Expression And Significance Of A Novel Prognostic Molecule LMO2 In Diffuse Large B-cell Lymphoma

BackgroundDiffuse Large B-cell lymphoma（DLBCL）is the most common aggressive non-Hodgkin lymphoma.Currently,the treatment of DLBCL is mainly CHOP or R-CHOP,which can achieve complete remission in most patients,but there are still some patients with drug resistance.Therefore,this study conducted secondary mining of DLBCL patient data in tumor-related databases to find molecular markers for DLBCL patients’ diagnosis and prognosis improvement.The clinicopathological data of DLBCL patients in our center were retrospectively analyzed,the expression of LMO2 protein was detected by immunohistochemical method,and the clinical significance and prognostic value of LMO2 protein in DLBCL patients were comprehensively evaluated.ObjectiveDiffuse Large B-cell lymphoma（DLBCL）related prognostic molecule LMO2 was mined using tumor-related database to observe the expression of LMO2 protein in DLBCL.To evaluate the clinical relevance and prognostic value of LMO2 protein in DLBCL patients,so as to search for new effective DLBCL prognostic molecule.Methods1.DLBCL patient data set was retrieved by GEO database,and differential gene screening and enrichment analysis were performed.The LASSO regression model and SVM algorithm were constructed to screen the intersection genes of the two models.Through literature review,the target gene was selected as LMO2 protein,and ROC curve and survival curve were drawn.LMO2 protein interaction protein network was analyzed by STRING database.The correlation between LMO2 protein expression and BCL2,BCL6 and MYC protein was analyzed.The correlation between the expression of LMO2 protein and the expression of immune cells was analyzed.2.The clinical data of 47 adult DLBCL cases first diagnosed in the Department of Oncology of the Third Affiliated Hospital of Xinxiang Medical College and the First Affiliated Hospital of Zhengzhou University from January 2019 to January 2022 were retrospectively analyzed.Immunohistochemical methods were used to detect the expression of LMO2,CD86 and CD163 proteins,and analyze the clinicopathological characteristics,immunohistochemical indicators and prognosis of LMO2 protein and patients.Risk stratification was performed according to IPI and NCCN-IPI scores to explore the accuracy of immunohistochemistry combined with IPI and NCCN-IPI scores in predicting the occurrence,development and prognosis of DLBCL.Results1.Two data sets GSE10846 and GSE32918 from GEO database were selected to analyze the data in the two data sets,and 18 differentially expressed genes were obtained.The enrichment analysis found that the genes were mainly enriched in ECM receptor interaction,adhesion,regulation of actin cytoskeleton,sulfur metabolism and other signaling pathways.The intersection of LASSO regression model and SVM algorithm model was constructed to obtain a total of 16 intersection genes.Through literature review and correlation analysis,LMO2 was selected as the target gene.2.Gene expression analysis showed that LMO2 protein expression in tumor tissues was significantly higher than that in normal tissues,and LMO2 protein expression in GBC group was higher than that in ABC group（P < 0.05）.ROC curve analysis showed that the area of LMO2 protein under the curves in the two data sets was 0.781,indicating that LMO2 has a certain accuracy in predicting the prognosis of patients.Survival analysis showed that in dataset GSE10846,patients with high LMO2 protein expression group had longer survival than those with low LMO2 protein expression group（P <0.05）.Analysis of DLBCL data in TCGA database showed that LMO2 protein expression was negatively correlated with BCL2 and MYC protein expression（P < 0.05）.Immunohistochemical microenvironment analysis found that LMO2 protein expression was positively correlated with Macrophages M0,B cells memory and T cells helper.The expression of LMO2 protein was negatively correlated with the expression of monocyte,Dendritic cells activated,Macrophages M2 and other immune cells.3.Among 47 DLBCL patients,22 were male and 25 were female.The patients were14-70 years old,with a median age of 52 years old.There were 17 LMO2 positive cases and 31 LMO2 negative cases,with a positive expression rate of 36.2%.There was no significant difference in OS and PFS between LMO2 positive and negative expression patients（P > 0.05）.Immunohistochemical results and clinical case data were included in univariate analysis and it was found that BCL6 and MYC could be used as prognostic factors of OS and PFS.In multivariate analysis,MYC could be used as an independent prognostic factor affecting patients’ OS,while BCL6,MYC and LMO2 could be used as independent prognostic factors affecting patients’ PFS.The correlation analysis of LMO2 protein expression and immunohistochemical indexes showed that LMO2 protein expression was negatively correlated with BCL2 protein expression,with statistical significance（P < 0.05）.4.In the immunohistochemistry combined with IPI scoring model,the OS and PFS of medium-high risk patients were longer than those of high-risk patients,and the difference was statistically significant（P<0.05）.The immunohistochemistry combined with IPI scoring model could well predict the prognostic time of patients in medium-high risk group and high-risk group.ConclusionThe expression of LMO2 protein was increased in DLBCL,and the expression of LMO2 protein in GBC subgroup was higher than that in ABC subgroup.LMO2 protein can be used as a marker for diagnosis and prognosis of DLBCL patients.LMO2 protein expression can be used as an independent prognostic factor affecting PFS in DLBCL patients,and LMO2 protein expression is negatively correlated with BCL2 protein expression.Immunohistochemistry combined with IPI score has certain clinical significance in predicting the prognosis of high-risk patients in DLBCL.LMO2 plays a dual role in determining the origin and prognosis of DLBCL,and has the important potential of supplementary immunohistochemical diagnosis.