ABSTRACT
Although it has been proved that the epigenetic modification of DNA and histones is involved in the pathogenesis of systemic lupus erythematosus (SLE), there is no study to explore whether the modification of N6-methyladenosine (m6A) in RNA is involved. In this study, the mRNA levels of m6A "writers" (METTL3, MTEEL14, and WTAP), "erasers" (FTO and ALKBH5), and "readers" (YTHDF2) in peripheral blood were determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The results demonstrated that the mRNA levels of METTL3, WTAP, FTO, ALKBH5, and YTHDF2 in peripheral blood from SLE patients were significantly decreased. The levels of ALKBH5 mRNA in SLE patients were associated with anti-dsDNA, antinucleosome, rash, and ulceration. Multivariate logistic regression analysis showed that the level of ALKBH5 mRNA in peripheral blood is a risk factor of SLE (P < 0.001). Moreover, our results suggested that there was a positive correlation between m6A"writers" (METTL3 and WTAP), "erasers" (FTO and ALKBH5), and "readers" (YTHDF2) in SLE patients. This study suggests that the mRNA level of ALKBH5 in peripheral blood may be involved in the pathogenesis of SLE.
Subject(s)
AlkB Homolog 5, RNA Demethylase/blood , Lupus Erythematosus, Systemic/genetics , Lupus Erythematosus, Systemic/immunology , Adenosine/analogs & derivatives , Adenosine/immunology , Adult , AlkB Homolog 5, RNA Demethylase/genetics , AlkB Homolog 5, RNA Demethylase/immunology , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/blood , Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics , Autoantibodies/blood , Biomarkers/blood , Cell Cycle Proteins/blood , Cell Cycle Proteins/genetics , Female , Gene Expression , Humans , Lupus Erythematosus, Systemic/blood , Male , Methyltransferases/blood , Methyltransferases/genetics , Middle Aged , RNA Splicing Factors/blood , RNA Splicing Factors/genetics , RNA, Messenger/blood , RNA-Binding Proteins/blood , RNA-Binding Proteins/genetics , Reproducibility of ResultsABSTRACT
Lung cancer is the leading reason of cancer-related death from cancer globally for both men and women. Recently, tumor immune heterogeneity has been implicated in cancer clinical outcome. However, this prognostic significance of immune cell types in lung squamous cell carcinoma (LUSC) is unclear and should be systematically investigated. Two microarray datasets (GSE67061 and GSE2088) from the Gene Expression Omnibus (GEO) database were downloaded and then integrated to estimate the fraction of 22 immune cell types by CIBERSORT algorithm. To validate the estimation for LUSC, the data of LUSC TCGA were also assessed in order to determine specific infiltrating immune cell type closely correlated with LUSC patients' survival determined by Cox regression analyses. Immunotherapeutic and chemotherapeutic response between the LUSC patients were also evaluated. T follicular helper cells were obtained by Cox regression analysis to develop the prognostic signature. According to this immune prognostic risk score, immune signature of T follicular helper cells is an independent and specific prognostic signature for predictions of LUSC patient overall survival. Moreover, high-risk group exhibited less expression of N6-methyladenosine (m6A) RNA methylation regulator including ALKBH5, METTL3, HNRNPC and KIAA1429 and was much more sensitive to immunotherapy and chemotherapy. This study suggests that this immune signature is important determinants of prognosis in LUSC and may provide potential prognostic biomarker or therapeutic target for immunotherapeutic and chemotherapeutic development.
