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Opposite functions of GSN and OAS2 on colorectal cancer metastasis, mediating perineural and lymphovascular invasion, respectively.
- Source :
-
PloS one [PLoS One] 2018 Aug 27; Vol. 13 (8), pp. e0202856. Date of Electronic Publication: 2018 Aug 27 (Print Publication: 2018). - Publication Year :
- 2018
-
Abstract
- The present study aimed to identify molecules associated with lymphovascular invasion (LVI) and perineural invasion (PNI) and to examine their biological behavior in colorectal cancer (CRC). LVI- and PNI-associated molecules were identified and verified using sequential processes including (1) identification of 117 recurrence-associated genes differentially expressed on RNA-seq analysis using primary cancer tissues from 130 CRC patients with and without systemic recurrence; (2) analysis of molecules associated with LVI and PNI; (3) assessment of biological properties by measuring proliferation, anoikis, invasion/migration, epithelial-mesenchymal transition and autophagy flux; and (4) verification of disease-free survival using public datasets. Gelsolin (GSN) and 2'-5'-oligoadenylate synthetase 2 (OAS2) were associated with PNI and LVI, respectively. Invasion potential was >2-fold greater in GSN-overexpressing LoVo cells than in control cells (p<0.001-0.005), whereas OAS2-overexpressing RKO cells showed reduced invasion (p<0.001-0.005). GSN downregulated E-cadherin, β-catenin, claudin-1 and snail, and upregulated N-cadherin and ZEB1, whereas OAS2 overexpression had the opposite effects. Several autophagy-related proteins including ATG5-12, ATG6/BECN1, ATG7 and ATG101 were downregulated in GSN-overexpressing LoVo cells, whereas the opposite pattern was observed in OAS2-overexpressing RKO cells. Patients with low GSN expression had significantly higher 5-year recurrence-free survival (RFS) rates than those with GSN overexpression (73.6% vs. 64.7%, p = 0.038), whereas RFS was longer in patients with OAS2 overexpression than in those with underexpression (73.4% vs. 63.7%, p = 0.01). In conclusion, GSN and OAS2 were positively and negatively associated with recurrence, respectively, suggesting their potential value as predictors of recurrence or therapeutic targets in CRC patients.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- 2',5'-Oligoadenylate Synthetase genetics
Apoptosis
Biomarkers, Tumor genetics
Cell Movement
Cell Proliferation
Colorectal Neoplasms genetics
Colorectal Neoplasms metabolism
Gelsolin genetics
Humans
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Recurrence, Local genetics
Neoplasm Recurrence, Local metabolism
Prognosis
Survival Rate
Tumor Cells, Cultured
2',5'-Oligoadenylate Synthetase metabolism
Biomarkers, Tumor metabolism
Colorectal Neoplasms pathology
Gelsolin metabolism
Neoplasm Recurrence, Local pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 13
- Issue :
- 8
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 30148861
- Full Text :
- https://doi.org/10.1371/journal.pone.0202856