Dataset Information

Identification of hsa-miR-335 as a prognostic signature in gastric cancer.

ABSTRACT: BACKGROUND: Gastric cancer (GC) is one of the most common malignancy and primary cause of death in Chinese cancer patients. Recurrence is a major factor leading to treatment failure and low level of 5-year survival rate in GC patients following surgical resection. Therefore, identification of biomarkers with potential in predicting recurrence risk is the key problem of the prognosis in GC patients. PATIENTS AND METHODS: A total of 74 GC patients were selected for systematic analysis, consisting of 31 patients with recurrence and 43 patients without recurrence. Firstly, miRNAs microarray and bioinformatics methods were used to characterize differential expressed miRNAs from primary tumor samples. Following, we used a ROC method to select signature with best sensitivity and specificity. Finally, we validated the signature in GC samples (frozen fresh and blood samples) using quantitative PCR. RESULTS: We have identified 12 differential miRNAs including 7 up-regulated and 5 down-regulated miRNAs in recurrence group. Using ROC method, we further ascertained hsa-miR-335 as a signature to recognize recurrence and non-recurrence cases in the training samples. Moreover, we validated this signature using quantitative PCR method in 64 test samples with consistent result with training set. A high frequency recurrence and poor survival were observed in GC cases with high level of hsa-miR-335 (P<0.001). In addition, we evaluated that hsa-miR-335 were involved in regulating target genes in several oncogenic signal-pathways, such as p53, MAPK, TGF-?, Wnt, ERbB, mTOR, Toll-like receptor and focal adhesion. CONCLUSION: Our results indicate that the hsa-miR-335 has the potential to recognize the recurrence risk and relate to the prognosis of GC patients.

SUBMITTER: Yan Z

PROVIDER: S-EPMC3388997 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Identification of hsa-miR-335 as a prognostic signature in gastric cancer.

Yan Zhi Z Xiong Yimin Y Xu Weitian W Gao Juan J Cheng Yi Y Wang Zhigang Z Chen Fang F Zheng Guorong G

PloS one 20120703 7

<h4>Background</h4>Gastric cancer (GC) is one of the most common malignancy and primary cause of death in Chinese cancer patients. Recurrence is a major factor leading to treatment failure and low level of 5-year survival rate in GC patients following surgical resection. Therefore, identification of biomarkers with potential in predicting recurrence risk is the key problem of the prognosis in GC patients.<h4>Patients and methods</h4>A total of 74 GC patients were selected for systematic analysis ...[more]

PMID: 22802949

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Project description:Gastric cancer (GC), with high heterogeneity, can be mainly classified into intestinal type and diffuse type according to the Lauren classification system. Although a number of differences were reported between these two types, no study on the Lauren subtype-specific multi-gene signature for evaluation of GC prognosis has been conducted, and the molecular mechanism underlying its poor prognosis has still remained elusive. Therefore, this study aimed to explore subtype-specific multi-gene signature for prognostic prediction in different subtypes of Lauren classification. With combination of the least absolute shrinkage and selection operator (LASSO) algorithm and the Akaike information criterion (AIC), the 3-gene subtype-specific prognostic signature was successfully established in diffuse type GC using GSE62254 dataset. Following the calculation of risk score (RS) based on 3-gene signature, the nomogram models were established to predict 1-, 3-, and 5-year overall survival in diffuse type GC. Moreover, the prognostic predictive nomogram model of diffuse type GC was also proved to be effective for validation of GSE1549 dataset and by a Gene Expression Omnibus (GEO)-based meta-analysis. In the analysis of the correlation between RS and clinical-pathological characteristics, RS and two genes of the 3-gene signature (EMCN and COL4A5) were found to be positively correlated with peritoneal metastasis. Furthermore, EMCN and COL4A5, rather than CCL11, were proved to be able to enhance the adhesion ability of MKN45 and NUGC4 cells to peritoneal mesothelial cell line HMR-SV5. Eventually, it was proved that COL4A5 promoted peritoneal metastasis by activating Wnt signaling pathway, whereas the upregulation of integrin family genes mediated by FAK-AKT/ERK/STAT3 signaling pathway activation is involved in peritoneal metastasis promotion function of EMCN. Taken together, our study identified the subtype-specific 3-gene signature in diffuse type GC, which could effectively predict the patients' OS and might explain the molecular mechanisms in presence of its poor prognosis.

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Dataset Information

Identification of hsa-miR-335 as a prognostic signature in gastric cancer.

Publications

Identification of hsa-miR-335 as a prognostic signature in gastric cancer.

Similar Datasets

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