Pan-cancer analysis reveals NUP37 as a prognostic biomarker correlated with the immunosuppressive microenvironment in glioma.

Ya He,Zhen Li,Hui Zhou,Jingang Li,Lan Shen,Yuetao Wen,Fei Wang,Guangliang Zhang,Wei Fei

doi:10.18632/aging.203862

Abstract

Nucleoporin 37 kDa (NUP37), a member of the nucleoporin family, has been reported to regulate the proliferation and apoptosis of several tumor types. However, its role in the tumor immune microenvironment is unclear. Here, we evaluated the expression, methylation, copy number alteration, and prognostic significance of NUP37 using RNA-seq and clinical data from The Cancer Genome Atlas. We observed higher expression of NUP37 in 28 of 29 tumor types, and high NUP37 expression predicted worse survival status of patients in 15 tumors. Using data from the cBioportal database, we described the gene variation of NUP37 in glioma and pan-cancer. We further assessed the role of NUP37 in the tumor immune microenvironment using immune infiltration data. NUP37 expression was positively associated with the infiltration levels of immunosuppressive cells, such as nTregs, iTregs, and tumor-associated macrophages, and negatively correlated with immune killer cells, such as CD8+ T and NK cells across cancers. Furthermore, NUP37 expression was associated with immune checkpoints and immune regulation-related genes. The half-maximal inhibitory concentrations of anti-cancer drugs were obtained from the Genomics of Drug Sensitivity in the Cancer database. The correlation between half-maximal inhibitory concentration and NUP37 expression was evaluated. The patients with the evaluated expression of NUP37 were resistant to several anti-cancer drugs. These results suggest that NUP37 is a potential oncogene and prognostic biomarker in glioma and pan-cancer. Tumor tissues with high NUP37 expression exist in a relatively immunosuppressive microenvironment and are resistant to several anti-cancer drugs.

Highlights

Glioma is a kind of intracranial malignancies, which has very high recurrence rates and mortality
The results revealed that Nucleoporin 37 kDa (NUP37) was over-expressed by 28 of 29 tumor, it includes ACC, BLCA, BRCA, CHOL, COAD, DLBC, ESCA, glioblastoma multiforme (GBM), HNSC, KICH, KIRC, KIRP, low-grade glioma (LGG), LIHC, LUAD, LUSC, OV, PAAD, PRAD, READ, SKCM, STAD, TGCT, THCA, THYM, UCEC, and UCS, but was lowly conveying in LAML (Figure 1A)
In the study of tumor cell lines, it is necessary to use the data of the Cancer Cell Encyclopedia (CCLE) database to study, and it is found that NUP37 has the highest expression in MESO cell line

Summary

Introduction

Glioma is a kind of intracranial malignancies, which has very high recurrence rates and mortality. Cancer treatment technology has been greatly improved. The progress of medical technology, especially the combination of different therapies, has improved the survival status of cancer patients [3, 4]. Immunotherapy, especially immune checkpoint inhibitors (ICIs), is only effective in a small number of patients. Most studies show that the effect of cancer treatment is related to tumor microenvironment, while relatively speaking, tumor immune microenvironment (TIME) is more important [7,8,9]. The high infiltration level of TAMs and Tregs might predict a favorable response to ICIs treatment in many tumors [11], including brain tumors [12], and lung cancers [13], to name a few

Methods

Results

Conclusion