MicroRNAs (miRNAs) have key roles in breast cancer progression, and their expression levels are heterogeneous across individual breast cancer patients. Traditional methods aim to identify differentially expressed miRNAs in populations rather than in individuals and are affected by the expression intensities of miRNAs in different experimental batches or platforms. Thus it is urgent to conduct miRNA differential expression analysis at an individual level for further personalized medicine research. We proposed a straightforward method to determine the differential expression of each miRNA in an individual patient by utilizing the reversal expression order of miRNA pairs between two conditions (cancer and normal tissue). We applied our method to breast cancer miRNA expression profiles from The Cancer Genome Atlas and two other independent data sets. In total, 292 miRNAs were differentially expressed in individual breast cancer patients. Using the differential expression profile of miRNAs in individual patients, we found that the deregulations of miRNA tend to occur in specific breast cancer subtypes. We investigated the coordination effect between the miRNA and its target, based on the hypothesis that one gene function can be changed by copy number alterations of the corresponding gene or deregulation of the miRNA. We revealed that patients exhibiting an upregulation of hsa-miR-92b and patients with deletions of PTEN did not tend to overlap, and hsa-miR-92b and PTEN coordinately regulated the pathway of ‘cell cycle' and so on. Moreover, we discovered a new prognostic signature, hsa-miR-29c, whose downregulation was associated with poor survival of breast cancer patients.

This study aims to assess the metabolomic profile and related histopathological outcomes of rat plasma after chronic low-dose exposure to dichlorvos (DDVP). A total of 120 male Wistar rats were treated with 0, 2.4, 7.2, and 21.6 mg/kg of body weight/day DDVP continuously for 24 weeks by drinking water. Rat plasma samples were collected at different time-points to measure the metabolomic profiles by ultra-performance liquid chromatography-mass spectrometry (UPLC-MS). Liver tissue analysis was performed to correlate histopathological outcome status to plasma metabolomics. Significant changes in some of the metabolites were found in all the treated groups compared with the control group. LysoPC (15:0/0:0), LysoPC (16:0/0:0), LysoPC (17:0/0:0), LysoPC (0:0/18:0), sphingosine, sphinganine, C16 sphinganine, C17 sphinganine, and arachidonic acid were decreased in the treated groups. LysoPE (16:0/0:0) was increased after dosing with DDVP. Histopathological test outcomes coincided with the plasma metabolomic-profile analysis results obtained by UPLC-MS. The livers were damaged following chronic exposure to DDVP. Abnormal changes in some lipids in the plasma, such as LysoPC (0:0/18:0), were closely related to liver dysfunction. Therefore, metabolomic analysis provides the unique advantages of unveiling the mechanisms of DDVP.