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Prognostic and predictive values of long non-coding RNA LINC00472 in breast cancer.

Shen Y, Katsaros D, Loo LW, Hernandez BY, Chong C, Canuto EM, Biglia N, Lu L, Risch H, Chu WM, Yu H - Oncotarget (2015)

Bottom Line: Our qPCR results showed that high LINC00472 expression was associated with less aggressive breast tumors and more favorable disease outcomes.Patients with high expression of LINC00472 had significantly reduced risk of relapse and death compared to those with low expression.High LINC00472 was also associated with favorable molecular subtypes, Luminal A or normal-like tumors.

View Article: PubMed Central - PubMed

Affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.

ABSTRACT
LINC00472 is a novel long intergenic non-coding RNA. We evaluated LINC00472 expression in breast tumor samples using RT-qPCR, performed a meta-analysis of over 20 microarray datasets from the Gene Expression Omnibus (GEO) database, and investigated the effect of LINC00472 expression on cell proliferation and migration in breast cancer cells transfected with a LINC00472-expressing vector. Our qPCR results showed that high LINC00472 expression was associated with less aggressive breast tumors and more favorable disease outcomes. Patients with high expression of LINC00472 had significantly reduced risk of relapse and death compared to those with low expression. Patients with high LINC00472 expression also had better responses to adjuvant chemo- or hormonal therapy than did patients with low expression. Results of meta-analysis on multiple studies from the GEO database were in agreement with the findings of our study. High LINC00472 was also associated with favorable molecular subtypes, Luminal A or normal-like tumors. Cell culture experiments showed that up-regulation of LINC00472 expression could suppress breast cancer cell proliferation and migration. Collectively, our clinical and in vitro studies suggest that LINC00472 is a tumor suppressor in breast cancer. Evaluating this long non-coding RNA in breast tumors may have prognostic and predictive value in the clinical management of breast cancer.

No MeSH data available.


Related in: MedlinePlus

Meta-analysis of associations between LINC00472 expression and clinicopathological features of breast cancerSummarized odds ratios were estimated using the random-effect model, and the odds ratio in each study was weighted with the variance of probe values (inverse-variance weighted method). A. Lower LINC00472 expression associated with high tumor grade (OR = 2.81; 95% CI: 2.24–3.53), positive lymph node (OR = 1.51; 95% CI: 1.22–1.87), or molecular subtypes of luminal B, Her2 positive and basal-like (OR = 3.80; 95% CI: 2.38–6.07). B. Higher LINC00472 expression associated with ER positive tumors (OR = 0.44; 95% CI: 0.35–0.57), PR positive tumors (OR = 0.44; 95% CI: 0.35–0.55), or Her2 negative tumors (OR = 2.62; 95% CI: 1.76–3.90).
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Figure 2: Meta-analysis of associations between LINC00472 expression and clinicopathological features of breast cancerSummarized odds ratios were estimated using the random-effect model, and the odds ratio in each study was weighted with the variance of probe values (inverse-variance weighted method). A. Lower LINC00472 expression associated with high tumor grade (OR = 2.81; 95% CI: 2.24–3.53), positive lymph node (OR = 1.51; 95% CI: 1.22–1.87), or molecular subtypes of luminal B, Her2 positive and basal-like (OR = 3.80; 95% CI: 2.38–6.07). B. Higher LINC00472 expression associated with ER positive tumors (OR = 0.44; 95% CI: 0.35–0.57), PR positive tumors (OR = 0.44; 95% CI: 0.35–0.55), or Her2 negative tumors (OR = 2.62; 95% CI: 1.76–3.90).

Mentions: Twenty-seven datasets containing clinicopathologic information were identified in the GEO database (Supplementary Table S1). In a meta-analysis, we found higher LINC00472 expression to be associated with well-differentiated tumors (low grades) and less aggressive disease (positive ER or PR, negative lymph nodes, luminal A and normal-like molecular subtypes) (Figures 2A, 2B). In GEO, 4 datasets compared gene expression between normal breast tissues and tumors. The comparison showed higher LINC00472 in normal than in tumor tissues (Supplementary Figure S2). Furthermore, 15 datasets in GEO contained information on various survival outcomes, of which 12 included more than 100 patients individually. We performed survival analysis on these 12 datasets after LINC00472 expression was grouped into 3 categories similar to those of our own study. Of the 12 studies, 9 showed significant individual associations between high LINC00472 and favorable survival outcomes (Supplementary Figure S3). Meta-analysis showed both overall survival (Figure 3A) and disease-free survival (Figure 3B) were significantly improved in patients with high LINC00472 compared to those with low expression. Overall, the results of these analyses were in agreement with our own study.


Prognostic and predictive values of long non-coding RNA LINC00472 in breast cancer.

Shen Y, Katsaros D, Loo LW, Hernandez BY, Chong C, Canuto EM, Biglia N, Lu L, Risch H, Chu WM, Yu H - Oncotarget (2015)

Meta-analysis of associations between LINC00472 expression and clinicopathological features of breast cancerSummarized odds ratios were estimated using the random-effect model, and the odds ratio in each study was weighted with the variance of probe values (inverse-variance weighted method). A. Lower LINC00472 expression associated with high tumor grade (OR = 2.81; 95% CI: 2.24–3.53), positive lymph node (OR = 1.51; 95% CI: 1.22–1.87), or molecular subtypes of luminal B, Her2 positive and basal-like (OR = 3.80; 95% CI: 2.38–6.07). B. Higher LINC00472 expression associated with ER positive tumors (OR = 0.44; 95% CI: 0.35–0.57), PR positive tumors (OR = 0.44; 95% CI: 0.35–0.55), or Her2 negative tumors (OR = 2.62; 95% CI: 1.76–3.90).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4496168&req=5

Figure 2: Meta-analysis of associations between LINC00472 expression and clinicopathological features of breast cancerSummarized odds ratios were estimated using the random-effect model, and the odds ratio in each study was weighted with the variance of probe values (inverse-variance weighted method). A. Lower LINC00472 expression associated with high tumor grade (OR = 2.81; 95% CI: 2.24–3.53), positive lymph node (OR = 1.51; 95% CI: 1.22–1.87), or molecular subtypes of luminal B, Her2 positive and basal-like (OR = 3.80; 95% CI: 2.38–6.07). B. Higher LINC00472 expression associated with ER positive tumors (OR = 0.44; 95% CI: 0.35–0.57), PR positive tumors (OR = 0.44; 95% CI: 0.35–0.55), or Her2 negative tumors (OR = 2.62; 95% CI: 1.76–3.90).
Mentions: Twenty-seven datasets containing clinicopathologic information were identified in the GEO database (Supplementary Table S1). In a meta-analysis, we found higher LINC00472 expression to be associated with well-differentiated tumors (low grades) and less aggressive disease (positive ER or PR, negative lymph nodes, luminal A and normal-like molecular subtypes) (Figures 2A, 2B). In GEO, 4 datasets compared gene expression between normal breast tissues and tumors. The comparison showed higher LINC00472 in normal than in tumor tissues (Supplementary Figure S2). Furthermore, 15 datasets in GEO contained information on various survival outcomes, of which 12 included more than 100 patients individually. We performed survival analysis on these 12 datasets after LINC00472 expression was grouped into 3 categories similar to those of our own study. Of the 12 studies, 9 showed significant individual associations between high LINC00472 and favorable survival outcomes (Supplementary Figure S3). Meta-analysis showed both overall survival (Figure 3A) and disease-free survival (Figure 3B) were significantly improved in patients with high LINC00472 compared to those with low expression. Overall, the results of these analyses were in agreement with our own study.

Bottom Line: Our qPCR results showed that high LINC00472 expression was associated with less aggressive breast tumors and more favorable disease outcomes.Patients with high expression of LINC00472 had significantly reduced risk of relapse and death compared to those with low expression.High LINC00472 was also associated with favorable molecular subtypes, Luminal A or normal-like tumors.

View Article: PubMed Central - PubMed

Affiliation: Cancer Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA.

ABSTRACT
LINC00472 is a novel long intergenic non-coding RNA. We evaluated LINC00472 expression in breast tumor samples using RT-qPCR, performed a meta-analysis of over 20 microarray datasets from the Gene Expression Omnibus (GEO) database, and investigated the effect of LINC00472 expression on cell proliferation and migration in breast cancer cells transfected with a LINC00472-expressing vector. Our qPCR results showed that high LINC00472 expression was associated with less aggressive breast tumors and more favorable disease outcomes. Patients with high expression of LINC00472 had significantly reduced risk of relapse and death compared to those with low expression. Patients with high LINC00472 expression also had better responses to adjuvant chemo- or hormonal therapy than did patients with low expression. Results of meta-analysis on multiple studies from the GEO database were in agreement with the findings of our study. High LINC00472 was also associated with favorable molecular subtypes, Luminal A or normal-like tumors. Cell culture experiments showed that up-regulation of LINC00472 expression could suppress breast cancer cell proliferation and migration. Collectively, our clinical and in vitro studies suggest that LINC00472 is a tumor suppressor in breast cancer. Evaluating this long non-coding RNA in breast tumors may have prognostic and predictive value in the clinical management of breast cancer.

No MeSH data available.


Related in: MedlinePlus