Differences of immune disorders between Alzheimer’s disease and breast cancer based on transcriptional regulation

Abstract

Although chronic inflammation and immune disorders are of great importance to the pathogenesis of both dementia and cancer, the pathophysiological mechanisms are not clearly understood. In recent years, growing epidemiological evidence and meta-analysis data suggest an inverse association between Alzheimer’s disease (AD), which is the most common form of dementia, and cancer. It has been revealed that some common genes and biological processes play opposite roles in AD and cancer; however, the biological immune mechanism for the inverse association is not clearly defined. An unsupervised matrix decomposition two-stage bioinformatics procedure was adopted to investigate the opposite behaviors of the immune response in AD and breast cancer (BC) and to discover the underlying transcriptional regulatory mechanisms. Fast independent component analysis (FastICA) was applied to extract significant genes from AD and BC microarray gene expression data. Based on the extracted data, the shared transcription factors (TFs) from AD and BC were captured. Second, the network component analysis (NCA) algorithm in this study was presented to quantitatively deduce the TF activities and regulatory influences because quantitative dynamic regulatory information for TFs is not available via microarray techniques. Based on the NCA results and reconstructed transcriptional regulatory networks, inverse regulatory processes and some known innate immune responses were described in detail. Many of the shared TFs and their regulatory processes were found to be closely related to the adaptive immune response from dramatically different directions and to play crucial roles in both AD and BC pathogenesis. From the above findings, the opposing cellular behaviors demonstrate an invaluable opportunity to gain insights into the pathogenesis of these two types of diseases and to aid in developing new treatments.

Cracking the Code of Neuronal Cell Fate

“…This evidence supports previous studies proposing its role as a tumor suppressor in various types of cancers [ 186 , 187 ]. In addition, altered expression of SPDEF has been found in Alzheimer’s disease patients and animal models, while a recent association was found between blood-based Spdef methylation and stress response, altered dopaminergic neurotransmission and increased vulnerability to substance abuse, suggesting its role as a biomarker for these pathological conditions [ 188 , 189 , 190 , 191 ].…”

Breast cancer in schizophrenia could be interleukin-33-mediated

“…In recent years, epidemiological evidence of a controversial association between cancer and neurodegenerative diseases has been increasing. Common etiological factors may play opposing roles in the pathogenesis of neurodegeneration and breast cancer[ 14 , 15 ]. Characteristic brain pathology leads to neuronal cell death and neurodegeneration over time, whereas cancer is dominated by the process of unlimited cell proliferation[ 16 , 17 ].…”

Gene biomarker discovery at different stages of Alzheimer using gene co-expression network approach

“…A different study showed that LPP was suppressed considerably in MCI samples in comparison with the healthy ones 60 . Another study named some of the genes that had regulation changes between healthy and AD samples and argued that LPP was one of them 61 . KLF13 was introduced in a neurodegenerative disease study as one of the key regulators in Alzheimer's disease 62 .…”