AUTHOR=Yan Qianqian , Zhao Zihao , Liu Dongwei , Li Jia , Pan Shaokang , Duan Jiayu , Dong Jiancheng , Liu Zhangsuo 

TITLE=Integrated analysis of potential gene crosstalk between non-alcoholic fatty liver disease and diabetic nephropathy

JOURNAL=Frontiers in Endocrinology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2022.1032814

DOI=10.3389/fendo.2022.1032814

ISSN=1664-2392

ABSTRACT=Background: Growing evidences indicate that nonalcoholic fatty liver disease (NAFLD) is related to the occurrence and development of diabetic nephropathy (DN). This bioinformatic study aimed to explore optimal cross-talk genes and related pathways between NAFLD and DN.
Methods: Gene expression profiles were downloaded from Gene Expression Omnibus. CIBERSORT algorithm was employed to analysis the similarity of infiltrating immunocytes between two diseases. Protein-protein interaction (PPI) co-expression network and functional enrichment analysis were conducted based on identification of common different expression genes (DEGs). Least absolute shrinkage and selection operator (LASSO) regression and Boruta algorithm were implemented to initially screen cross-talk genes. Machine learning models, including support vector machine, random forest and generalized linear model, were utilized to further identify the optimal cross-talk genes between DN and NAFLD. An integrated network containing cross-talk genes, transcription factors and associated pathways was developed. 
Results: Four gene expression datasets, including GSE66676, GSE48452 for NAFLD and GSE66676, GSE1009 for DN, were involved in this study. There were 80 common DEGs of the two diseases in total. The PPI interwork built with the 80 common genes includes 77 nodes and 83 edges. Ten optimal cross-talk genes were selected by LASSO regression and Boruta algorithm, including CD36, WIPI1, CBX7, FCN1, SLC35D2, CP, ZDHHC3, PTPN3, LPL, and SPP1. Among these genes, the LPL and SPP1 were most significant according to NAFLD-transcription factor network. Five hundred twenty-nine nodes and 1113 edges were comprised in the PPI interwork of activated pathway-gene. In addition, 14 common pathways of these two diseases were recognized using GO analysis, among them, regulation of lipid metabolic process is closely related to both diseases.
Conclusions: This study offers hints that NAFLD and DN exist common pathogenesis, and LPL and SPP1 are the most relevant cross-talk genes. Based on the common pathways and optimal cross-talk genes our proposal carried out further research to disclose the etiology and pathology between the two diseases.
Keyword: nonalcoholic fatty liver disease, diabetic nephropathy, crosstalk, LPL, SPP1, bioinformatics