scholarly journals Predictive value of the serum RASSF10 promoter methylation status in gastric cancer

2019 ◽  
Vol 47 (7) ◽  
pp. 2890-2900 ◽  
Author(s):  
Yilin Hu ◽  
Peng Ma ◽  
Ying Feng ◽  
Peng Li ◽  
Hua Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Promoter Methylation ◽  
Cox Regression ◽  
Methylation Status ◽  
Disease Free Survival ◽  
Prognostic Indicator ◽  
Chronic Atrophic Gastritis ◽  
Survival Times ◽  
Cox Regression Analysis ◽  
Specific Pcr

Background This study aimed to investigate whether the detection of methylation in the promoter of the Ras association domain family 10 gene ( RASSF10) in the serum of patients with gastric cancer (GC) by methylation-specific PCR (MSP) can be used as a diagnostic and prognostic indicator of GC. Methods We used MSP to examine RASSF10 methylation levels in the serum and/or tumor samples from 100 GC patients, 50 patients with chronic atrophic gastritis (CAG), and 45 healthy controls (HC). We also analyzed clinicopathological and follow-up data. Results Our results showed that the rate of serum RASFF10 promoter methylation among patients with GC (49/100) was higher than in those with CAG (1/50) or HC (0/45). Moreover, the RASSF10 methylation status was consistent between serum and tumor tissues. GC patients with serum RASSF10 promoter methylation had significantly shorter overall survival and disease-free survival times than GC patients without serum RASSF10 promoter methylation. Multivariable Cox regression analysis showed that serum RASSF10 promoter methylation and lymph node metastasis both correlated with reduced survival in GC patients. Conclusions Detection of the serum RASSF10 methylation status by MSP is feasible as a diagnostic and prognostic indicator of GC.

scholarly journals The Diagnosis Value of Promoter Methylation of UCHL1 in the Serum for Progression of Gastric Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Gongping Wang ◽  
Wei Zhang ◽  
Bo Zhou ◽  
Canhui Jin ◽  
Zengfang Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Promoter Methylation ◽  
Poor Prognosis ◽  
Methylation Status ◽  
Tumor Stage ◽  
Chronic Atrophic Gastritis ◽  
Dependent Manner ◽  
Specific Pcr ◽  
And Control

Background.Aberrant promoter methylation has been considered as a potential molecular marker for gastric cancer (GC). However, the role of methylation of FLNC, THBS1, and UCHL1 in the development and progression of GC has not been explored.Methods.The promoter methylation status of UCHL1, FLNC, THBS1, and DLEC1 was assessed by quantitative methylation-specific PCR (QMSP) in the serum of 82 GC patients, 46 chronic atrophic gastritis (CAG) subjects, and 40 healthy controls.Results.All four genes had significantly higher methylation levels in GC patients than in CAG and control subjects. However, only UCHL1 methylation was significantly correlated with the tumor stage and lymph node metastasis. While THBS1 methylation was altered in an age-dependent manner, FLNC methylation was correlated with differentiation andHelicobacter pyloriinfection. DLEC1 methylation was only associated with tumor size. Moreover, methylated UCHL1 with or without THBS1 in the serum was found to be significantly associated with a poor prognosis.Conclusion.The promoter methylation degree of FLNC, THBS1, UCHL1, and DLEC1 in serum could tell the existence of GC and only UCHL1 in the serum was also associated with poor prognosis of GC.

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.

scholarly journals P2X7R as an independent prognostic indicator in gastric cancer

2020 ◽  
Author(s):  
Ilknur Calik ◽  
Muhammet Calik ◽  
Burcu Sarikaya ◽  
Ibrahim Hanifi Ozercan ◽  
Ramazan Arslan ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cox Regression ◽  
Tumor Infiltrating Lymphocytes ◽  
Prognostic Indicator ◽  
P2x Receptor ◽  
Depth Of Invasion ◽  
Human Gastric Cancer ◽  
Free Oxygen Radicals ◽  
Cox Regression Analysis ◽  
Prognostic Parameter

Gastric cancer is one of the foremost causes of cancer related death around the world. The P2X7 receptor (P2X7R), a member of the P2X receptor subfamily of P2 receptors, is a unique molecule that has been shown to affect tumor growth and progression as well as various inflammatory processes, including proliferation of T lymphocytes, release of cytokines, and production of free oxygen radicals. P2X7R has been established as a prognostic parameter in some cancers and, recently, it has been investigated in the development of new targeted therapies. In the present study, we aimed to investigate the prognostic value of P2X7R expression in GC. The expression profile of P2X7R was evaluated immunohistochemically in 156 paraffin-embedded human gastric cancer specimens. P2X7R expression was higher in patients with lymph node metastasis than in those without (p < 0.001). P2X7R overexpression was closely related with tumor-infiltrating lymphocytes [TILs] (p = 0.001), vascular invasion (p = 0.006), depth of invasion (p < 0.001), distant metastasis (p < 0.001), and advanced TNM stage (p < 0.001). Moreover, univariate (HR 3.98; 95% CI 1.89–11.82; p < 0.001) and multivariate (HR 2.24; 95% CI 3.53–12.50; p < 0.001) Cox regression analysis showed that upregulated P2X7R expression clearly correlated with worsened overall survival. In summary, our data revealed that P2X7R may serve as a reliable prognostic parameter and promising therapeutic target for gastric cancer.

scholarly journals Polymorphisms of the DNA Methyltransferase 1 Gene Predict Survival of Gastric Cancer Patients Receiving Tumorectomy

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Zhifang Jia ◽  
Xing Wu ◽  
Donghui Cao ◽  
Chuan Wang ◽  
Lili You ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Dna Methyltransferase ◽  
Cox Regression ◽  
Methylation Status ◽  
Dna Methyltransferase 1 ◽  
Cox Regression Analysis ◽  
Independent Prognostic Marker ◽  
Gastric Cancer Patients ◽  
Methyltransferase 1

DNA methyltransferase 1 (DNMT1) plays a pivotal role in maintaining DNA methylation status. Polymorphisms ofDNMT1may modify the role of DNMT1 in prognosis of gastric cancer (GC). Our aim was to test whether polymorphisms ofDNMT1gene were associated with overall survival of GC. Four hundred and forty-seven GC patients who underwent radical tumorectomy were enrolled in the study. Five tagging SNPs (rs10420321, rs16999593, rs2228612, rs2228611, and rs2288349) of theDNMT1gene were genotyped by TaqMan assays. Kaplan-Meier survival plots and Cox proportional hazard regression were used to analyze the associations between SNPs ofDNMT1and survival of GC. Patients carrying rs2228611 GA/AA genotype tended to live longer than those bearing the GG genotype (HR 0.68, 95% CI: 0.51–0.91,P=0.007). Further multivariate Cox regression analysis showed that rs2228611 was an independent prognostic factor (GA/AA versus GG: OR 0.67, 95% CI 0.49–0.91,P=0.010). Nevertheless, other SNPs did not show any significant associations with survival of GC. Polymorphisms of theDNMT1gene may affect overall survival of GC. The SNP rs2228611 has the potentiality to serve as an independent prognostic marker for GC patients.

Methylated TIMP-3 DNA in Body Fluids Is an Independent Prognostic Factor for Gastric Cancer

2014 ◽  
Vol 138 (11) ◽  
pp. 1466-1473 ◽  
Author(s):  
Jiang-Liu Yu ◽  
Ping Lv ◽  
Jing Han ◽  
Xin Zhu ◽  
Lian-Lian Hong ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cox Regression ◽  
Characteristic Curve ◽  
Disease Free Survival ◽  
Body Fluids ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Serum Samples ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Disease Free

Context Fluid methylated DNA may be a suitable biomarker for cancer patients. Objective To investigate whether circulating methylated tissue inhibitor of metalloproteinase 3 (TIMP-3) DNA in body fluids is a useful prognostic biomarker in gastric cancer (GC). Design TIMP-3 methylation was detected by real-time methylation-specific polymerase chain reaction in tumor tissues, paired preoperative peritoneal washes (PPWs), and paired serum samples from 92 GC patients. Results The frequency of TIMP-3 methylation was significantly elevated in GC tissues (63.04%; 58 of 92) compared with that in paired adjacent normal tissue (4.3%; 4 of 92) (P &lt; .001). TIMP-3 methylation correlated closely with peritoneal metastasis and TNM stage (all P &lt; .001). The frequency of TIMP-3 methylation in preoperative peritoneal washes and serum samples was 53.3% (49 of 92) and 58.7% (54 of 92), respectively. The Aζ values of the receiver operator characteristic curve for methylated TIMP-3 were 0.966 and 0.922 for serum and preoperative peritoneal washes, respectively, compared with those in GC tissues. The patients with elevated methylated TIMP-3 levels in body fluids had poorer disease-free survival rates than those without (all P &lt; .001). Cox regression analysis showed that detection of methylated TIMP-3 DNA in body fluids was an independent risk factor for GC patients, with a remarkable decrease in disease-free survival 30 months after surgical resection of the gastric tumor. Conclusion Presence of methylated TIMP-3 DNA in body fluids is a useful biomarker for predicting the progression and prognosis of GC patients.

scholarly journals BIOM-31. PROGNOSTIC VALUE OF MGMT METHYLATION IN IDH MUTANT GLIOMAS

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii8-ii8
Author(s):  
Keng Lam ◽  
Blaine Eldred ◽  
Bryan Kevan ◽  
Matthew Ji ◽  
Jerry Lou ◽  
...  
Keyword(s):  
Los Angeles ◽  
Promoter Methylation ◽  
Prognostic Value ◽  
Cox Regression ◽  
Methylation Status ◽  
Hazard Ratio ◽  
Mgmt Promoter Methylation ◽  
Mgmt Methylation ◽  
Cox Regression Analysis ◽  
Mgmt Promoter

Abstract BACKGROUND Patients with isocitrate dehydrogenase (IDH) mutant gliomas have been associated with longer survival time than those with IDH wildtype. Previous studies have also shown the predictive value of O-6-methylguanine-DNA methyltransferase (MGMT) promoter methylation for glioblastoma. However, little is known in the prognostic value of MGMT methylation status for IDH mutant gliomas. METHODS We retrospectively identified IDH mutant gliomas patients from University of California Los Angeles and Kaiser Permanente Los Angeles that had been tested for MGMT methylation status. We performed Kaplan-Meier and Cox regression analyses of overall survival (OS) to compare the MGMT methylated versus MGMT unmethylated patients. RESULTS We identified a total of 375 IDH mutant gliomas with MGMT testing. Subgroups include 52 glioblastoma, 191 astrocytoma, and 132 oligodendroglioma. The median OS for all MGMT methylated patients was 20.0 years and for unmethylated patients 14.3 years (log-rank P=0.008). Cox regression analysis also confirmed patients with MGMT methylated to have better survival than those with MGMT unmethylated (hazard ratio of 0.47, P= 0.005). During subgroup analysis, MGMT methylated glioblastoma patients have a median OS of 13.7 years compared to MGMT unmethylated patients 3.2 years (log-rank P=0.004) with a hazard ratio of 0.14 (P=0.005). However, we see no difference yet for astrocytoma (hazard ratio of 1.09, P= 0.81) and oligodendrogliomas (hazard ratio of 0.36, P= 0.193), possibly as a result of immature survival data. CONCLUSIONS MGMT promoter methylation is associated with better outcomes in IDH mutant glioblastoma patients. Progression free survival will be analyzed to determine predictive benefit of MGMT methylation for other glioma subtypes.

scholarly journals ACTR-37. ASSOCIATION BETWEEN MGMT PROMOTER METHYLATION SCORE AND SURVIVAL IN PATIENTS WITH GLIOBLASTOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi21-vi21
Author(s):  
Carlos Romo ◽  
Pavan Shah ◽  
Yuqing Sun ◽  
Xiaobu Ye ◽  
Stuart Grossman
Keyword(s):  
Promoter Methylation ◽  
Cox Regression ◽  
Methylation Status ◽  
Positive Association ◽  
Primary Objective ◽  
Mgmt Promoter Methylation ◽  
Specific Pcr ◽  
Mgmt Promoter ◽  
Methylation Score ◽  
Group 2

Abstract BACKGROUND MGMT promoter methylation is associated with longer survival in patients with high-grade gliomas who receive alkylating therapy. Methylation status is commonly determined by methylation-specific PCR and results are reported in two forms: a dichotomization of “present” or “not present,” and as a methylation score (MGMT/beta-actinx1000). The primary objective of this study is to determine the association between the degree of methylation and overall survival (OS) in newly diagnosed patients with glioblastoma. METHODS A retrospective IRB-approved study was conducted of 684 patients treated at Johns Hopkins from 2007–2015. Adults with a histologically confirmed glioblastoma treated with standard therapy were included in the analysis. OS was estimated from the date of diagnosis to time of death or last follow up using the Kaplan–Meier method. Cox regression model was used to assess possible positive association between MGMT score and OS. For purposes of this analysis IDH1-mutated patients were excluded. RESULTS In 100 evaluable patients, median age at diagnosis was 56 years [45–77]. Fifty-two patients were MGMT promoter methylated (score ≥2.00) and 48 were unmethylated. The median OS was 31 months in the methylated patients and 15 months in the unmethylated (p=0.0001). Methylated patients had MGMT scores ranging from 2.53-1278. The methylated scores were classified into 3 groups; #1: 0-25th percentile, #2: 25-75th percentiles, and #3: >75th percentile. mOS was: 30.8 months for group 1 (n=13); 34.8 months for group 2 (n=27); and 20.9 months for group 3 (n=12) (p=0.19). Difference in mOS between groups 1 and 3 was not statistically significant (HR 0.819 [95% CI, 0.3–2.2], p=0.69). DISCUSSION The prognostic value of MGMT promoter methylation in patients with glioblastoma was replicated in our study sample. The degree of methylation reported as a score on routine testing does not appear to be directly related to OS in this patient population.

scholarly journals TINCR expression is associated with unfavorable prognosis in patients with hepatocellular carcinoma

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Feng Tian ◽  
Jian Xu ◽  
Fangxi Xue ◽  
Encui Guan ◽  
Xiaoguang Xu
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Prognostic Indicator ◽  
Clinicopathological Characteristics ◽  
Cox Regression Analysis ◽  
Functional Roles ◽  
Kaplan Meier ◽  
Promising Target ◽  
Differentiation Status

Emerging evidence are accumulating that long noncoding RNAs (lncRNAs) have recently been identified to participate in various cellular processes. Terminal differentiation induced ncRNA (TINCR) is a newly identified lncRNA with its functional roles not fully elucidated in human malignancy. The current study aims to identify the clinical significance of TINCR in prognosis and malignant progression of hepatocellular carcinoma (HCC). TINCR expression in HCC specimens at various stages of tumorigenesis were measured by quantitative real-time RT PCR (qRT-PCR). The matched para-carcinoma tissues were used as controls. The associations of TINCR with clinicopathological characteristics, disease-free survival (DFS) and overall survival (OS) of patients were further evaluated. Results revealed that high TINCR expression was significantly correlated with tumor size (P=0.005), tumor differentiation status (P=0.017), TNM stage (P=0.010), and vascular invasion (P=0.004). Moreover, Kaplan–Meier analysis demonstrated that TINCR was correlated to both DFS and OS in HCC cohorts. Patients with high TINCR expression tended to have worse prognosis. Multivariate Cox regression analysis indicated that TINCR was an independent poor prognostic indicator for DFS (HR =1.32, 95% CI: 1.00–1.57, P=0.000) and OS (HR =1.57, 95% CI: 1.30–1.86, P=0.004) in HCC. TINCR was demonstrated as a direct target of miR-137 and miR-133a, and was suppressed by miR-137/miR-133a. These results provide the first evidence that the expression of TINCR in HCC may play an oncogenic role in HCC differentiation, invasion, and metastasis. miR-137/miR-133a-TINCR pathway may serve as a promising target for tumor recurrence and prognosis of patients with HCC.

Expression of carbohydrate antigen sialyl Le(a): a new functional prognostic factor in gastric cancer.

1997 ◽  
Vol 15 (2) ◽  
pp. 816-825 ◽  
Author(s):  
S Nakamori ◽  
H Furukawa ◽  
M Hiratsuka ◽  
T Iwanaga ◽  
S Imaoka ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prognostic Factor ◽  
Cox Regression ◽  
Intensive Therapy ◽  
Antigen Expression ◽  
Prognostic Indicator ◽  
Depth Of Invasion ◽  
Altered Expression ◽  
Cox Regression Analysis ◽  
Clinicopathologic Factors

PURPOSE The prognostic value of the altered expression of carbohydrate antigens sialyl Le(a) (sLe(a)) and sialyl Le(x) (sLe(x)), which have been implicated as functional ligands in heterotypic-cell-adhesion systems in the multistep process of tumor metastasis, were evaluated. PATIENTS AND METHODS The level of expression of sLe(a) and sLe(x) antigens was examined immunohistochemically in paraffin-embedded tumor samples from 137 patients who underwent resection for gastric cancer. Correlation between the antigens' expression, various established clinicopathologic factors, and prognosis were studied by univariate and multivariate analysis. RESULTS Tumors that were positive for the sLe(a) antigen were significantly more likely to be large (P = .035), to be localized at the proximal third of the stomach (P = .018), to have an infiltrate appearance (P = .013), to have an invasive mode both in depth of invasion (P = .028) and in lymphatic invasion (P = .002), and to be classified as late stage (P = .011) than those that were negative for sLe(a), whereas the sLe(x) antigen status was not correlated with any clinicopathologic factors. The overall survival of patients with an sLe(a)-antigen-positive tumor was significantly poorer than that of those with an sLe(a)-antigen-negative tumor (P = .0001). Survival within each pathologic stage differed also (stage I, P = .030; stage II, P = .046; stage III, P = .026, respectively). A Cox regression analysis with multiple covariates showed that positive sLe(a) antigen status was an independent prognostic factor for a worse outcome in patients with gastric cancer. According to the mode of recurrence, increased sLe(a) antigen expression significantly affected both peritoneal dissemination and liver metastasis. CONCLUSION Increased expression of the sLe(a) antigen may serve as a potent prognostic indicator for recurrence in patients with gastric cancer. Careful follow-up and intensive therapy are required for patients with an sLe(a)-antigen-positive gastric cancer.

scholarly journals Diagnostic and prognostic value of the methylation status of secreted frizzled-related protein 2 in colorectal cancer

2011 ◽  
Vol 34 (1) ◽  
pp. 88 ◽  
Author(s):  
Dong Tang ◽  
Jun Liu ◽  
Dao-rong Wang ◽  
Hai-feng Yu ◽  
Yong-kun Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Promoter Methylation ◽  
Cox Regression ◽  
Precancerous Lesions ◽  
Methylation Status ◽  
Prognostic Significance ◽  
Related Protein ◽  
Serum Samples ◽  
Cox Regression Analysis

Purpose: The aim of this study was to investigate the diagnostic and prognostic significance of the methylation status of secreted frizzled-related protein 2 (SFRP2) in colorectal cancer (CRC). Methods: Methylation-specific PCR assay was performed to analyze SFRP2 promoter methylation in solid tissue, stool and serum samples collected from 169 CRC patients, 63 patients with advanced adenomas, 46 patients with non-adenomatous polyps and 30 normal healthy controls. Results: Methylated SFRP2 was frequently detected in CRC tissues and precancerous lesions. The sensitivity of SFRP2 methylation levels in tissue, fecal and serum DNA for the detection of CRC was similar, ranging from 66.9 to 88.2%; however, serum SFRP2 methylation levels showed a markedly higher specificity in discriminating CRCs from benign adenomas than those of SFRP2 methylation levels in tumor and fecal DNA. Moreover, serum SFRP2 methylation was significantly associated with poor differentiation grade (P=0.019), serosal/subserosal invasion (P < 0.001), lymph node metastasis status (P < 0.001) and TNM stage (P < 0.001) of CRC. CRC patients with SFRP2 hypermethylation in tumor, stool and serum samples had a significantly shorter overall survival than those negative for SFRP2 methylation (P=0.0216, 0.0219, and 0.0255, respectively). Multivariate Cox regression analysis revealed that SFRP2 promoter methylation in tumor samples was an independent prognostic factor for overall survival. Conclusion: Our data suggest that serum SFRP2 methylation status represents a promising, non-invasive marker for CRC detection and staging. Hypermethylated SFRP2 may have prognostic relevance in patients with CRC.

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