A Novel RNA N1-methyladenosine Regulator Mediated Methylation Modification Pattern Can Impact the Immune Status and Predict the Prognosis and Drug Sensitivity of Lung Adenocarcinoma

Abstract Background: Lung adenocarcinoma (LUAD) has a high morbidity and mortality. Although the treatment of NSCLC has made progress in recent years, its 5-year overall survival (OS) is about 25 %. In recent years, epigenetic modification has been increasingly regarded as an important marker of cancer. RNA methylation is essentially an epigenetic modification. However, the potential role of m1A modification-related genes in LUAD tumor microenvironment (TME) remains unclear. Methods: In this study, 10 m1A modulators were comprehensively evaluated in 724 GEO-LUAD patients as training set and 474 TCGA-LUAD patients as test group. Then, three subgroups were determined using the consensus clustering method to evaluate the association between m1A modification and TME. The CIBERSORT method was used to evaluate the level of immune cell infiltration. Finally, the m1A score based on PCA algorithm was associated with prognosis, clinical stage, T stage, N stage, TMB and immune cell infiltration, which was statistically significant. In addition, the drug sensitivity of patients with high and low scores is also different, which provides a new idea for clinical treatment. At the same time, our gene protein-protein interaction (PPI) network screened the target gene ALKBH1, and we found that ALHBH1 is an important biomarker for poor prognosis. More importantly, immunohistochemistry and PCR confirmed that ALKBH1 was up-regulated in LUAD, and the higher the expression, the worse the prognosis. Results: The high m1A score of patients had a better prognosis, higher immune cell infiltration, a better response to immunotherapy, and a poorer response to chemotherapy. Conclusion: In summary, the m1A score is expected to become a new tool for evaluating the prognosis of LUAD patients and a candidate biomarker for immunotherapy, chemotherapy and targeted therapy strategies. In addition, we found that ALKBH1 can be used as a biomarker for the prognosis of lung adenocarcinoma and experimentally verified the same results.