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The discovery and validation of ten-gene prognostic classifier in gastric cancer by whole genome expression profiling

ABSTRACT: The aim of this study is to identify and verify a prognosis set that is able to distinguish patient overall survival status based on whole genome expression profiling. Using Illumina HumanWG-6 beadarray, we analyzed the expression of 47,296 transcripts in two groups of gastric cancer patients who all underwent surgical resection. Thirty-nine of 46 samples in group one were used as a training set to discover candidates for overall survival prediction by using semi-supervised method, resulting in a panel of 10 genes as prognosis markers. This 10-marker set classified each case into a low or a high risk group with significantly different survival times (P = 0.000047) and maintained independent prognostic value in multivariate analysis. These 10 candidates were then verified in a fully independent validation set comprising 33 samples (P = 0.0009). Furthermore, the prognosis was consistent with the classical TNM staging system, and showed even better prediction. Interestingly, six of ten survival markers are ribosomal proteins, suggesting a possible association between deregulation of ribosome-related expression and poor prognosis. In conclusion, by whole genome expression profiling, 10 markers, including 6 ribosomal proteins, for overall survival prognosis of gastric cancer were found and validated, and which may be parallelly used with the TNM system.

ORGANISM(S): Homo sapiens

PROVIDER: GSE21983 | GEO | 2011/07/13

SECONDARY ACCESSION(S): PRJNA127195

REPOSITORIES: GEO

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Similar Datasets

The discovery and validation of ten-gene prognostic classifier in gastric cancer by whole genome expression profiling

Project description:The aim of this study is to identify and verify a prognosis set that is able to distinguish patient overall survival status based on whole genome expression profiling. Using Illumina HumanWG-6 beadarray, we analyzed the expression of 47,296 transcripts in two groups of gastric cancer patients who all underwent surgical resection. Thirty-nine of 46 samples in group one were used as a training set to discover candidates for overall survival prediction by using semi-supervised method, resulting in a panel of 10 genes as prognosis markers. This 10-marker set classified each case into a low or a high risk group with significantly different survival times (P = 0.000047) and maintained independent prognostic value in multivariate analysis. These 10 candidates were then verified in a fully independent validation set comprising 33 samples (P = 0.0009). Furthermore, the prognosis was consistent with the classical TNM staging system, and showed even better prediction. Interestingly, six of ten survival markers are ribosomal proteins, suggesting a possible association between deregulation of ribosome-related expression and poor prognosis. In conclusion, by whole genome expression profiling, 10 markers, including 6 ribosomal proteins, for overall survival prognosis of gastric cancer were found and validated, and which may be parallelly used with the TNM system. We investigated the transcriptome profiles of gastric cancer patients with different prognosis. Thirty-nine patients from first batch samples were used to discover prognostic markers and another 33 samples from batch two were used for validation.

2011-07-12 | E-GEOD-21983 | biostudies-arrayexpress

Expression data of Human Gastric Adenocarcinoma

Project description:Anatomical staging is a critical, although imperfect, instrument to assess gastric cancer prognosis and define indication for surgery and adjuvant therapy. Despite recent advances, treatment results, as a whole, remain less than satisfactory. Thus, biomarkers are sorely needed to improve risk categorization and define new molecular targets for therapy. We used microarrays to identify genes differentially expressed according to prognosis of the patients. A cohort of 15 patients was prospectively identified with a histological diagnosis of gastric adenocarcinoma, submitted to surgery with curative intent. Two prognostic patient groups were defined, according to overall survival (short x long), with a 24 month cut-off. These groups were matched by known prognostic factors: TNM staging, histological subtype (intestinal/diffuse) and gender.

2012-09-01 | E-GEOD-38749 | biostudies-arrayexpress

Gene expression profile prospectively predicts peritoneal relapse after curative surgery of gastric cancer

Project description:Purpose: Our study aimed to disclose the specific gene expression profile representing peritoneal relapses inherent in primary gastric cancers and to identify patients at high risk of peritoneal relapse in a prospective study on the basis of the molecular prediction. Experimental Design: RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly we constructed molecular prediction system and validated the robustness and prognostic validity of the analysis by 500 times multiple random sampling in 56 retrospective set consisting of 38 relapse free and 18 peritoneal relapse patients. Secondly we applied this prediction to 85 prospective set to assess the predictive accuracy and prognostic validity. Results: In retrospective phase, 500 times multiple random sampling analysis yielded 68% predictive accuracy in average and 22 gene expression profile associated with peritoneal relapse was identified. This prediction could identify significantly poor prognostic patients. In prospective phase, the molecular prediction yielded 76.9% overall accuracy. KaplanâMeier analysis with peritoneal relapse free survival showed a significant difference between âgood signature groupâ and âpoor signature groupâ (Log-rank p=0.0017). Multivariate analysis by Cox regression hazards model revealed that the molecular prediction was the only independent peritoneal relapse prognostic factor. Conclusions: Gene expression profile inherent in primary gastric cancer tissues can be useful to predict peritoneal relapse prospectively after curative surgery and individualize postoperative management to improve the prognosis of advanced gastric cancers. Of 141 samples, 56 represented the retrospective phase and 85 represented the prospective phase.

2010-05-23 | E-GEOD-15081 | biostudies-arrayexpress

Gene expression profile prospectively predicts peritoneal relapse after curative surgery of gastric cancer

Project description:Purpose: Our study aimed to disclose the specific gene expression profile representing peritoneal relapses inherent in primary gastric cancers and to identify patients at high risk of peritoneal relapse in a prospective study on the basis of the molecular prediction. Experimental Design: RNA samples from 141 primary gastric cancer tissues after curative surgery were profiled using oligonucleotide microarrays covering 30,000 human probes. Firstly we constructed molecular prediction system and validated the robustness and prognostic validity of the analysis by 500 times multiple random sampling in 56 retrospective set consisting of 38 relapse free and 18 peritoneal relapse patients. Secondly we applied this prediction to 85 prospective set to assess the predictive accuracy and prognostic validity. Results: In retrospective phase, 500 times multiple random sampling analysis yielded 68% predictive accuracy in average and 22 gene expression profile associated with peritoneal relapse was identified. This prediction could identify significantly poor prognostic patients. In prospective phase, the molecular prediction yielded 76.9% overall accuracy. Kaplan–Meier analysis with peritoneal relapse free survival showed a significant difference between ‘good signature group’ and ‘poor signature group’ (Log-rank p=0.0017). Multivariate analysis by Cox regression hazards model revealed that the molecular prediction was the only independent peritoneal relapse prognostic factor. Conclusions: Gene expression profile inherent in primary gastric cancer tissues can be useful to predict peritoneal relapse prospectively after curative surgery and individualize postoperative management to improve the prognosis of advanced gastric cancers.

2009-03-04 | GSE15081 | GEO

Seven-lncRNA signature in esophageal squamous cell carcinoma

Project description:A seven-lncRNA signature was identified in the training set, which is significantly associated with overall survival (OS) (Hazard Ratio [HR]: 3.535, 95% confidence interval [CI]: 2.113-5.915, P < 0.001) and disease-free survival (DFS) (Hazard Ratio [HR]: 2.413, 95% confidence interval [CI]: 1.573-3.703, P < 0.001). Patients in high-risk group have shorter overall survival (HR: 3.555, 95% CI: 2.195-5.757, p < 0.001) and disease-free survival (HR: 2.537, 95% CI: 1.646-3.909, p < 0.001) in the training set, and we found the same conclusion in the independent set for OS (HR 2.665, p < 0.001) and DFS (HR 2.360, p = 0.001). Combination of the signature and TNM staging system was more powerful than TNM staging system alone in predicting outcomes in both the training set (AUC: 0.772 vs 0.681, p = 0.002) and in the independent set (AUC: 0.772 vs 0.660, p = 0.003).

2020-02-10 | GSE92986 | GEO

Development of a two-circular RNA panel as potential prognostic biomarker for gastric cancer

Project description:Background: Circular RNAs (circRNAs) have attracted increasing attention in recent years for their potential application as disease biomarkers due to their high abundance and stability. In this study, we attempted to screen circRNAs that can be used to predict postoperative recurrence and survival in patients with gastric cancer (GC). Methods: High-throughput RNA sequencing was used to identify differentially expressed circRNAs in GC patients with different prognoses. The expression level of circRNAs in the training set (n=136) and validation set (n=167) was detected by quantitative real-time PCR (qRT-PCR). Kaplan–Meier estimator, receiver operating characteristic (ROC) curve and cox regression analysis were used to evaluate the prognostic value of circRNAs on recurrence-free survival (RFS) and overall survival (OS) in GC patients. CeRNA network prediction, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for the circRNAs with prognostic significance. Results: A total of 259 differentially expressed circRNAs were identified in GC patients with different RFS. We found two circRNAs (hsa_circ_0005092 and hsa_circ_0002647) that highly expressed in GC patients with good prognoses, and subsequently established a predictive model for postoperative recurrence and prognosis evaluation, named circPanel. Patients with circPanellow might have shorter recurrence-free survival (RFS) and overall survival (OS). We also performed circRNA-miRNA-mRNA network prediction and functional analysis for hsa_circ_0005092 and hsa_circ_0002647. Conclusions: CircPanel has the potential to be a prognostic biomarker in GC patients with greater accuracy than a single circRNA and certain traditional tumor markers (e.g., CEA, CA19-9 and CA724).

2021-08-12 | GSE181769 | GEO

ALDH2, CCNE1 and SMAD3 are Potential Prognostic Markers for Upper Tract Urothelial Carcinoma Revealed by Massively Parallel Sequencing.

Project description:Purpose: upper tract urothelial carcinoma (UTUC) is the predominant subtype of the renal pelvis carcinoma but current knowledge about the molecular properties and prognostic markers is sparse. In this study, we examined the genome-wide mRNA expression spectrum of UTUC aiming to characterize the molecular basis of this cancer, and identify potential prognostic markers and thus facilitate the clinical practices. Experimental Design: we compared the whole mRNA expression spectrum of cancer and matched normal tissues in 10 patients with UTUC using massively parallel sequencing, thereafter the protein levels and prognostic roles of ALDH2, CCNE1 and SMAD3 were evaluated under an independent validation set comprising of 104 patients. Results: mRNA down-regulation of ALDH2 and up-regulation of SMAD3 and CCNE1 in UTUC were revealed by expression profiling. And low protein expression of ALDH2 was associated with an adverse outcome for patients (p < 0.0001). Whereas high CCNE1 and SMAD3 were associated with adverse clinical outcome (p < 0.0001). And multivariate analysis revealed that all these three molecular markers were independent prognostic predictors. Besides, compared to the pathological TNM classification, All ALDH2, CCNE1 and SMAD3 were more competent in identifying patient subgroup with high mortality risk, and the molecular markers were able to predict the survival difference in the patients of T2 and T3 subgroup (p < 0.001), which could not be achieved by TNM staging. Conclusions: This is the ﬁrst prospective study that characterizes genome-wide mRNA expression profile of UTUC. We revealed the prognostic significance of ALDH2, CCNE1 and SMAD3, and these molecular marker were more robust than TNM system in clinical outcome prediction.

2015-01-01 | GSE47702 | GEO

MiRNA Expression Profile Study Reveals a Prognostic Signature for Esophageal Squamous Cell Carcinoma

Project description:Esophageal cancer is a highly malignant and prevalent cancer worldwide. Current TNM staging system is insufficient for prognosis of esophagus squamous cell carcinoma (ESCC) patients. The aim of this study is to evaluate miRNA expression profile of ESCC and identify a miRNA signature which robustly predict the survival of ESCC patients. MiRNA expression profiles of paired frozen tissues from 119 ESCC patients were assessed by microarray. After normalization of microarray data, the patients were randomly divided into a training set (n=60) and a test set (n=59). From the training set, we identified a four-miRNA prognostic signature (including hsa-miR-218-5p, hsa-miR-142-3p, hsa-miR-150-5p, and hsa-miR-205-5p) using random forest supervised classification algorithm and nearest shrunken centroid algorithm. This signature distinguished the patients into high-risk or low-risk groups whose overall survival differed significantly (5-year survival 7.4% vs. 66.7%, p<0.001). Prognostic value of this signature was validated in the test set (5-year survival 18.8% vs. 46.5%, p=0.025) and further in an independent cohort of 58 patients assessed by a different platform (5-year survival 11.4% vs. 56.7%, p=0.003). Furthermore, multivariable Cox regression analysis revealed that this signature is an independent prognostic factor for ESCC patients. Moreover, stratified analysis showed that this signature was able to predict survival within TNM stages. The expression level of the four miRNAs measured by microarray was verified by qRT-PCR and showed high level of positive correlation (Pearson correlation coefficient>0.75, p<0.001 for all). Our results suggest that the four-miRNA signature can serve as a reliable biomarker to predict the survival of ESCC patients. the miRNA expression profiles of cancer and adjacent normal tissues form 119 ESCC patients were used to identify a miRNA signature that can perdict the survival of ESCC patients.

2014-08-01 | E-GEOD-43732 | biostudies-arrayexpress

Genetic changes in gastric adenoca tumors

Project description:The genetic changes in gastric adenocarcinoma are extremely complex and reliable tumor markers have not yet been identified. There are also remarkable geographical differences in the distribution of this disease. Our aim was to identify the most differentially regulated genes in 20 gastric adenocarcinomas from a Norwegian selection, compared to matched normal mucosa, and have related our findings to prognosis, survival and chronic Helicobacter pylori infection

2013-07-01 | E-MTAB-1440 | biostudies-arrayexpress

MiRNA Expression Profile Study Reveals a Prognostic Signature for Esophageal Squamous Cell Carcinoma

2014-08-01 | GSE43732 | GEO

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