ena-STUDY-UFPA-14-10-2014-15:02:23:363-48
High-throughput Sequencing of miRNAs reveals a tissue signature in gastric cancer and suggests novel potential biomarkers
Gastric cancer has a high incidence and mortality; however, the use of biomarkers for its clinical management remains limited. miRNAs are biomarkers with potential applications in the identification of the risk, prognosis and therapeutic targets. We performed four ultra-deep miRnomes sequencing of gastric adenocarcinoma samples (classified by Lauren system as intestinal type T1N0M0, T1N1M0, T4N1M0 and diffuse T1N0M0) and one miRnome of a gastric antrum sample without tumor. We observed that a small set (20 miRNAs) of those were responsible for approximately 80% of total miRNAs expression in every studied tissue, these might represent a microRNA tissue signature. hsa-miR-135b and hsa-miR-29c were able to discriminate normal antrum from gastric cancer, since they were differentially expressed in every tumor sample compared to antrum sample without tumor (p-value < 0.01 and fold change > 5). These findings were validated in additional samples of tumors and non-tumor gastric tissues by quantitative Real Time PCR. Additionally, we identified seven (7) highly expressed miRNAs exhibiting statistically significant differences in at least two tumor samples (p-value < 0.01 and fold change > 5) compared to antrum without tumor. These results could generate future clinical applications using miRNAs in the field of gastric cancer. Mainly, hsa-miR-135b and hsa-miR-29c revealed great potential as biomarkers of gastric adenocarcinoma occurrence, with the ability to identify individuals at a higher risk of developing this cancer, and could be even used as therapeutic targets to allow individualized clinical management.
Gastric cancer has a high incidence and mortality; however, the use of biomarkers for its clinical management remains limited. miRNAs are biomarkers with potential applications in the identification of the risk, prognosis and therapeutic targets. We performed four ultra-deep miRnomes sequencing of gastric adenocarcinoma samples (classified by Lauren system as intestinal type T1N0M0, T1N1M0, T4N1M0 and diffuse T1N0M0) and one miRnome of a gastric antrum sample without tumor. We observed that a small set (20 miRNAs) of those were responsible for approximately 80% of total miRNAs expression in every studied tissue, these might represent a microRNA tissue signature. hsa-miR-135b and hsa-miR-29c were able to discriminate normal antrum from gastric cancer, since they were differentially expressed in every tumor sample compared to antrum sample without tumor (p-value < 0.01 and fold change > 5). These findings were validated in additional samples of tumors and non-tumor gastric tissues by quantitative Real Time PCR. Additionally, we identified seven (7) highly expressed miRNAs exhibiting statistically significant differences in at least two tumor samples (p-value < 0.01 and fold change > 5) compared to antrum without tumor. These results could generate future clinical applications using miRNAs in the field of gastric cancer. Mainly, hsa-miR-135b and hsa-miR-29c revealed great potential as biomarkers of gastric adenocarcinoma occurrence, with the ability to identify individuals at a higher risk of developing this cancer, and could be even used as therapeutic targets to allow individualized clinical management.