Pan-Cancer Analyses of the Tumor Microenvironment Reveal That Ubiquitin-Conjugating Enzyme E2C Might Be a Potential Immunotherapy Target.

Guang-Zhao Huang,Ting-Ru Shao,Juan Wu,Chen Zou,Xiao-Zhi Lv,Ze-Qun Chen,Yi-Long Ai,Xiaofeng Yang

doi:10.1155/2021/9250207

Abstract

Increasing evidence indicated that the tumor microenvironment (TME) played a crucial role in cancer initiation and progression. Ubiquitin-conjugating enzyme E2C (UBE2C) was differentially expressed in many cancer types. However, the immunological and prognostic roles of UBE2C were unclear. Differentially expressed genes (DEGs) of 29 cancer types were downloaded from GEPIA2 and 4 cancer types failed to download owing to no DEGs. Furthermore, the gene expression profiles, mutation data, and survival data of 33 cancer types were obtained from UCSC Xena. Clinical stage relevance, tumor mutational burden (TMB), TME relevance analysis, and gene set enrichment analysis (GSEA) of DEGs in 33 cancer types were performed. And DEGs were identified in oral squamous cell carcinoma (OSCC) by biological experiments. Previous studies indicated that UBE2C was related to the prognosis of many cancers. In our study, the higher UBE2C expression level meant a terminal clinical stage in 8 cancer types and the expression level of UBE2C was related to TMB in 20 cancer types. In addition, both immune relevance analysis and GSEA showed that UBE2C might participate in immune response in many cancers. Furthermore, the UBE2C mRNA level and protein level were all identified as upregulated in OSCC cell lines and tissues. UBE2C was differentially expressed in many cancer types and related to the pathogenesis and TME of many cancers, which might be a potential diagnostic and therapeutic biomarker.

Highlights

Cancers are severe public health problems all over the world and one of the most common leading causes of death
Ubiquitin-conjugating enzyme E2C (UBE2C) was the only differentially expressed gene in many cancer types (Table 1) according to the GEPIA 2 database. 4 cancer types including PCPG, SARC, MESO, and UVM failed to download owing to no Differentially expressed genes (DEGs) in GEPIA 2
Univariate Cox regression analysis in 33 cancer types showed that UBE2C might be a prognostic biomarker in many cancers according to Overall survival (OS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) (Figure S1)

Summary

Introduction

Cancers are severe public health problems all over the world and one of the most common leading causes of death. A study showed that an estimated 1,762,450 new cancer cases and 606,880 cancer deaths occurred in the United States in 2019 [2]. In China, there were approximately 4.3 million new cancer cases and 2.9 million new cancer deaths in 2018 [3]. With the increase of various cancer morbidity, it is imperious to understand the potential mechanism of tumorigenesis and tumor progression and identify effective biomarkers for cancer diagnosis and therapy. For the past 20 years, studies have indicated that inflammatory immune cells played a crucial role in cancer-related inflammation [4]. Hanahan and Weinberg revealed that tumor-associated inflammation exists in different stages of tumorigenesis and contributes to genomic instability, epigenetic modification, induction of cancer cell proliferation, enhancement of tumor antiapoptotic pathways, stimulation of angiogenesis, and

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