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Published on: October 11, 2018
Key Common Genes with LTF and MMP9 Between Sepsis and Relapsed B-Cell Lineage Acute Lymphoblastic Leukemia in
Ying-Ping Xiao1, Yu-Cai Cheng1, Chun Chen1
1Pediatric Hematology Laboratory, Division of Hematology/Oncology, Department of Pediatrics, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518107, China.
Insights
Pediatric sepsis and relapsed B-cell acute lymphoblastic leukemia share key genes, lactotransferrin (LTF) and matrix metallopeptidase 9 (MMP9). These findings offer new diagnostic and therapeutic strategies for these critical childhood diseases.
Area of Science:
- Genetics and Molecular Biology
- Pediatric Oncology
- Infectious Diseases
Background:
- Pediatric sepsis is a severe condition linked to acute lymphoblastic leukemia (ALL) progression and B-cell ALL (B-ALL) relapse.
- Limited research exists on shared genetic factors between pediatric sepsis and relapsed B-ALL.
Purpose of the Study:
- To identify novel common genetic factors and molecular pathways between pediatric sepsis and relapsed B-ALL.
- To explore potential diagnostic biomarkers and therapeutic targets for these conditions.
Main Methods:
- Retrospective analysis of gene expression datasets for pediatric sepsis and relapsed B-ALL from the Gene Expression Omnibus database.
- Identification of differentially expressed genes, construction of protein-protein interaction networks, and application of machine learning models.
- Functional enrichment analysis, transcription factor-mRNA-microRNA network construction, and molecular docking for drug prediction.
Main Results:
- Two shared diagnostic genetic markers, lactotransferrin (LTF) and matrix metallopeptidase 9 (MMP9), were identified and found to be upregulated in both conditions.
- Specificity protein 1 (SP1) was identified as a key transcription factor regulating LTF and MMP9.
- Molecular docking suggested potential therapeutic roles for curcumin with MMP9 and reserpine with LTF.
Conclusions:
- LTF and MMP9 play significant roles in the molecular pathogenesis of pediatric sepsis and relapsed B-ALL.
- These findings provide novel insights for improving clinical diagnosis and developing targeted therapies.
Abstract:
Background: Pediatric sepsis is a life-threatening disease that is associated with the progression of acute lymphoblastic leukemia (ALL) and the recurrence of B-cell ALL (B-ALL). Although previous studies have reported a partial association between sepsis and ALL, there is limited research on the shared genes between pediatric sepsis and relapsed B-ALL. This study aims to further elucidate the more comprehensive and novel common genetic factors and molecular pathways between the two diseases. Methods: Gene expression datasets pertaining to pediatric sepsis (GSE13904, GSE80496) and relapsed B-ALL (GSE3910, GSE28460) were retrieved from the Gene Expression Omnibus database for this retrospective analysis. The initial analysis identified differentially expressed genes common to both pediatric sepsis and relapsed B-ALL. Subsequent investigations employed three complementary approaches: protein-protein interaction networks, molecular complex detection (MCODE) clustering functions, and support vector machine recursive feature elimination model to separately identify the diagnostic biomarkers for each condition. Importantly, key common genes were identified by overlapping the diagnostic genes for pediatric sepsis and relapsed B-ALL. Further characterization involved comprehensive functional analysis through the Metascape platform, construction of transcription factor (TF)-mRNA-microRNA (miRNA) networks, drug prediction, and molecular docking to explore their biological significance and potential therapeutic targets. Results: Comparative analysis of pediatric sepsis-related and relapsed B-ALL-related datasets revealed two shared genetic markers, lactotransferrin (LTF) and matrix metallopeptidase 9 (MMP9), exhibiting diagnostic significance and consistent upregulation in both disease groups. Transcriptional regulatory network analysis identified specificity protein 1 (SP1) as the principal transcription factor capable of coregulating LTF and MMP9 expression. In addition, molecular docking demonstrated high-affinity interactions between curcumin and MMP9 (-7.18 kcal/mol) as well as reserpine and LTF (-5.4 kcal/mol), suggesting their potential therapeutic utility for clinical evaluation. Conclusions: These findings elucidate the molecular pathogenesis involving LTF and MMP9 in pediatric sepsis and relapsed B-ALL, providing novel insights for clinical diagnosis and therapeutic development.

