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Identification of novel transmembrane proteins in scirrhous-type gastric cancer by the Escherichia coli ampicillin secretion trap (CAST) method: TM9SF3 participates in tumor invasion and serves as a prognostic factor.
- Source :
-
Pathobiology : journal of immunopathology, molecular and cellular biology [Pathobiology] 2014; Vol. 81 (3), pp. 138-48. Date of Electronic Publication: 2014 Mar 08. - Publication Year :
- 2014
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Abstract
- Objective: Scirrhous-type gastric cancer (GC) is highly aggressive and has a poor prognosis due to rapid cancer cell infiltration accompanied by extensive stromal fibrosis. The aim of this study is to identify genes that encode transmembrane proteins frequently expressed in scirrhous-type GC.<br />Methods: We compared Escherichia coli ampicillin secretion trap (CAST) libraries from 2 human scirrhous-type GC tissues with a normal stomach CAST library. By sequencing 2,880 colonies from scirrhous CAST libraries, we identified a list of candidate genes.<br />Results: We focused on the TM9SF3 gene because it has the highest clone count, and immunohistochemical analysis demonstrated that 46 (50%) of 91 GC cases were positive for TM9SF3, which was observed frequently in scirrhous-type GC. TM9SF3 expression showed a significant correlation with the depth of invasion, tumor stage and undifferentiated GC. There was a strong correlation between TM9SF3 expression and poor patient outcome, which was validated in two separate cohorts by immunostaining and quantitative RT-PCR, respectively. Transient knockdown of the TM9SF3 gene by siRNA showed decreased tumor cell-invasive capacity.<br />Conclusion: Our results indicate that TM9SF3 might be a potential diagnostic and therapeutic target for scirrhous-type GC.<br /> (© 2014 S. Karger AG, Basel.)
- Subjects :
- Adenocarcinoma, Scirrhous diagnosis
Adenocarcinoma, Scirrhous genetics
Aged
Biomarkers, Tumor genetics
Biomarkers, Tumor physiology
Carrier Proteins
Cell Line, Tumor
Cell Movement genetics
Cell Movement physiology
Female
Gene Expression Regulation, Neoplastic drug effects
Humans
Kaplan-Meier Estimate
Male
Neoplasm Invasiveness genetics
Neoplasm Invasiveness physiopathology
Prognosis
Protein Sorting Signals
RNA, Small Interfering pharmacology
Stomach Neoplasms diagnosis
Stomach Neoplasms genetics
Adenocarcinoma, Scirrhous physiopathology
Ampicillin
Escherichia coli
Membrane Proteins genetics
Membrane Proteins physiology
Sequence Analysis, DNA methods
Stomach Neoplasms physiopathology
Subjects
Details
- Language :
- English
- ISSN :
- 1423-0291
- Volume :
- 81
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Pathobiology : journal of immunopathology, molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 24642718
- Full Text :
- https://doi.org/10.1159/000357821