1. Department of Integrative Medicine, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.
2. Department of Oncology, The People's Hospital of Danyang, Affiliated Danyang Hospital of Nantong University, Jiangsu 212300, China.
*These authors contributed equally to this work.
Objective: This report aimed to investigate the potential mechanism of polymeric immunoglobulin receptor (PIGR) in promoting cancer development in hepatocellular carcinoma (HCC).
Methods: PIGR expression was investigated in Gene Expression Omnibus (GEO), Oncomine, The Cancer Genome Atlas (TCGA) and The Human Protein Atlas (HPA) databases. Relationships between PIGR and HCC survival and clinico-pathological features were conducted in TCGA. RNAseq of PIGR overexpression and knockdown samples in Bel-7404 cells were performed for identifying potential mechanisms.
Results: PIGR was significantly overexpressed in tumors compared to nontumors and in HCC serum peripheral blood mononuclear cells (PBMC) than in healthy individuals (all p < 0.05). In TCGA, PIGR was highly altered in 14% HCC patients. PIGR upregulation was significantly associated with poor disease-free survival (p < 0.05). More patients recurred/progressed in PIGR altered group compared to unaltered group (p < 0.01). PIGR was significantly higher in HCC patients with incomplete cirrhosis (p < 0.001) and established cirrhosis (p < 0.05). Fewer patients had N0 lymph node stage in PIGR altered group than those in the unaltered group (p < 0.05). PIGR RNAseq revealed that ribosome signaling was the common pathway in PIGR overexpression and PIGR knockdown samples. RNAseq analysis indicated that RPL10, RPL10A, RPL12, RPL19, RPL36, RPL38, RPL41, RPL6, RPL8, RPS12, RPS14, RPS15A, RPS2, RPS27A and RPSA were significantly upregulated in PIGR overexpression group and downregulated in PIGR underexpression group (all p < 0.05).
Conclusions: Aberrant PIGR was associated with HCC recurrence, and PIGR stimulated ribosome pathway might be a potential mechanism.
Keywords: polymeric immunoglobulin receptor, hepatocellular carcinoma, disease-free survival, recurrence, ribosome