Denoising autoencoder-based bulk and single-cell RNA-sequencing data analyses reveal a comorbidity relationship between Alzheimer’s disease and lung cancer

Abstract

Abstract Numerous investigators have studied the correlation between Alzheimer’s disease (AD) and lung cancer (LC), yet a precise comprehension of their interconnection remains elusive. Prior studies have demonstrated the efficacy of certain targeted therapies for controlling ferroptosis in treating AD and LC. Moreover, ferroptosis plays a role in immune regulation. Therefore, this study aims to investigate the association between AD and LC in terms of ferroptosis and particularly its relevance to immune function. Firstly, bulk RNA sequencing data of AD and LC patients were employed to construct a denoising autoencoder (DAE) model that extracted a representation of ferroptosis-related genes. The representation scores were then utilized to conduct an in-depth investigation of the relationship between the two diseases. Furthermore, as immune function plays a pivotal role in AD and LC, we assessed the association of immune function between two diseases by isolating immune-related from Single-cell RNA sequencing (scRNA-seq) data and constructing a DAE model. Using a DAE model based on bulk RNA and scRNA-seq data, the comorbidity relationship between AD and LC in the context of ferroptosis was identified. Furthermore, we found that immune cells affected by ferroptosis might play an important role in the pathogenesis of this comorbidity.