MicroRNA-495 (miR-495) is a small non-coding RNA encoded by a gene located on chromosome 14 (14q32.31). Its expression is regulated by the transcription factors EF12 and EF47, in addition to promoter methylation status and the fusion oncoprotein mixed-lineage leukemia‑AF9. Previous studies suggest that miR‑495 is involved in various developmental, immunological and inflammatory processes in healthy tissue, and in the proliferation, invasion, metastasis and drug resistance of cancer cells. The role miR‑495 serves in tumors is controversial. miR‑495 primarily functions as a tumor suppressor; however, in a number of cases it acts as an oncogene. miR‑495 has potential applications as a diagnostic and prognostic marker, and as a therapeutic target for genetic and pharmacological manipulation in the treatment of various diseases.

Background: Post treatment minimal residual disease (MRD) determination contributes to impending relapse prediction, chemotherapy response and clinical outcomes assessment, guiding clinicians to develop reasonable and effective individual chemotherapy options after induction/consolidation. This study was to identify serum candidate peptides for monitoring adult acute myeloid leukemia (AML) MRD.Results: 47 statistically different expressed peptide peaks were obtained in the molecular weight range of 700-10000 Da. Quick classifier (QC) model had optimal distinction efficiency, in the training set with a sensitivity of 90% and a specificity of 93.33%. Peptides were identified as ubiquitin-like modifier activating enzyme 1(UBA1), isoform 1 of fibrinogen alpha chain precursor and platelet factor 4(PF4). The peptide up-regulated in newly diagnosed AML patients were decreased to the normal level after CR. When refractory & relapsed, relative intensity was elevated again. Results were contrary to down-regulated peptide peaks. Western blot demonstrated that levels of the UBA1 protein did not differ between the leukemia and normal cells. Levels of isoform 1 of fibrinogen alpha chain precursor protein and PF4 protein were both decreased in leukemia cells comparing with normal cells. The serum levels of the PF4 in the newly diagnosed AML patients and healthy controls were significantly different. Further correlation analysis did not indicate the correlated relation between platelet counts and PF4 content, the correlation coefficient was 0.097. Kaplan–Meier analyses of overall survival showed that relative intensity of peptides was correlated with patient’s clinical outcome.Conclusions: We speculate the peptides can be used as potential markers for monitoring minimal residual disease and clinical outcome assessment.

The persistence of minimal residual disease (MRD) during therapy is the strongest adverse prognostic factor in acute lymphocytic leukemia (ALL). This study was to identify serum candidate peptides for monitoring MRD in adult ALL. A total of 33 peptides in the molecular weight range of 1000-10000 Da were detected using ClinProt system and statistically different between adult patients with ALL and healthy controls. Quick classifier (QC) algorithm was used to obtain a diagnostic model consisting of five peptides that could discriminate patients with ALL from controls with a high sensitivity (100%) and specificity (96.67%). The peptides in the QC model were identified as fibrinogen alpha chain (FGA), glutathione S-transferase P1 (GSTP1), isoform 1 of fibrinogen alpha chain precursor, platelet factor 4 (PF4) by high pressure/performance liquid chromatography mass spectrometry/mass spectrometry. Relative intensities of the five peptides were compared among ALL different groups for the potential importance of MRD evaluation in ALL. The peptides with increased relative intensities in newly diagnosed (ND) ALL patients were found to be decreased in their relative intensities after complete remission (CR) of adult ALL. When ALL patients were refractory & relapsed (RR), relative intensities of the peptides were elevated again. Peptides with decreased relative intensities in ND and RR ALL patients were found to be increased in their relative intensities when ALL patients achieved CR. The findings were validated by ELISA and western blot. Further linear regression analyses were performed to eliminate the influence of platelet and white blood cell counts on serum protein contents and indicated that there were no correlations between the contents of all four proteins (PF4, connective tissue active peptide III, FGA and GSTP1) and white blood cell or platelet counts in ALL different groups and healthy control. We speculate the five peptides, FGA, isoform 1 of fibrinogen alpha chain precursor, GSTP1, PF4 and connective tissue active peptide III would be potential biomarkers for forecasting relapse, monitoring MRD and evaluating therapeutic response in adult ALL.

Multiple myeloma (MM) is an incurable hematological cancer with a higher rate of relapse. Alterations in the function of long non-coding RNAs (lncRNAs) promote the progression and metastasis of cancer. We carry out this study to explore the expression profile of differently expressed lncRNAs in newly diagnosed MM. The Bone marrows we analyzed were obtained from five MM and five IDA patients (serving as controls). Arraystar Human LncRNA Array V4.0 was used to profile expression of lncRNAs and mRNAs. Gene ontology (GO) and pathway analysis were utilized to understand the biological roles of differently expressed genes, while Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for constructing the lncRNA-mRNA co-expression network. Quantitative polymerase chain reaction (qRT-PCR) was performed to confirm the expressions of dysregulated lncRNAs. Bioinformatic analysis of the lncRNA expression identified >3000 dysregulated lncRNAs (difference ≥ 2-fold) in MM samples. GO and pathway analysis revealed that ECM-receptor and cell cycle pathway-related genes were significantly associated with MM. Four dysregulated lncRNAs were confirmed by qRT-PCR. Among them, the expression of ST3GAL6-AS1, LAMA5-AS1and RP11-175D17.3wereassociated with stage and risk status of MM. On the basis of GEO public database analysis, LAMA5-AS1 was related with an overall survival rate of MM patients. These results reveal the feasible functions of lncRNAs in pathogenesis of MM. Further studies are required to explore whether these lncRNAs could serve as candidate therapeutic targets and new molecular biomarkers for MM.

The bone marrow microenvironment provides an optimal substrate for multiple myeloma (MM) initiation and progression. The soluble component of MM niche is dynamic with the disease states of MM. We formerly employed proteomic profiling to construct a MM model. Four peptides constituting the model were selected by supervised neural network algorithm (SNN). 62 Newly diagnosed (ND) MM and 64 healthy controls (HCs) were picked up for validating the distinguishing capability of the SNN model. Nano-liquid chromatography-electrospray ionization-tandem mass spectrometry was used for peptide identification. MM in different disease states and HCs were choosed for peptides relative intensities comparison. Western blot and ELISA were employed to validate the variability. The sensitivity and specificity of the independent testing data set for blind validation were 93.55% and 92.19%. The relative intensities of three out of the four peptides were increased in ND and refractory and relapse patients but decreased to that level of HCs in complete remission and very good partial remission patients. Relative intensity of the remaining peptide was negatively associated with MM remission. The peptides sequencing results showed that they were derived from dihydropyrimidinase-like 2, fibrinogen alpha chain, platelet factor 4 and alpha-fetoprotein. The potential value of the four peptides in monitoring MM treatment response was arised from their close correlation with MM disease states.