title: PRSS8 methylation and its significance in esophageal squamous cell carcinoma.
abstract: Esophageal cancer is one of the most common cancers worldwide, and the incidence and mortality is increasing rapidly in recent years in China, but the underlying mechanisms are largely unclear. Herein we found that the expression of PRSS8, a serine protease prostasin, is significantly decreased in esophageal squamous cell carcinomas (ESCC) at mRNA and protein levels. The reduction of PRSS8 was well correlated with poor differentiation and shorter survival time. Interestingly, ESCC stromal expression of PRSS8 was significantly correlated with stromal lymphocyte infiltration and cancer progression. Methylation specific PCR showed that PRSS8 was hypermethylated in ESCC tissues and ESCC cell lines, which was linked to the downregulation of PRSS8 expression and decreased activities of PRSS8 promoter. De-methylation agent decitabine was able to restore PRSS8 expression, leading to the inhibition of cancer cell proliferation, motility, migration and cell cycle arrest. However, the restored PRSS8 and its tumor inhibition could be reversed by small interfering RNA targeting PRSS8. Mechanistic study showed that tumor inhibition of PRSS8 may be associated with proliferation- and epithelial mesenchymal transition - related proteins in ESCC cells. In conclusion, our finding showed that PRSS8 methylation and its stromal expression had important clinical significance in ESCC.
authors.affiliation: Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining 272067, China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Bao
authors.affiliation: Department of Immunology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining 272067, China.
authors.forename: Yongchen
authors.initials: Y
authors.lastname: Guo
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Zhiguo
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pathology, The First Affiliated Hospital, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Kai
authors.initials: K
authors.lastname: Li
authors.affiliation: Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining 272067, China.
authors.forename: Yiqiong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pathology, Xinxiang Medical University, Xinxiang 453003, China.
authors.forename: Huijuan
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Huali
authors.initials: H
authors.lastname: Dong
authors.affiliation: Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Kui
authors.initials: K
authors.lastname: Shen
authors.affiliation: Department of Pathology and Institute of Precision Medicine, Jining Medical University, Jining 272067, China.|Department of Pathology, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Wancai
authors.initials: W
authors.lastname: Yang
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects / Q000235:genetics; D019175:DNA Methylation; D000077209:Decitabine; D018572:Disease-Free Survival; D015536:Down-Regulation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics; D034622:RNA Interference; D012689:Sequence Homology, Nucleic Acid; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism; D000099271:Prostasin
chemical_list: D001374:Azacitidine; D000077209:Decitabine; D004791:Enzyme Inhibitors; D012697:Serine Endopeptidases; D000099271:Prostasin
keywords: PRSS8; cancer stroma; esophageal cancer; methylation; survival