Construction of three‐gene‐based prognostic signature and analysis of immune cells infiltration in children and young adults with B‐acute lymphoblastic leukemia

Abstract

Background Although B‐acute lymphoblastic leukemia (B‐ALL) patients' survival has been improved dramatically, some cases still relapse. This study aimed to explore the prognosis‐related novel differentially expressed genes (DEGs) for predicting the overall survival (OS) of children and young adults (CAYAs) with B‐ALL and analyze the immune‐related factors contributing to poor prognosis. Methods GSE48558 and GSE79533 from Gene Expression Omnibus (GEO) and clinical sample information and mRNA‐seq from Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database were retrieved. Prognosis‐related key genes were enrolled to build a Cox proportional model using multivariate Cox regression. Five‐year OS of patients, clinical characteristic relevance and clinical independence were assessed based on the model. The mRNA levels of prognosis‐related genes were validated in our samples and the difference of immune cells composition between high‐risk and low‐risk patients were compared. Results One hundred and twelve DEGs between normal B cells and B‐ALL cells were identified based on GSE datasets. They were mainly participated in protein binding and HIF‐1 signaling pathway. One hundred and eighty‐nine clinical samples were enrolled in the study, both Kaplan–Meier (KM) analysis and univariate Cox regression analysis showed that CYBB, BCL2A1, IFI30, and EFNB1 were associated with prognosis, CYBB, BCL2A1, and EFNB1 were used to construct prognostic risk model. Moreover, compared to clinical indicators, the three‐gene signature was an independent prognostic factor for CAYAs with B‐ALL. Finally, the mRNA levels of CYBB, BCL2A1, and EFNB1 were significantly lower in B‐ALL group as compared to controls. The high‐risk group had a significantly higher percentage of infiltrated immune cells. Conclusion We constructed a novel three‐gene signature with independent prognostic factor for predicting 5‐year OS of CAYAs with B‐ALL. Additionally, we discovered the difference of immune cells composition between high‐risk and low‐risk groups. This study may help to customize individual treatment and improve prognosis of CAYAs with B‐ALL.

EPH/Ephrin Signaling in Normal Hematopoiesis and Hematologic Malignancies: Deciphering Their Intricate Role and Unraveling Possible New Therapeutic Targets

“…The authors compared DEGs between normal B cells and B-ALL cells and proposed a three-gene signature including EFNB1, along with CYBB and BCL2A1, as an independent prognostic factor for B-ALL. EFNB1 mRNA levels were significantly lower in the B-ALL group compared to controls [155]. While normally EPHB6 is expressed by a very small population of human PB CD4+ or CD8+ T cells and about 1.5% of normal BM lymphocytes, human leukemia/lymphoma cells of T origin demonstrate conserved or increased EPHB6 expression [150,151].…”

“…A characteristic example is that though the role of EPHB6 during normal hematopoiesis has mainly been studied in T cells, specifically in thymic T cell development [98] and T cell-B cell interactions [116], its increased expression has not only been identified in T-cell leukemia/lymphoma [150,151] but also in AML cases [149]. Another paradigm is that of ephrinB1, which has been so far only studied in mouse normal thymic T cell development [99], while research in human B-ALL also suggests its role in human B lymphopoiesis since EFNB1 is downregulated in B-ALL cases, where it can also serve as an independent prognostic factor [155].…”

“…We should also note that the study of EPH/ephrin expression in hematologic malignancies could convey a possible role in disease prognosis. Thus far, decreased expression of EFNB1 has been identified as an independent prognostic factor for B-ALL [155], and EPHB6 expression was shown to be an adverse prognostic marker in CLL [152].…”

“…B-ALL; EFNB1 mRNA levels significantly lower in B-ALL patients compared to controls[155] ALL: EFNB1 hypermethylation[131] …”

Diagnostic implications of ubiquitination-related gene signatures in Alzheimer's disease

“…The Gene Expression Omnibus (GEO) database, established and managed by the National Center for Biotechnology Information (NCBI), encompasses a diverse range of gene expression data, including second-generation sequencing data, chip sequencing data, single-cell sequencing data, and more 12 . We selected and downloaded dataset GSE5281 from the GEO database, which included 87 AD samples and 74 normal samples.…”