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A Seven-microRNA Expression Signature Predicts Survival in Hepatocellular Carcinoma.

Zhang J, Chong CC, Chen GG, Lai PB - PLoS ONE (2015)

Bottom Line: The differential expression of microRNAs (miRNAs) has been associated with the prognosis of various cancers.Seven miRNAs were significantly associated with survival (P value <0.001).Among the seven significant miRNAs, six (hsa-mir-326, hsa-mir-3677, hsa-mir-511-1, hsa-mir-511-2, hsa-mir-9-1, and hsa-mir-9-2) were negatively associated with overall survival (OS), while the remaining one (hsa-mir-30d) was positively correlated.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.

ABSTRACT
Hepatocellular carcinoma (HCC) is the fifth common cancer. The differential expression of microRNAs (miRNAs) has been associated with the prognosis of various cancers. However, limited information is available regarding genome-wide miRNA expression profiles in HCC to generate a tumor-specific miRNA signature of prognostic values. In this study, the miRNA profiles in 327 HCC patients, including 327 tumor and 43 adjacent non-tumor tissues, from The Cancer Genome Atlas (TCGA) Liver hepatocellular carcinoma (LIHC) were analyzed. The associations of the differentially expressed miRNAs with patient survival and other clinical characteristics were examined with t-test and Cox proportional regression model. Finally, a tumor-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate\multivariate Cox regression analyses and KEGG pathway analysis. Results showed that a total of 207 miRNAs were found differentially expressed between tumor and adjacent non-tumor HCC tissues. 78 of them were also discriminatively expressed with gender, race, tumor grade and AJCC tumor stage. Seven miRNAs were significantly associated with survival (P value <0.001). Among the seven significant miRNAs, six (hsa-mir-326, hsa-mir-3677, hsa-mir-511-1, hsa-mir-511-2, hsa-mir-9-1, and hsa-mir-9-2) were negatively associated with overall survival (OS), while the remaining one (hsa-mir-30d) was positively correlated. A tumor-specific 7-miRNAs signature was generated and validated as an independent prognostic predictor. Collectively, we have identified and validated an independent prognostic model based on the expression of seven miRNAs, which can be used to assess patients' survival. Additional work is needed to translate our model into clinical practice.

No MeSH data available.


Related in: MedlinePlus

Heatmap of 207 differentially expressed miRNAs in tumor/non-tumor.The miRNA expression levels are mean-centered across samples, and an unsupervised hierarchical clustering with complete linkage is carried out by Cluster 3.0.
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pone.0128628.g001: Heatmap of 207 differentially expressed miRNAs in tumor/non-tumor.The miRNA expression levels are mean-centered across samples, and an unsupervised hierarchical clustering with complete linkage is carried out by Cluster 3.0.

Mentions: The miRNA expression in the 327 HCC tumor tissues and 43 adjacent non-tumor tissues (Cohort T and N) were investigated, and a total of 207 miRNAs (DEmiRNA) were found to be expressed differentially with p value and FDR less than 0.001 (S1 Table). As outlined in Fig 1, the unsupervised hierarchical clustering with the 207 miRNA expression data clearly discriminated the tumor and adjacent non-tumor samples. Among these 207 miRNAs, 77 miRNAs (31.2%) were up-regulated, while the remaining 130 miRNAs (62.8%) were down-regulated. With regard to the fold change in expression levels, 50 differentially expressed miRNAs showed a greater than three-fold or less than 0.33-fold change in expression levels. Among the 50 miRNAs, 13 miRNAs (26.0%) were up-regulated and 37 miRNAs (74.0%) were down-regulated (Fig 2).


A Seven-microRNA Expression Signature Predicts Survival in Hepatocellular Carcinoma.

Zhang J, Chong CC, Chen GG, Lai PB - PLoS ONE (2015)

Heatmap of 207 differentially expressed miRNAs in tumor/non-tumor.The miRNA expression levels are mean-centered across samples, and an unsupervised hierarchical clustering with complete linkage is carried out by Cluster 3.0.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4457814&req=5

pone.0128628.g001: Heatmap of 207 differentially expressed miRNAs in tumor/non-tumor.The miRNA expression levels are mean-centered across samples, and an unsupervised hierarchical clustering with complete linkage is carried out by Cluster 3.0.
Mentions: The miRNA expression in the 327 HCC tumor tissues and 43 adjacent non-tumor tissues (Cohort T and N) were investigated, and a total of 207 miRNAs (DEmiRNA) were found to be expressed differentially with p value and FDR less than 0.001 (S1 Table). As outlined in Fig 1, the unsupervised hierarchical clustering with the 207 miRNA expression data clearly discriminated the tumor and adjacent non-tumor samples. Among these 207 miRNAs, 77 miRNAs (31.2%) were up-regulated, while the remaining 130 miRNAs (62.8%) were down-regulated. With regard to the fold change in expression levels, 50 differentially expressed miRNAs showed a greater than three-fold or less than 0.33-fold change in expression levels. Among the 50 miRNAs, 13 miRNAs (26.0%) were up-regulated and 37 miRNAs (74.0%) were down-regulated (Fig 2).

Bottom Line: The differential expression of microRNAs (miRNAs) has been associated with the prognosis of various cancers.Seven miRNAs were significantly associated with survival (P value <0.001).Among the seven significant miRNAs, six (hsa-mir-326, hsa-mir-3677, hsa-mir-511-1, hsa-mir-511-2, hsa-mir-9-1, and hsa-mir-9-2) were negatively associated with overall survival (OS), while the remaining one (hsa-mir-30d) was positively correlated.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.

ABSTRACT
Hepatocellular carcinoma (HCC) is the fifth common cancer. The differential expression of microRNAs (miRNAs) has been associated with the prognosis of various cancers. However, limited information is available regarding genome-wide miRNA expression profiles in HCC to generate a tumor-specific miRNA signature of prognostic values. In this study, the miRNA profiles in 327 HCC patients, including 327 tumor and 43 adjacent non-tumor tissues, from The Cancer Genome Atlas (TCGA) Liver hepatocellular carcinoma (LIHC) were analyzed. The associations of the differentially expressed miRNAs with patient survival and other clinical characteristics were examined with t-test and Cox proportional regression model. Finally, a tumor-specific miRNA signature was generated and examined with Kaplan-Meier survival, univariate\multivariate Cox regression analyses and KEGG pathway analysis. Results showed that a total of 207 miRNAs were found differentially expressed between tumor and adjacent non-tumor HCC tissues. 78 of them were also discriminatively expressed with gender, race, tumor grade and AJCC tumor stage. Seven miRNAs were significantly associated with survival (P value <0.001). Among the seven significant miRNAs, six (hsa-mir-326, hsa-mir-3677, hsa-mir-511-1, hsa-mir-511-2, hsa-mir-9-1, and hsa-mir-9-2) were negatively associated with overall survival (OS), while the remaining one (hsa-mir-30d) was positively correlated. A tumor-specific 7-miRNAs signature was generated and validated as an independent prognostic predictor. Collectively, we have identified and validated an independent prognostic model based on the expression of seven miRNAs, which can be used to assess patients' survival. Additional work is needed to translate our model into clinical practice.

No MeSH data available.


Related in: MedlinePlus