Dataset Information

Association of sirtuins with clinicopathological parameters and overall survival in gastric cancer.

ABSTRACT: To evaluate the associations of sirtuins (SIRT1-7) with clinicopathological parameters in gastric cancer, sirtuins expression profile in NCBI GEO datasets, GSE62254 and GSE15459, was integrated and analyzed. The results suggested that SIRT4, SIRT6, and SIRT7 were associated with Lauren classification and SIRT3-5 were associated with pStage in gastric cancer. Then an online database derived from 1,065 gastric cancer cases, Kaplan-Meier plotter, was used to explore the associations of the mRNA levels of sirtuins with overall survival in gastric cancer. Survival curves generated from Kaplan-Meier plotter suggested that high expression of SIRT1 mRNA was favorable for overall survival in gastric cancer (SIRT1: HR = 0.64, 95% CI = 0.54-0.76, P = 2.2E-07), high expressions of SIRT2-4 and SIRT6-7 were poor for overall survival (SIRT2: HR = 2.31, 95% CI = 1.87-2.87, P = 3.6E-15; SIRT3: HR = 1.99, 95% CI = 1.62-2.45, P = 2.6E-11; SIRT4: HR = 1.41, 95% CI = 1.19-1.68, P = 6.6E-05; SIRT6: HR = 2.02, 95% CI = 1.66-2.47, P = 1.7E-12; SIRT7: HR = 1.96, 95% CI = 1.63-2.35, P = 2.7E-13), whereas no significant association existed between SIRT5 mRNA expression and overall survival. Further analyses stratified by gender, stages, Lauren classification, differentiation, treatment, and HER2 status were also performed. In summary, high SIRT1 mRNA level was associated with better overall survival, SIRT2-4 and 6-7 were associated with poor overall survival, whereas SIRT5 did not show significant association with overall survival in gastric cancer.

SUBMITTER: Shen X

PROVIDER: S-EPMC5650347 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Association of sirtuins with clinicopathological parameters and overall survival in gastric cancer.

Shen Xiaobing X Li Pengfei P Xu Yuchao Y Chen Xiaowei X Sun Haixiang H Zhao Ying Y Liu Mengqi M Zhang Wenwen W

Oncotarget 20170908 43

To evaluate the associations of sirtuins (SIRT1-7) with clinicopathological parameters in gastric cancer, sirtuins expression profile in NCBI GEO datasets, GSE62254 and GSE15459, was integrated and analyzed. The results suggested that SIRT4, SIRT6, and SIRT7 were associated with Lauren classification and SIRT3-5 were associated with pStage in gastric cancer. Then an online database derived from 1,065 gastric cancer cases, Kaplan-Meier plotter, was used to explore the associations of the mRNA lev ...[more]

PMID: 29088792

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Project description:ObjectivesGastric neuroendocrine carcinoma (GNEC) is a class of rare histological subtypes in gastric cancer (GC). This retrospective case-control study aimed to explore the clinicopathological features and overall survival (OS) of patients with GNEC.MethodsA large population of GNEC and intestinal-type GC (IGC) patients were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The 1:1 propensity score matching (PSM) analysis was initiated to adjust the confounders between GNEC and IGC cohorts. Kaplan-Meier (KM) plots with log-rank tests were used to compare the survival differences in GNEC versus IGC. Additionally, Cox proportional hazard regression models were adopted to characterize the prognostic factors relevant to OS of the GNEC patients.ResultsAn entity of 4596 patients were collected, including 3943 (85.8%) IGC patients and 653 (14.2%) GNEC patients. The PSM analysis well-balanced all confounders in GNEC versus IGC (all P > .05). The KM plots showed that GNEC had significantly superior OS to IGC both before and after PSM analysis. Before PSM, the median OS was 52 (33.6-70.4) months in GNEC versus 32 (29.3-34.7) months in IGC (P = .0015). After PSM, the median OS was 26 (18.3-33.7) months in GNEC versus 21 (17.7-24.3) months in IGC (P = .0039). Stratified analysis indicated that GNEC had superior survivals to IGC in early stage patients and those who received surgery. In Cox regression analysis, age ≥ 60, tumor size > 50 mm, stage II-IV, T2, and N3 were independent risk factors for the GNEC patients (hazard ratio [HR]>1, P < .05). By contrast, year 2010 to 2015, female, and surgery were independent protective factors for these patients (HR < 1, P < .05).ConclusionsGNEC has unique clinicopathological features quite different from IGC and may have a superior survival to IGC in early stage patients. The prognostic factors identified here may assist the clinicians to more individually treat these patients.

Project description:IntroductionThe Cancer Genome Atlas (TCGA) project and Asian Cancer Research Group (ACRG) recently categorized gastric cancer into molecular subtypes. Nevertheless, these classification systems require high cost and sophisticated molecular technologies, preventing their widespread use in the clinic. This study is aimed to generating molecular subtypes of gastric cancer using techniques available in routine diagnostic practice in a series of Moroccan gastric cancer patients. In addition, we assessed the associations between molecular subtypes, clinicopathological features, and prognosis.MethodsNinety-seven gastric cancer cases were classified according to TCGA, ACRG, and integrated classifications using a panel of four molecular markers (EBV, MSI, E-cadherin, and p53). HER2 status and PD-L1 expression were also evaluated. These markers were analyzed using immunohistochemistry (E-cadherin, p53, HER2, and PD-L1), in situ hybridization (EBV and HER2 equivocal cases), and multiplex PCR (MSI).ResultsOur results showed that the subtypes presented distinct clinicopathological features and prognosis. EBV-positive gastric cancers were found exclusively in male patients. The GS (TCGA classification), MSS/EMT (ACRG classification), and E-cadherin aberrant subtype (integrated classification) presented the Lauren diffuse histology enrichment and tended to be diagnosed at a younger age. The MSI subtype was associated with a better overall survival across all classifications (TCGA, ACRG, and integrated classification). The worst prognosis was observed in the EBV subtype (TCGA and integrated classification) and MSS/EMT subtype (ACRG classification). Discussion/Conclusion. We reported a reproducible and affordable gastric cancer subtyping algorithms that can reproduce the recently recognized TCGA, ACRG, and integrated gastric cancer classifications, using techniques available in routine diagnosis. These simplified classifications can be employed not only for molecular classification but also in predicting the prognosis of gastric cancer patients.

Project description:BackgroundCopines-1 (CPNE1) is a soluble membrane-binding protein that includes two tandem C2 domains at the N-terminus and a C terminal A domain. Importantly, it is associated with the prognosis of various tumors, but there are only a few studies regarding the role of CPNE1 in gastric cancer (GC). This study aimed to explore the clinicopathological significance and prognostic potential of CPNE1 expression in GC.MethodsData from the TIMER2.0 and UALCAN were analyzed to assess CPNE1 mRNA levels in GC. The prognostic role of CPNE1 mRNA was examined via the Kaplan-Meier plotter. CPNE1 protein expression in tumor tissues was analyzed via immunohistochemistry of clinical samples from 99 GC patients. The relationship of CPNE1 expression with clinicopathological parameters and overall survival (OS) was evaluated using Cox proportional hazards regression models and Kaplan-Meier survival curves.ResultsCopines-1 mRNA levels were higher in GC tissues than in adjacent normal tissue (ANT) (p < 0.05). Further, high CPNE1 mRNA expression indicated poor OS (p = 9.4 e-10) and was significantly associated with first progression (FP) (p = 1.6 e-06) and post-progression survival (PPS) (p = 1.5 e-12). In addition, CPNE1 protein expression was higher in GC tissues than in ANT (p < 0.0001). Moreover, CPNE1 high expression was significantly related to advanced tumor-node-metastasis (TNM) stage (p = 0.004), lymph node metastasis (p = 0.003), and vascular invasion (p = 0.001). Kaplan-Meier analysis showed that GC patients with high expression CPNE1 group had worse OS than low expression group (p = 0.003). Univariate analysis showed that age (hazard ratio [HR] = 1.992; 95% confidence interval [CI], 1.009-3.934; p = 0.047), advanced TNM stage (HR = 4.941; 95% CI, 2.052-11.897; p = 0.000), tumor invasion (HR = 3.472; 95% CI, 1.349-8.937; p = 0.010), lymph node metastasis (HR = 8.846; 95% CI, 2.708-28.897; p = 0.000), vascular invasion (HR = 3.237; 95% CI, 1.521-6.891; p = 0.002), nervous invasion (HR = 2.324; 95% CI, 1.205-4.479; p = 0.012), and CPNE1 expression (HR = 3.464; 95% CI, 1.440-8.334; p = 0.006) were correlated with OS. In the multivariate analysis, age (HR = 2.514; 95% CI, 1.264-4.999; p = 0.009), lymph node metastasis (HR = 8.441; 95% CI, 2.553-27.906; p < 0.05), and CPNE1 expression (HR = 2.549; 95% CI, 1.051-6.186; p = 0.039) were significant prognostic predictors for GC.ConclusionsCopines-1 overexpression in GC is significantly associated with poor prognosis. Thus, CPNE1 levels may serve as a prognostic biomarker in GC patients.

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Dataset Information

Association of sirtuins with clinicopathological parameters and overall survival in gastric cancer.

Publications

Association of sirtuins with clinicopathological parameters and overall survival in gastric cancer.

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