The Gene Expression Biomarkers for Chronic Obstructive Pulmonary Disease and Interstitial Lung Disease

Abstract

COPD (chronic obstructive pulmonary disease) and ILD (interstitial lung disease) are two common respiratory diseases. They share similar clinical traits but require different therapeutic treatments. Identifying the biomarkers that are differentially expressed between them will not only help the diagnosis of COPD and ILD, but also provide candidate drug targets that may facilitate the development of new treatment for COPD and ILD. Due to the irreversible complex pathological changes of COPD, there are very limited therapeutic options for COPD patients. In this study, we analyzed the gene expression profiles of two datasets: one training dataset that includes 144 COPD patients and 194 ILD patients, and one test dataset that includes 75 COPD patients and 61 ILD patients. Advanced feature selection methods, mRMR (minimal Redundancy Maximal Relevance) and incremental feature selection (IFS), were applied to identify the 38-gene biomarker. An SVM (support vector machine) classifier was built based on the 38-gene biomarker. Its accuracy, sensitivity, and specificity on training dataset evaluated by leave one out cross-validation were 0.905, 0.896, and 0.912, respectively. And on independent test dataset, the accuracy, sensitivity, and specificity on were as great as and were 0.904, 0.933, and 0.869, respectively. The biological function analysis of the 38 genes indicated that many of them can be potential treatment targets that may benefit COPD and ILD patients.

Unique and shared systemic biomarkers for emphysema in Alpha-1 Antitrypsin deficiency and chronic obstructive pulmonary disease

“…Similar to transforming growth factor-α, heparin-binding EGF-like growth factor and amphiregulin, EGF mediates BTC downstream signaling and results in airway epithelial reprogramming or epithelial to mesenchymal transition (EMT), mucus hypersecretion and airway obliteration, and possible malignant transformation of large and small airways. 33 , 34 BTC ranked 14th in a support vector machine classifier used to diagnose and endotype COPD individuals 35 and it was higher in ex-smokers with COPD than without COPD. 36 Our study reports that BTC is significantly associated with emphysema in AATD.…”

Integrative weighted molecular network construction from transcriptomics and genome wide association data to identify shared genetic biomarkers for COPD and lung cancer

“…The recent biomarker discoveries in intracranial aneurysm [ 25 ], Parkinson disease [ 26 ], Diabetes mellitus [ 27 ] and cancers [ 28 ] once again proves the robustness of bioinformatics methods in analyzing the huge gene expression data. Few studies have attempted to analyze the gene expression changes either in blood samples [ 29 , 30 ] or tissue samples of COPD patients [ 31 , 32 ]. But, none of them attempted to identify blood based genetic biomarkers.…”

Prospects of DNA microarray application in management of chronic obstructive pulmonary disease: A systematic review

“…Boudewijn et al [20] 2017 Affymetrix Nasal epithelial brushings NPHP1, CFAP206, CCDC113, MUC1, CREB3L1, DSP Yao et al [21] 2019 Aglient Peripheral blood HBEGF, DIO2, CLCN3…”