Abstract
RNA methylation is a novel epigenetic modification that can be used to evaluate tumor prognosis. However, the underlying mechanisms are unclear. This study aimed to investigate the genetic characteristics of 5-methylcytosine (m5C) and N1-methyladenosine (m1A) regulators in lung squamous cell carcinoma (LUSC) and the prognostic value and immune-related effects of m5C regulators. To this end, we selected the public LUSC dataset from the Cancer Genome Atlas and Gene Expression Omnibus. The least absolute shrinkage and selection operator regression model was used to identify prognostic risk signatures. We used the UALCAN and Human Protein Atlas databases to study the expression of target gene mRNA/protein expression. Furthermore, the Tumor Immune Single Cell Hub and the Tumor Immune Estimation Resource were used to evaluate the degree of immune cell infiltration. Most of the m5C and m1A regulators showed significantly different expression between LUSC and normal samples. The m5C regulators were associated with poor prognosis. In addition, a prognostic risk signature was developed based on two m5C regulators, NOP2/Sun RNA methyltransferase 3 (NSUN3), and NOP2/Sun RNA methyltransferase 4 (NSUN4). Compared with normal lung tissues, the expression of NSUN3 and NSUN4 in the LUSC TCGA dataset was increased, which was related to clinicopathological characteristics and survival. NSUN3 and NSUN4 were related to the infiltration of six major immune cells; especially NSUN3, which was closely related to CD8+ T cells, while NSUN4 was closely related to neutrophils. Our findings suggest that m5C regulators can predict the clinical prognosis risk and regulate the tumor immune microenvironment in LUSC.
Highlights
Lung cancer is the leading cause of cancer-related deaths worldwide
The results showed that most of the m5C regulators were differently expressed between lung squamous cell carcinoma (LUSC) and normal tissues (Figure 1A)
It may be due to the uneven distribution of sample size, but there were no significant differences in the expression of NOP2/Sun RNA methyltransferase 4 (NSUN4) in different races, smoking, or TP53 mutations. These results suggested that NOP2/Sun RNA methyltransferase 3 (NSUN3) and NSUN4 were closely related to clinicopathological features and may be the oncogenes in LUSC
Summary
Lung cancer is the leading cause of cancer-related deaths worldwide. 1.8 million people are diagnosed with lung cancer, and 1.6 million people die from the disease [1, 2]. 85% of lung cancer patients have the non-small cell lung cancer (NSCLC) subtype [3]. More than half of the patients diagnosed with lung cancer die within one year after diagnosis, and the 5-year survival rate is approximately 17.8%. NSCLC includes three types: adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Lung squamous cell carcinoma (LUSC), which accounts for about 40% of NSCLC, is closely related to smoking and economic levels [4]. Compared with lung adenocarcinoma (LUAD), LUSC has a poor clinical prognosis and lacks targeted drugs. A more comprehensive understanding of the molecular mechanism of LUSC progression is essential for the development of new treatment methods
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