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BackgroundPrevious studies have demonstrated that transcriptional RNA methyladenosine modification significantly affects tumor initiation and progression. However, clinical implications of N1-methyladenosine (m1A) regulators and their effect on tumor immunity in lung adenocarcinoma (LUAD) are still poorly elucidated.MethodsHerein, the characteristics of somatic mutation, copy number variation (CNV), DNA methylation, and expression levels of m1A regulators were thoroughly analyzed. We classified 955 lung adenocarcinoma patients into different m1A modification patterns based on an unsupervised consensus clustering algorithm. We then calculated the differences in gene expression, prognosis outcomes, and immune profiles among different m1A clusters. Subsequently, we screened differently expressed genes (DEGs) related to prognosis among different m1A clusters. We identified m1A related gene clusters according to the prognosis-related different expressed genes. We further constructed a scoring standard named the m1A score and comprehensively analyzed the survival outcomes, clinical-pathological features, immune microenvironment, treatment responses of immunotherapy, and drug susceptibility in different m1A score groups.ResultsIn total, three different m1A modification patterns were identified, which contained cluster A, B, and C. Among them, cluster A processed the poorest clinical outcomes, the lowest immune cell infiltration rate, and the highest tumor purity score. Then, three m1A gene clusters (gene cluster A, B, C) were speculated. Subsequently, we combined m1A modification patterns and m1A gene cluster to classify lung adenocarcinoma patients into high and low m1A score groups. The low m1A score group was accompanied by higher mortality, higher tumor mutation burden (TMB) and genome mutation frequency, and lower programmed cell death-Ligand 1 (PD-L1) expression and tumor immune dysfunction and exclusion (TIDE) expression. Moreover, the m1A score exhibited positive correlation with almost all immune cells. Finally, common chemotherapeutic and targeted therapy agents exhibited obvious differences in drug susceptibility in different m1A score groups.ConclusionsCollectively, we explored the potential value of m1A regulators in the prognosis and treatment of lung adenocarcinoma in multiple dimensions and provided some preliminary basis for the follow-up study of m1A regulators in lung adenocarcinoma.

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Esophageal cancer is a common malignant tumor in the world, and the aim of this study was to screen key genes related to the development of esophageal cancer using a variety of bioinformatics analysis tools and analyze their biological functions. The data of esophageal squamous cell carcinoma from the Gene Expression Omnibus (GEO) were selected as the research object, processed and analyzed to screen differentially expressed microRNAs (miRNAs) and differential methylation genes. The competing endogenous RNAs (ceRNAs) interaction network of differentially expressed genes was constructed by bioinformatics tools DAVID, String, and Cytoscape. Biofunctional enrichment analysis was performed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG). The expression of the screened genes and the survival of the patients were verified. By analyzing GSE59973 and GSE114110, we found three down-regulated and nine up-regulated miRNAs. The gene expression matrix of GSE120356 was calculated by Pearson correlation coefficient, and the 11696 pairs of ceRNA relation were determined. In the ceRNA network, 643 lncRNAs and 147 mRNAs showed methylation difference. Functional enrichment analysis showed that these differentially expressed genes were mainly concentrated in the FoxO signaling pathway and were involved in the corresponding cascade of calcineurin. By analyzing the clinical data in The Cancer Genome Atlas (TCGA) database, it was found that four lncRNAs had an important impact on the survival and prognosis of esophageal carcinoma patients. QRT-PCR was also conducted to identify the expression of the key lncRNAs (RNF217-AS1, HCP5, ZFPM2-AS1 and HCG22) in ESCC samples. The selected key genes can provide theoretical guidance for further research on the molecular mechanism of esophageal carcinoma and the screening of molecular markers.

Hepatoid adenocarcinoma of the lung (HAL) is an exceptionally rare malignant tumor with prominent hepatocellular carcinoma (HCC)-like characteristics in organs or tissues outside the liver, while there is no tumor in the liver. Most HAL cases have various degrees of serum alpha-fetoprotein (AFP) levels and exhibit a similar origin and clonal evolution process to HCC. We studied a case of HAL without elevating the AFP level by performing whole-exome sequencing (WES) and bioinformatics analyses after surgical resection. Our results showed mutations in two driver genes, NLRP3 and PBX1, and we identified HNRNPR, TP73, CFAP57, COL11A1, RUSC1, SLC6A9, DISC1, NBPF26, and OR10K1 as potential driver mutation genes in HAL. In addition, 76 significantly mutated genes (SMG) were identified after the statistical test of each mutation type on genes.