Embryonic morphogen nodal is associated with progression and poor prognosis of hepatocellular carcinoma.
BACKGROUND: Nodal, a TGF-β-related embryonic morphogen, is involved in multiple biologic processes. However, the expression of Nodal in hepatocellular carcinoma (HCC) and its correlation with tumor angiogenesis, epithelial-mesenchymal transition, and prognosis is unclear. METHODS: We used real-time...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2014-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3897529?pdf=render |
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| author | Jing Chen Wen-Bin Liu Wei-Dong Jia Ge-Liang Xu Jin-Liang Ma Yun Ren Hao Chen Si-Nan Sun Mei Huang Jian-Sheng Li |
| author_facet | Jing Chen Wen-Bin Liu Wei-Dong Jia Ge-Liang Xu Jin-Liang Ma Yun Ren Hao Chen Si-Nan Sun Mei Huang Jian-Sheng Li |
| author_sort | Jing Chen |
| collection | DOAJ |
| description | BACKGROUND: Nodal, a TGF-β-related embryonic morphogen, is involved in multiple biologic processes. However, the expression of Nodal in hepatocellular carcinoma (HCC) and its correlation with tumor angiogenesis, epithelial-mesenchymal transition, and prognosis is unclear. METHODS: We used real-time PCR and Western blotting to investigate Nodal expression in 6 HCC cell lines and 1 normal liver cell line, 16 pairs of tumor and corresponding paracarcinomatous tissues from HCC patients. Immunohistochemistry was performed to examine Nodal expression in HCC and corresponding paracarcinomatous tissues from 96 patients. CD34 and Vimentin were only examined in HCC tissues of patients mentioned above. Nodal gene was silenced by shRNA in MHCC97H and HCCLM3 cell lines, and cell migration and invasion were detected. Statistical analyses were applied to evaluate the prognostic value and associations of Nodal expression with clinical parameters. RESULTS: Nodal expression was detected in HCC cell lines with high metastatic potential alone. Nodal expression is up-regulated in HCC tissues compared with paracarcinomatous and normal liver tissues. Nodal protein was expressed in 70 of the 96 (72.9%) HCC tumors, and was associated with vascular invasion (P = 0.000), status of metastasis (P = 0.004), AFP (P = 0.049), ICGR15 (indocyanine green retention rate at 15 min) (P = 0.010) and tumor size (P = 0.000). High Nodal expression was positively correlated with high MVD (microvessal density) (P = 0.006), but not with Vimentin expression (P = 0.053). Significantly fewer migrated and invaded cells were seen in shRNA group compared with blank group and negative control group (P<0.05). High Nodal expression was found to be an independent factor for predicting overall survival of HCC. CONCLUSIONS: Our study demonstrated that Nodal expression is associated with aggressive characteristics of HCC. Its aberrant expression may be a predictive factor of unfavorable prognosis for HCC after surgery. |
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| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T18:17:31Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj.art-77c6f093ac6843ca8e6c4f5e1349b3a82022-12-21T22:52:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0191e8584010.1371/journal.pone.0085840Embryonic morphogen nodal is associated with progression and poor prognosis of hepatocellular carcinoma.Jing ChenWen-Bin LiuWei-Dong JiaGe-Liang XuJin-Liang MaYun RenHao ChenSi-Nan SunMei HuangJian-Sheng LiBACKGROUND: Nodal, a TGF-β-related embryonic morphogen, is involved in multiple biologic processes. However, the expression of Nodal in hepatocellular carcinoma (HCC) and its correlation with tumor angiogenesis, epithelial-mesenchymal transition, and prognosis is unclear. METHODS: We used real-time PCR and Western blotting to investigate Nodal expression in 6 HCC cell lines and 1 normal liver cell line, 16 pairs of tumor and corresponding paracarcinomatous tissues from HCC patients. Immunohistochemistry was performed to examine Nodal expression in HCC and corresponding paracarcinomatous tissues from 96 patients. CD34 and Vimentin were only examined in HCC tissues of patients mentioned above. Nodal gene was silenced by shRNA in MHCC97H and HCCLM3 cell lines, and cell migration and invasion were detected. Statistical analyses were applied to evaluate the prognostic value and associations of Nodal expression with clinical parameters. RESULTS: Nodal expression was detected in HCC cell lines with high metastatic potential alone. Nodal expression is up-regulated in HCC tissues compared with paracarcinomatous and normal liver tissues. Nodal protein was expressed in 70 of the 96 (72.9%) HCC tumors, and was associated with vascular invasion (P = 0.000), status of metastasis (P = 0.004), AFP (P = 0.049), ICGR15 (indocyanine green retention rate at 15 min) (P = 0.010) and tumor size (P = 0.000). High Nodal expression was positively correlated with high MVD (microvessal density) (P = 0.006), but not with Vimentin expression (P = 0.053). Significantly fewer migrated and invaded cells were seen in shRNA group compared with blank group and negative control group (P<0.05). High Nodal expression was found to be an independent factor for predicting overall survival of HCC. CONCLUSIONS: Our study demonstrated that Nodal expression is associated with aggressive characteristics of HCC. Its aberrant expression may be a predictive factor of unfavorable prognosis for HCC after surgery.http://europepmc.org/articles/PMC3897529?pdf=render |
| spellingShingle | Jing Chen Wen-Bin Liu Wei-Dong Jia Ge-Liang Xu Jin-Liang Ma Yun Ren Hao Chen Si-Nan Sun Mei Huang Jian-Sheng Li Embryonic morphogen nodal is associated with progression and poor prognosis of hepatocellular carcinoma. PLoS ONE |
| title | Embryonic morphogen nodal is associated with progression and poor prognosis of hepatocellular carcinoma. |
| title_full | Embryonic morphogen nodal is associated with progression and poor prognosis of hepatocellular carcinoma. |
| title_fullStr | Embryonic morphogen nodal is associated with progression and poor prognosis of hepatocellular carcinoma. |
| title_full_unstemmed | Embryonic morphogen nodal is associated with progression and poor prognosis of hepatocellular carcinoma. |
| title_short | Embryonic morphogen nodal is associated with progression and poor prognosis of hepatocellular carcinoma. |
| title_sort | embryonic morphogen nodal is associated with progression and poor prognosis of hepatocellular carcinoma |
| url | http://europepmc.org/articles/PMC3897529?pdf=render |
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