Identification of Common Potential Therapeutic Targets associated with the progression and prognosis of six Aggressive subtypes of Non-Hodgkin’s Lymphoma using RNA-Seq Analysis and Inhibiting them through Molecular Docking

Abstract

Non hodgkin’s Lymphoma(NHL) is the top most prevalent hematological malignancies constituting a diverse classification of Bcell and T-cell proliferation. It is the eleventh most prevalent disease around the world with a 5.8% incidence and 2.6% mortality rate. The classification of the various subtypes of NHL vary from indolent to aggressive depending upon the metastasis in various tissues organs. Pakistan has a 3.6% incidence rate and 3.4% mortality rate, which is expected to rise in future, hence susceptible. It is possible to treat NHL malignancies with the accurate, immdediate and efficient identification of diagnostic and Prognostic biomarkers. In this investigation, high throughput RNA-Seq data from six aggressive NHLs including diffuse large B-cell, mantle cell lymphoma, Primary Effusion Lymphoma, T-Cell Lymphoblastic Lymphoma, Anaplastic Large-Cell Lymphoma and Burkitt’s Lymphoma were retrieved. Quality Control, Alignment and gene quantification was carried out. Differential as well as common gene expression analysis was performed for fifteen distinct, non-redundant subtype combinations. B-cell lymphoma 2 ( BCL2) and Tumour supressing protein (TP53) were the two novel commonly identified candidate genes. Subsequently, 150 ligands from three chemical databses e.g CHEMBL, BindingDB, and DugBank were used to perform molecular docking with BCL2 and TP53. The top 10 candidate inhibitors for each of the proteins were identified by this research. The most intriguing finding was that 7 of the 10 compounds were present for both proteins. The top three pharmacological targets discovered using computational inhibition with the highest relative binding affinities for BCL2 were ERGOTAMINE, Target-salicylAMP-Ligase, and Murizatoclax, while, Murizatoclax, ERGOTAMINE, and ENZASTAURIN were found for Tp53. For the purpose of studying the proteinligand interaction at the subatomic level, the interaction profile for the complex was generated. Nevertheless, to overcome resistance and response in refractory NHL subtypes, there is a significant need for the scientific community to collaborate together 1 Abstract on the investigation of recently discovered biomarkers for their implementation in clinical practice.