Systems Biology and Machine Learning Identify Genetic Overlaps Between Lung Cancer and Gastroesophageal Reflux Disease

One Health and planetary health place emphasis on the common molecular mechanisms that connect several complex human diseases as well as human and planetary ecosystem health. For example, not only lung cancer (LC) and gastroesophageal reflux disease (GERD) pose a significant burden on planetary health, but also the coexistence of GERD in patients with LC is often associated with a poor prognosis. This study reports on the genetic overlaps between these two conditions using systems biology-driven bioinformatics and machine learning-based algorithms. A total of nine hub genes including IGHV1-3, COL3A1, ITGA11, COL1A1, MS4A1, SPP1, MMP9, MMP7, and LOC102723407 were found to be significantly altered in both LC and GERD as compared with controls and with pathway analyses suggesting a significant association with the matrix remodeling pathway. The expression of these genes was validated in two additional datasets. Random forest and K-nearest neighbor, two machine learning-based algorithms, achieved accuracies of 89% and 85% for distinguishing LC and GERD, respectively, from controls using