Project description:Circulating microRNAs (miRNAs) in serum may serve as promising diagnostic biomarkers for patients with gastric cancer (GC). Using quantitative reverse transcription polymerase chain reaction (qRT-PCR) based Exiqon panel, we identified 58 differentially expressed miRNAs from 3 GC pool samples and 1 normal control (NC) pool in the initial screening phase. Identified miRNAs were further validated in the training (49 GC VS. 47 NCs) and validation phases (154 GC VS. 120 NCs) using qRT-PCR. Consequently, six serum miRNAs (miR-10b-5p, miR-132-3p, miR-185-5p, miR-195-5p, miR-20a-3p and miR-296-5p) were significantly overexpressed in GC compared with NCs. The areas under the receiver operating characteristic (ROC) curve of the six-miRNA panel were 0.764 and 0.702 for the training and validation phases, respectively. In conclusion, we identified a six-miRNA panel in serum for the detection of GC.
Project description:MicroRNAs (miRNAs), which are stably present in serum, have been reported to be potentially useful for detecting cancer. In the present study, we examined the expression profiles of serum miRNAs in large cohorts to identify the miRNAs that can be used to detect breast cancer in the early stage. We comprehensively evaluated serum miRNA expression profiles using highly sensitive microarray analysis. A total of 1,280 serum samples of breast cancer patients stored in the National Cancer Center Biobank were used. Additionally, 2,836 serum samples were obtained from non-cancer controls and 514 from patients with other types of cancers or benign diseases. The samples were divided to a training cohort including non-cancer controls, other cancers and breast cancer and a test cohort including non-cancer controls and breast cancer. The training cohort was used to identify a combination of miRNAs that detect breast cancer, and the test cohort was used to validate that combination. miRNA expression was compared between breast cancer and non-breast cancer serum , and a combination of five miRNAs (miR-1246, miR-1307-3p, miR-4634, miR-6861-5p, and miR-6875-5p) was found to detect breast cancer. This combination had a sensitivity of 97.3%, specificity of 82.9%, and accuracy of 89.7% for breast cancer in the test cohort Additionally, the combination could detect breast cancer in the early stage (sensitivity of 98.0% for T0).
Project description:The aim of this study was to identify and evaluate exosomal miRNAs in serum as early diagnostic markers for gastric cancer (GC). Methods: Using next-generation sequencing (NGS) and bioinformatics, we identified candidate serum exosomal miRNA markers for early detection of GC in patients. The candidates were further validated by qRT-PCR in 50 newly recruited early-stage GC patients and matched healthy individuals. Results: NGS revealed that the average mappable reads in the RNA libraries were about 6.5 million per patient. A total of 66 up and 13 down-regulated exosomal miRNAs were found in the screened cohort after removal of log2 transformed read counts <5 and p >0.05. In the validation cohort, by comparing candidate exosomal miRNAs levels in early-stage GC patients and healthy individuals, higher levels of miR-92b-3p, let-7g-5p, miR-146b-5p and miR-9-5p were found to be significantly associated with GC. Diagnostic power of the combined panels of the exosomal miRNAs or the combination of exosomal miRNAs and CEA outperformed that of single exosomal miRNA marker for establishing a diagnosis of early-stage GC. In addition, serum levels of exosomal miR-92b-3p were significantly associated with low adhesion, let-7g-5p and miR-146b-5p were significantly correlated with nerve infiltration, and miR146b-5p was statistically correlated with tumor invasion depth in early-stage GC. Conclusions: Serum exosomal miR-92b-3p, -146b-5p, -9-5p, and let-7g-5p may serve as potential noninvasive biomarkers for early diagnosis of GC. Further validation of these candidate exosomal miRNAs in larger experimental cohorts are required in order to confirm the diagnostic values.
Project description:MicroRNAs (miRNAs), which are stably present in serum, have been reported to be potentially useful for detecting cancer. In the present study, we examined the expression profiles of serum miRNAs in large cohorts to identify the miRNAs that can be used to detect breast cancer in the early stage. We comprehensively evaluated serum miRNA expression profiles using highly sensitive microarray analysis. A total of 1,280 serum samples of breast cancer patients stored in the National Cancer Center Biobank were used. Additionally, 2,836 serum samples were obtained from non-cancer controls and 514 from patients with other types of cancers or benign diseases. The samples were divided to a training cohort including non-cancer controls, other cancers and breast cancer and a test cohort including non-cancer controls and breast cancer. The training cohort was used to identify a combination of miRNAs that detect breast cancer, and the test cohort was used to validate that combination. miRNA expression was compared between breast cancer and non-breast cancer serum , and a combination of five miRNAs (miR-1246, miR-1307-3p, miR-4634, miR-6861-5p, and miR-6875-5p) was found to detect breast cancer. This combination had a sensitivity of 97.3%, specificity of 82.9%, and accuracy of 89.7% for breast cancer in the test cohort Additionally, the combination could detect breast cancer in the early stage (sensitivity of 98.0% for T0). 1280 breast cancer serums (74 in training cohort, 1206 in test cohort), 54 benign breast diseases serums in test cohort, 2836 non-cancer control serums (1493 in training cohort, 1343 in test cohort), 514 non-breast benign diseases serums in training cohort. 150 of the non-cancer control serums in training cohort and 412 of the non-breast benign diseases serums in training cohort have been uploaded previously and are avaialable under GSE59856 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE59856).
Project description:BackgroundThe aim of this study was to identify serum miRNAs that discriminate early gastric cancer (EGC) samples from non-cancer controls using a large cohort.MethodsThis retrospective case-control study included 1417 serum samples from patients with EGC (seen at the National Cancer Center Hospital in Tokyo between 2008 and 2012) and 1417 age- and gender-matched non-cancer controls. The samples were randomly assigned to discovery and validation sets and the miRNA expression profiles of whole serum samples were comprehensively evaluated using a highly sensitive DNA chip (3D-Gene®) designed to detect 2565 miRNA sequences. Diagnostic models were constructed using the levels of several miRNAs in the discovery set, and the diagnostic performance of the model was evaluated in the validation set.ResultsThe discovery set consisted of 708 samples from EGC patients and 709 samples from non-cancer controls, and the validation set consisted of 709 samples from EGC patients and 708 samples from non-cancer controls. The diagnostic EGC index was constructed using four miRNAs (miR-4257, miR-6785-5p, miR-187-5p, and miR-5739). In the discovery set, a receiver operating characteristic curve analysis of the EGC index revealed that the area under the curve (AUC) was 0.996 with a sensitivity of 0.983 and a specificity of 0.977. In the validation set, the AUC for the EGC index was 0.998 with a sensitivity of 0.996 and a specificity of 0.953.ConclusionsA novel combination of four serum miRNAs could be a useful non-invasive diagnostic biomarker to detect EGC with high accuracy. A multicenter prospective study is ongoing to confirm the present observations.