Multiple Myeloma-related Biomarker Screening And Clinical Research Based On CeRNA Network

Objective: In this study,we intend to find lnc RNAs differentially expressed in MM patients and healthy control populations through bioinformatics analysis,use the ce RNA regulatory network theory to explore the miRNAs combined with them and their downstream target genes,and then collect MM clinical samples for verification,the clinical value of the target gene as a molecular marker of MM was discussed through correlation analysis with clinical characteristic indexes and multivariate logistic regression analysis for efficacy judgment.It is expected to provide a basis for the early diagnosis,efficacy evaluation and prognosis of MM in the future.Methods: Download the gene expression data set of multiple myeloma and healthy control population through online GEO database,screen the differentially expressed lnc RNA and m RNA using the bioinformatics analysis method,and search for miRNAs with binding sites with DElnc RNA through the ce RNA theory,after that,target genes predicted to be miRNAs in three different databases were used as target m RNA,and then DEm RNA and target m RNA were intersected to enrich and analyze the target genes in the intersection.Through analysis and literature review,target m RNA,miRNA and lnc RNA were finally determined to form a ce RNA network regulation axis of lnc RNA-miRNA-m RNA.Collect peripheral blood and bone marrow samples of patients with multiple myeloma,peripheral blood samples of healthy control population and bone marrow samples of patients with acute myeloid leukemia,detect and verify the expression of three target genes by qRT-PCR method,and analyze the difference of target gene expression in peripheral blood of patients with multiple myeloma and healthy control population,to compare whether the expression trend of the target gene in the bone marrow samples of MM patients is consistent with that in the peripheral blood at the same time,and the difference between the target gene expression in the bone marrow samples of MM patients and that of acute myeloid leukemia patients,as well as the changes in the expression of the three target genes in different disease states.At the same time,we collected the clinical and pathological data of multiple myeloma patients and did the correlation analysis with the target gene expression,and then conducted the multi factor logistic regression analysis on the total effective rate ORR of multiple myeloma patients.Results: 1.The competitive endogenous RNA network of multiple myeloma was successfully constructed,and the regulatory axis of HCG11-miR-17-5p-CDKN1 A ce RNA network related to multiple myeloma was explored.2.The results of qRT-PCR showed that: compared with the healthy control group,the relative expression level of HCG11 in the peripheral blood of MM patients was significantly increased,the difference was statistically significant,the expression level of miR-17-5p was significantly decreased,and the expression level of CDKN1 A was significantly increased.The expression of HCG11,CDKN1 A and miR-17-5p in bone marrow samples of multiple myeloma patients and peripheral blood samples at the same time showed the same trend.3.Compared with the relative expression level of HCG11 and CDKN1 A in bone marrow samples of patients with acute myeloid leukemia,the expression level in bone marrow samples of MM patients was significantly increased,while the expression level of miR-17-5p was significantly decreased.4.When the expression level of lnc RNA HCG11 was compared between different clinical groups of MM,the statistical analysis showed that the total P value was 0.0037,the difference was statistically significant,and it could be considered that the average value of each group was not the same.The total P value of the relative expression of miR-17-5p among multiple groups was also less than 0.05,indicating that the mean expression of miR-17-5p among the groups was not the same.5.HCG11 expression was significantly correlated with the proportion of bone marrow plasma cells,M protein content,serum globulin content,platelet count and M protein typing;CDKN1A expression and bone marrow plasma cell ratio,M protein content,serum albumin content,serum globulin content,hemoglobin content β The content of 2-microglobulin was significantly correlated with the type of M protein;The expression level of miR-17-5p was significantly correlated with the quantity of24 h urine protein.In multivariate analysis,the clinical indicators that have a true causal relationship with the target gene expression include bone marrow plasma cell ratio,M protein content,serum globulin content,and platelet count.HCG11 expression was positively correlated with CDKN1 A expression.6.The increase of M protein content was the blocking factor for the increase of ORR with statistical significance;The high expression of CDKN1 A was a significant impediment to the increase of ORR;The high expression of HCG11 was a statistically significant impediment to the increase of ORR.Conclusion(s):1.The ceRNA regulatory network and HCG11-miR-17-5p-CDKN1 A regulatory axis of MM patients were successfully predicted based on the online database,and their expression relationship was verified by clinical samples.2.The trend of target gene expression in bone marrow samples and peripheral blood samples of the same patient is consistent,and peripheral blood samples can be used to replace bone marrow samples to detect target genes.HCG11,miR-17-5p and CDKN1 A may be specifically expressed in MM.The expression of HCG11 will change with different disease states.3.HCG11 has the potential as a therapeutic evaluation and prognostic indicator,and CDKN1 A has the potential as a therapeutic target for multiple myeloma.