miRNA-218/FANCI is associated with metastasis and poor prognosis in lung adenocarcinoma: a bioinformatics analysis

In this study, tumor microarray analysis was used to screen the key messenger RNAs (mRNAs) and microRNAs related to the progression of lung adenocarcinoma (LUAD), in order to provide a theoretical basis for early diagnosis, therapeutic targets, and prognosis evaluation of patients with LUAD.

The mRNA and miRNA expression datasets came from the Gene Expression Omnibus (GEO) project database. Differentially expressed genes (DEGs) and microRNAs (DEMs) between LUAD tissues and adjacent lung tissue were obtained using GEO2R. The Search Tool for the Retrieval of Interacting Genes website was also employed to construct and visualize the interactions of overlapped DEGs. The overall survival of DEMs was investigated using the Kaplan-Meier plotter. The TargetScan website (http://www.targetscan.org/) was used to verify the relationship between FA Complementation Group I (FANCI) and the expression of miRNA-218 (miR-218). The expression of FANCI was verified using the GEO and Human Protein Atlas databases, as well as Real Time Quantitative PCR using our own samples. Next, we analyzed the relationship between the expression of FANCI and the clinicopathological characteristics as well as the prognosis of patients with LUAD. We also explored whether the FANCI was related to immune cell infiltration in LUAD.

FANCI was identified as a hub gene and associated with poor OS. We found that miR-218 negatively regulates FANCI mRNA expression. At the mRNA expression and protein level, FANCI was more highly expressed in LUAD tissues. The expression of FANCI in LUAD was related to tumor size (χ²=13.96, P<0.001), lymphatic metastasis (χ²=3.88, P<0.05), distant metastasis (χ²=45.39, P<0.001), and stage (χ²=11.03, P<0.05). In addition, the Cox regression model found that FANCI mRNA expression was an independent predictive factor of patient survival (P<0.05). FANCI expression was both weakly related to B cells and neutrophil infiltration in LUAD.

miR-218 may negatively regulate FANCI, and FANCI could promote metastasis via extracellular matrix (ECM) receptor interaction, leading to poor prognosis of LUAD. FANCI may be a key gene to the determine metastasis and poor prognosis in patients with LUAD. Changes in the immune microenvironment may be the mechanism through which FANCI leads to poor prognosis of LUAD.