Primary FSGS and MCD have many clinical as well as histologic similarities at presentation, making separation into these two categories difficult. The common target of injury in both is the podocyte. The distinction between the two disorders is important given the marked difference in terms of response to steroid treatment and long-term outcome. Recently bioinformatics analysis plays an important role in disease studies, facilitating the understanding of pathogenesis by integrating data at the genome level with systematic bioinformatics methods. Consequently, our results may be useful to clinicians to confirm the diagnosis, provide a new method to differential diagnosis and thereby avoid unnecessary or inadequate treatments.
In the present study we found out that, 358 DEGs and 368 DEGs were identified in FSGS and MCD compared with healthy controls. The FSGS and MCD group had 156 shared DEGs, indicating that the two disorders have an important and overlapping genetic component.
GO analysis indicated that MCD and FSGS shared most of the BP terms such as mRNA splicing, RNA polymerase II transcription, mRNA export, insulin stimulus, integrin-mediated signaling pathway, viral process and phagocytosis, which were consistent with previous studies. Integrin-mediated signaling pathway was the most well-known pathway associated with kidney disease. Madhusudhan  once reported that integrin as an essential coreceptor for activated protein C(aPC) that is required for nephroprotective aPC-protease-activated receptors (PARs) signaling in Diabetic nephropathy. In FSGS,Wei  indicated that uPAR is binding to and activating αvβ3 integrins on podocytes, a process that leads to activation of small GTPase Rac-1 which in turns drives podocyte foot process motility and foot process effacement. Kriz  discovered that the activation of αvβ3 integrin becomes a mechanism for the structural and functional changes that they see in podocytes under pathological conditions and which change the capability of podocyte to adapt to physiological events such as a changing filtration pressure and shear forces. Phagocytosis also played an important role in kidney disease. Studies from renal cells in culture, human kidney tissues, and experimental animal models implicate that autophagy regulates many critical aspects of normal and disease conditions in the kidney, such as diabetic nephropathy and other glomerular diseases, tubular injuries, kidney development and aging, cancer, and genetic diseases associated with the kidney .
Insulin signaling has been widely reported in DN. which can control of glucose uptake and podocytes insulin sensitivity, also involve in insulin-dependent cytoskeleton reorganization in podocytes, mediating glomerular albumin permeability then influence podocytes viability .
Through finding out hub genes between two diseases, we discovered that, most of the hub genes shared between them, which indicated these two diseases have the similar pathogenesis. Noteworthy, there were 4 genes as hub genes for FSGS or MCD exclusively. CD2BP2, LSM8 and SNRPB only differential expression in FSGS and SF3A3 only differential expression in MCD.
CD2BP2, originally identified as a binding partner of the adhesion molecule CD2, is a pre-spliceosomal assembly factor that utilizes its glycine-tyrosine-phenylalanine (GYF) domain to co-localize with spliceosomal proteins. So far, its function in vertebrates is unknown. Gesa once discovered that CD2BP2 is critical for embryogenesis and podocyte function. They find out that CD2BP2-depleted podocytes display foot process effacement, and cause proteinuria and ultimately lethal kidney failure in mice, which defines that CD2BP2 as a non-redundant splicing factor essential for embryonic development and podocyte integrity [26–27].
SNRPB is a core component of spliceosome and plays a major role in regulating alternative splicing of the pre-mRNA which has been reported associated with various kinds of cancer. 2019 liu  reported that SNRPB can facilitate Non-small cell lung cancer (NSCLC) tumorigenesis via regulation of RAB26 expression and proposes that the SNRPB/RAB26 pathway may offer a therapeutic vulnerability in NSCLC.
Bruna  revealed the function of SNRPB on splicing and gene expression, through knockdown SNRPB in a GBM cell line followed by RNA sequencing they found that SNRPB was involved in RNA processing, DNA repair, and chromatin remodeling. Additionally, genes and pathways already associated with gliomagenesis, as well as a set of general cancer genes, also presented with splicing and expression alterations.
LSm8 encoded protein consists of a closed barrel shape, made up of five anti-parallel beta strands and an alpha helix. This protein partners with six paralogs to form a hetero heptameric ring which transiently binds U6 small nuclear RNAs and is involved in the general maturation of RNA in the nucleus. LSm8 also Plays role in pre-mRNA splicing as component of the U4/U6-U5 tri-snRNP complex that is involved in spliceosome assembly, and as component of the precatalytic spliceosome (spliceosome B complex).
Splicing factor 3A, subunit 3 (SF3A3) was originally identified from purified spliceosome, and had been known to be a critical component of SF3A RNA splicing complex. SF3A3 appears to localize in nuclear speckles and binds with SF3A1 through its zinc fingers in the N-terminus region. 2017 Zou  reported that SF3A3 might be the regulatory unit of RNA spliceosome. The tumor suppressor gene, cellular stress response 1 (CSR1) through inactivation of SF3A3 to down-regulates the expression of epidermal growth factor receptor and platelet derived growth factor receptor to plays an important role in regulating cell death.
In our study CD2BP2, LSM8, SNRPB and SF3A3 were first reported in FSGS and MCD, and these four genes were only expressed in FSGS or MCD which can be used for future differential diagnosis.