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COL6A1 promotes metastasis and predicts poor prognosis in patients with pancreatic cancer

Pancreatic cancer is one of the most aggressive cancers worldwide with a high mortality rate. Prognosis remains poor even in this era of advanced medicine mainly due to early metastasis and invasion. The present study aimed to explore and validate predictors of distant metastasis and prognosis in pa...

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Autores principales: Owusu-Ansah, Kwabena Gyabaah, Song, Guangyuan, Chen, Ronggao, Edoo, Muhammad Ibrahim Alhadi, Li, Jun, Chen, Bingjie, Wu, Jian, Zhou, Lin, Xie, Haiyang, Jiang, Donghai, Zheng, Shusen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615918/
https://www.ncbi.nlm.nih.gov/pubmed/31268154
http://dx.doi.org/10.3892/ijo.2019.4825
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author Owusu-Ansah, Kwabena Gyabaah
Song, Guangyuan
Chen, Ronggao
Edoo, Muhammad Ibrahim Alhadi
Li, Jun
Chen, Bingjie
Wu, Jian
Zhou, Lin
Xie, Haiyang
Jiang, Donghai
Zheng, Shusen
author_facet Owusu-Ansah, Kwabena Gyabaah
Song, Guangyuan
Chen, Ronggao
Edoo, Muhammad Ibrahim Alhadi
Li, Jun
Chen, Bingjie
Wu, Jian
Zhou, Lin
Xie, Haiyang
Jiang, Donghai
Zheng, Shusen
author_sort Owusu-Ansah, Kwabena Gyabaah
collection PubMed
description Pancreatic cancer is one of the most aggressive cancers worldwide with a high mortality rate. Prognosis remains poor even in this era of advanced medicine mainly due to early metastasis and invasion. The present study aimed to explore and validate predictors of distant metastasis and prognosis in pancreatic cancer. In our preliminary experiment, we established a novel metastatic pancreatic cancer cell line BxPC-M8 from parent BxPC-3 cells. Via whole genome sequencing, RT-qPCR, western blotting, migration and invasion assays, we initially found that BxPC-M8 shared similar biological characteristics to BxPC-3, but only differed in enhanced metastatic and invasive capabilities with a significant increase in collagen type VI α1 chain (COL6A1) expression. Knockdown of COL6A1 via small interfering RNA led to a significant decrease in migration and invasion of BxPC-M8 cells, suggesting suppressed epithelial-mesenchymal transition. Furthermore, a significant increase in COL6A1 expression was observed in cancerous tissue compared with paracancerous tissue (40.7 vs 3.7, P=0.001). Additionally, its expression was observed to be significantly associated with distant metastasis and vascular invasion at the time of surgery. Multivariate analysis revealed that COL6A1 expression (hazard ratio 1.90, 95% confidence interval 1.04-3.47, P=0.037) is an independent predictor of overall survival (OS). The median OS observed for COL6A1(+) and COL6A1(−) patients was found to be 8±4 and 14±7 months (P=0.021), respectively. Of note, we identified that COL6A1 expression in tissue samples was associated with significantly reduced OS (P=0.001), demonstrating that COL6A1 may serve an important role in the metastatic process and could be considered as a predictor of poor outcomes in patients with pancreatic cancer. In addition, our findings suggest that COL6A1 could be an indicator of distant metastasis and a valid prognostic predictor in such patients; however, further investigation is required.
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spelling pubmed-66159182019-07-30 COL6A1 promotes metastasis and predicts poor prognosis in patients with pancreatic cancer Owusu-Ansah, Kwabena Gyabaah Song, Guangyuan Chen, Ronggao Edoo, Muhammad Ibrahim Alhadi Li, Jun Chen, Bingjie Wu, Jian Zhou, Lin Xie, Haiyang Jiang, Donghai Zheng, Shusen Int J Oncol Articles Pancreatic cancer is one of the most aggressive cancers worldwide with a high mortality rate. Prognosis remains poor even in this era of advanced medicine mainly due to early metastasis and invasion. The present study aimed to explore and validate predictors of distant metastasis and prognosis in pancreatic cancer. In our preliminary experiment, we established a novel metastatic pancreatic cancer cell line BxPC-M8 from parent BxPC-3 cells. Via whole genome sequencing, RT-qPCR, western blotting, migration and invasion assays, we initially found that BxPC-M8 shared similar biological characteristics to BxPC-3, but only differed in enhanced metastatic and invasive capabilities with a significant increase in collagen type VI α1 chain (COL6A1) expression. Knockdown of COL6A1 via small interfering RNA led to a significant decrease in migration and invasion of BxPC-M8 cells, suggesting suppressed epithelial-mesenchymal transition. Furthermore, a significant increase in COL6A1 expression was observed in cancerous tissue compared with paracancerous tissue (40.7 vs 3.7, P=0.001). Additionally, its expression was observed to be significantly associated with distant metastasis and vascular invasion at the time of surgery. Multivariate analysis revealed that COL6A1 expression (hazard ratio 1.90, 95% confidence interval 1.04-3.47, P=0.037) is an independent predictor of overall survival (OS). The median OS observed for COL6A1(+) and COL6A1(−) patients was found to be 8±4 and 14±7 months (P=0.021), respectively. Of note, we identified that COL6A1 expression in tissue samples was associated with significantly reduced OS (P=0.001), demonstrating that COL6A1 may serve an important role in the metastatic process and could be considered as a predictor of poor outcomes in patients with pancreatic cancer. In addition, our findings suggest that COL6A1 could be an indicator of distant metastasis and a valid prognostic predictor in such patients; however, further investigation is required. D.A. Spandidos 2019-06-14 /pmc/articles/PMC6615918/ /pubmed/31268154 http://dx.doi.org/10.3892/ijo.2019.4825 Text en Copyright: © Owusu-Ansah et al. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Owusu-Ansah, Kwabena Gyabaah
Song, Guangyuan
Chen, Ronggao
Edoo, Muhammad Ibrahim Alhadi
Li, Jun
Chen, Bingjie
Wu, Jian
Zhou, Lin
Xie, Haiyang
Jiang, Donghai
Zheng, Shusen
COL6A1 promotes metastasis and predicts poor prognosis in patients with pancreatic cancer
title COL6A1 promotes metastasis and predicts poor prognosis in patients with pancreatic cancer
title_full COL6A1 promotes metastasis and predicts poor prognosis in patients with pancreatic cancer
title_fullStr COL6A1 promotes metastasis and predicts poor prognosis in patients with pancreatic cancer
title_full_unstemmed COL6A1 promotes metastasis and predicts poor prognosis in patients with pancreatic cancer
title_short COL6A1 promotes metastasis and predicts poor prognosis in patients with pancreatic cancer
title_sort col6a1 promotes metastasis and predicts poor prognosis in patients with pancreatic cancer
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6615918/
https://www.ncbi.nlm.nih.gov/pubmed/31268154
http://dx.doi.org/10.3892/ijo.2019.4825
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