ABSTRACT
BACKGROUND: Almost one-third of patients with diffuse large B-cell lymphoma (DLBCL) cannot be cured with initial therapy and will eventually succumb to the disease. Further elaboration of prognostic markers of DLBCL will provide therapeutic targets. IQ motif-containing GTPase activating protein 2 (IQGAP2) acts as a tumour suppressor in hepatocellular, prostate, and gastric cancers. However, the role of IQGAP2 in DLBCL remains unclear. METHODS: We collected mRNA expression data from 614 samples and the corresponding clinical information. The survival time of patients was compared between groups according to the mRNA expression level of IQGAP2. Survival analyses were performed in different subgroups when considering the effect of age, tumour stage, serum lactate dehydrogenase (LDH) concentration, performance status, and the number of extra nodal disease sites. The biological processes associated with IQGAP2-associated mRNAs were analysed to predict the function of IQGAP2. The correlation of IQGAP2 mRNA with immunosuppressive genes and leukocyte infiltration were analysed. RESULTS: The overall survival of patients with increased IQGAP2 mRNA levels was reduced even after aggressive treatment independent of age, tumour stage, serum LDH concentration, performance status, and the number of extra nodal disease sites. Furthermore, the biological processes of IQGAP2-associated mRNAs were mainly immune processes. IQGAP2 mRNA expression was correlated with the expression of immunosuppressive genes and leukocyte infiltration. CONCLUSION: IQGAP2 mRNA is an independent prognostic factor and is related to immunosuppression in DLBCL. This discovery may provide a promising target for further development of therapy.
Subject(s)
Biomarkers, Tumor/genetics , Gene Expression Regulation, Neoplastic/immunology , Lymphoma, Large B-Cell, Diffuse/genetics , Tumor Escape/genetics , ras GTPase-Activating Proteins/genetics , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/metabolism , Cyclophosphamide/therapeutic use , Datasets as Topic , Doxorubicin/therapeutic use , Female , Humans , Lymphoma, Large B-Cell, Diffuse/drug therapy , Lymphoma, Large B-Cell, Diffuse/immunology , Lymphoma, Large B-Cell, Diffuse/mortality , Male , Middle Aged , Oligonucleotide Array Sequence Analysis , Prednisone/therapeutic use , Prognosis , RNA, Messenger/metabolism , RNA-Seq , Retrospective Studies , Rituximab/therapeutic use , Single-Cell Analysis , Survival Analysis , Time Factors , Treatment Outcome , Tumor Microenvironment/genetics , Tumor Microenvironment/immunology , Vincristine/therapeutic use , ras GTPase-Activating Proteins/metabolismABSTRACT
Despite the many recent breakthroughs in cancer research, oncology has traditionally been seen as a distinct field from other diseases. Recently, more attention has been paid to repurposing established therapeutic strategies and targets of other diseases towards cancer treatment, with some of these attempts generating promising outcomes [1, 2]. Recent studies using advanced metabolomics technologies [3] have shown evidence of close metabolic similarities between cancer and neurological diseases. These studies have unveiled several metabolic characteristics shared by these two categories of diseases, including metabolism of glutamine, gamma-aminobutyric acid (GABA), and N-acetyl-aspartyl-glutamate (NAAG) [4-6]. The striking metabolic overlap between cancer and neurological diseases sheds light on novel therapeutic strategies for cancer treatment. For example, 2-(phosphonomethyl) pentanedioic acid (2-PMPA), one of the glutamate carboxypeptidase II (GCP II) inhibitors that prevent the conversion of NAAG to glutamate, has been shown to suppress cancer growth [6, 7]. These promising results have led to an increased interest in integrating this metabolic overlap between cancer and neurological diseases into the study of cancer metabolism. The advantages of studying this metabolic overlap include not only drug repurposing but also translating existing knowledge from neurological diseases to the field of cancer research. This chapter discusses the specific overlapping metabolic features between cancer and neurological diseases, focusing on glutamine, GABA, and NAAG metabolisms. Understanding the interconnections between cancer and neurological diseases will guide researchers and clinicians to find more effective cancer treatments.
Subject(s)
Neoplasms , Organophosphorus Compounds , Dipeptides , Glutamic Acid , Glutamine , Neoplasms/drug therapy , gamma-Aminobutyric AcidABSTRACT
We developed a hybrid nanoimprint-soft lithography technique with sub-15 nm resolution. It is capable of patterning both flat and curved substrates. The key component of the technology is the mold, which consists of rigid features on an elastic poly(dimethylsiloxane) (PDMS) support. The mold was fabricated by imprinting a reverse image onto the PDMS substrate using a UV-curable low-viscosity prepolymer film. Patterns with sub-15-nm resolution were faithfully duplicated on a flat substrate without applying external pressure. Gratings at 200 nm pitch were also successfully imprinted onto the cylindrical surface of a single mode optical fiber with a 125 microm diameter.
