Gastric Cancer ◽  
Gastric Carcinoma ◽  
Early Diagnosis ◽  
Cox Regression ◽  
Gastroesophageal Junction ◽  
Venous Invasion ◽  
Cox Regression Analysis ◽  
Advanced Tumors

29 Background: The aim of this study was to evaluate the characteristics of early gastric cancer (EGC) in comparison to advanced tumors and its role in patient's prognosis. Methods: This study was related to 1,272 patients admitted with gastric or gastroesophageal junction carcinoma in our department, between January 1988 and December 2008. During this period the incidence of EGC was 12.68% (3.62% T0, 42.75% T1a and 53.62% T1b). Several clinical, pathological and staging parameters were evaluated according to classification in EGC and advanced tumors. Results: Significant differences were observed in location (p<0.001); type of resection surgery (p<0.001) and of lymphadenectomy (p=0.008 for Siewert and p<0.001 for Japanese classifications) with less radical surgery in EGC patients. This type of tumors presented characteristics associated with a better prognosis in the following pathological parameters: tumor dimensions (p<0.001), macroscopic form (p<0.001), Ming's classification (p<0.001), venous invasion (p<0.001) and lymphatic permeation (p<0.001). The 5-year survival rate of this series was 33.7%. There were significant differences in survival curves according to classification in EGC and advanced tumors (73% at 5 years and 26% at 5 years, respectively). Cox-regression analysis identified age, T and lymph node ratio as independent prognostic factors. There was no significant differences in age (cut-off 45 years), but there was significant differences in lymph node metastasis (p<0.001). In 23.87% of EGC there was lymph node involvement, with significant differences (p=0.002) according to the depth wall invasion [T0 (100% N0), T1a (91.5% N0, 8.5% N1), T1b (60.8% N0, 21.6% N1, 13.5% N2, 4.1% N3a)]. Conclusions: The EGC percentage in our series was lower in comparison with other countries with high incidence of gastric cancer. The prognosis of the patients with gastric carcinoma continues to be gloomy mainly due to the late diagnosis and, given that the surgical treatment doesn't seem plausible of achieving a margin of significant additional progression, the need for an early diagnosis emerges if an improvement in patient survival is desired. No significant financial relationships to disclose.

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