Clinical Significance of Complement and Coagulation Cascades Genes for Patients With Acute Lymphoblastic Leukemia.

Abstract

Introduction: Acute lymphoblastic leukemia (ALL) is the second most common acute leukemia in adults and the 5-year survival remains low.

Methods: We analyzed the gene expression profiles of the complement and coagulation cascades pathway (CCCP) in 998 bone marrow (BM) and 122 peripheral blood (PB) samples of ALL patients and healthy individuals obtained from the TCGA database and evaluated their clinical significance in terms of being diagnostic and prognostic biomarkers.

Results: We identified 18 CCCP genes (SERPINA1, C5AR1, F5, CD55, PLAUR, C3AR1, THBD, CD59, PLAU, VWF, CFD, F13A1, C1QA, C1QB, C1QC, A2M, SERPINE1 and CR2) differentially expressed in the BM samples of ALL patients compared to healthy individuals. The expression levels of CD55, F13A1 and CR2 in BM were linked with the overall survival of ALL patients. While in PB only 11 CCCP genes (e.g., SERPINA1, C5AR1, F5, PLAUR, C3AR1, THBD, CFD, F13A1, C1QA, SERPINE1, and CR2) were differentially expressed and F13A1 was significantly associated with ALL patient survival. Machine learning enabled us to predict ALL using the CCCP genes and the accuracy can reach 0.9701 and 0.9167 using the BM and PB, respectively. Furthermore, using single-cell RNA sequencing, we found that the differential expression of CCCP genes was found with diversity in the BM-derived immune cells of ALL patients.

Conclusion: Our findings suggest that the CCCP genes may play a key role in the progression of ALL and can be used as potential therapeutic targets and diagnostic markers.