MAN2A1 predicts prognosis and progression through cancer-related pathways in colorectal cancer

Background: Colorectal cancer (CRC) is a common malignant tumor leading to poor prognosis and high mortality. Mannosidase alpha class 2A member 1 (MAN2A1) turns to oncogene through fusing Fer tyrosine kinase (FER) and associates with multiple cancer occurrence. In order to determine whether MAN2A1 can promote tumorigenesis and metastasis in CRC, we conducted a series of studies.

Methods: We obtained gene expression and clinical data of CRC from The Cancer Genome Atlas (TCGA) databases. RNA raw counts data was merged by Python. Batch processing of univariate Cox regression analysis was performed to preliminary identify the genes associated with prognosis. Differentially expressed genes (DEGs) between lymph node metastasis (LNM) patients and non-LNM patients were identified via edgR in Sangerbox tool. Protein-protein interactive (PPI) network was constructed using Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape software. Kaplan-Meier (KM) survival of CRC patients was analyzed by Sangerbox tool. Clinicopathologic characteristics of CRC patients were analyzed by SPSS statistics software. Differences in RNA expression levels of genes were validated in our cohort by real-time polymerase chain reaction (RT-PCR). Analyses of Signaling pathways and gene ontology were explored by gene set enrichment analysis (GSEA).

Results: We first obtained 4,455 genes associated with the prognosis of CRC, and 998 of these genes were also DEGs in CRC between metastatic CRC tissues and in situ tissues. Therein, MAN2A1 expression was downregulated in LNM CRC compared with CRC in situ, also downregulated in CRC compared with adjacent normal tissues, and high gene expression levels of MAN2A1 was associated with better survival.

Conclusions: Our study suggested that MAN2A1 could be a potential biomarker significantly related to prognosis and LNM of CRC patients.