Abstract:

Objective

To investigate the potential of FAM91A1 as an independent prognostic factor in breast cancer and explore the mechanism.

Methods

The expression of FAM91A1 in various breast cancer subtypes were obtained from the “TCGA” module of the UALCAN database， and the expression profiles and clinical data of 1101 breast cancer patients were downloaded from the TCGA database. The patients were divided into low expression group （n＝550） and high expression group （n＝551） according to the median value of FAM91A1 expression （37.653）. Using R 4.4.1 software， survival analysis was conducted to compare the OS between breast cancer patients with high and low FAM91A1 expression， and Cox regression analysis was used to find the influencing factors of OS in breast cancer patients. The correlation between FAM91A1 and immune checkpoints was analyzed， and Spearman method was used to analyze the correlation between FAM91A1 and tumor mutation burden. The STRING website and GEPIA2 database were used to construct FAM91A1-related gene dataset. The GO and KEGG enrichment analysis were used to find the FAM91A1 function and related pathways. FAM91A1-related ceRNA network was constructed using the MiRTarbase database and validated with the StarBase database.

Results

There was a statistically significant difference in FAM91A1 mRNA expression between normal control， luminal， HER-2-positive， and triple negative breast cancer patients in the TCGA database （P ＜0.001）.The results of the survival analysis indicated no significant difference in OS between FAM91A1 high expression group and low expression group （HR ＝1.36，95%CI：0.91-2.05，P ＝0.133）. Cox regression analysis revealed that age （HR ＝1.453，95%CI：1.128-1.875，P ＝0.004）， clinical grade （HR ＝1.773， 95%CI：1.125-2.794， P ＝0.014）， M stage （HR ＝2.155， 95% CI：1.365-3.403， P＜0.001）， and FAM91A1 expression （HR ＝1.297， 95%CI：1.031-1.631， P ＝0.026）were independent factor affecting OS in1101 breast cancer patients. The expression of immune checkpoints （LGLEC15， LAG3， PDCD1， HAVCR2，CD274， PDCD1LG2） was significantly different between FAM91A1 expression group and low expression group（all P ＜0.001）. The expression of FAM91A1 was positively correlated with tumor mutation burden （P ＜0.001）. The Gene Ontology （GO） functional enrichment analysis revealed that gene datasets related to FAM91A1 were predominantly enriched in the following metabolic processes （small molecule and lipid metabolism）， cellular components （external encapsulated structures， cellular unit cell edges） and molecular functions （enzyme activator activity， GTPase activator activity， and metallopeptidase activity）. In the KEGG pathway enrichment analysis， the genes related to FAM91A1 were predominantly enriched in the ABC transporter protein pathway，fatty acid metabolism pathway，etc. By the online database，one miRNA （hsa-mir-15a-5p） and seven lncRNAs （LINC01128， ERI3-IT1， FGD5-AS1， LINC02035， TUG1， XIST， ARMCX5-GPRASP2） were identified within the FAM91A1-associated ceRNA network.

Conclusions

FAM91A1 may serve as an independent prognostic factor in breast cancer， exhibiting a strong correlation with immune infiltration， ABC transporter protein pathway and fatty acid metabolism.

Key words: Breast neoplasms, Bioinformatics, Prognosis, FAM91A1