Canopy Homolog 2 Expression Predicts Poor Prognosis in Hepatocellular Carcinoma with Tumor Hemorrhage
Background/Aims: Canopy homolog 2 (CNPY2) is a signature gene highly associated with tumor progression, including hepatocellular carcinoma (HCC). The presence of tumor hemorrhage (TH) implies a fast-growing and worse tumor microenvironment. We examined a possible association between CNPY2 levels and...
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| Format: | Article |
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Cell Physiol Biochem Press GmbH & Co KG
2018-11-01
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| Series: | Cellular Physiology and Biochemistry |
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| Online Access: | https://www.karger.com/Article/FullText/495048 |
| _version_ | 1811277203409731584 |
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| author | Dong Wang Zhi-Ming Wang Sai Zhang Hai-Jun Wu Yi-Ming Tao |
| author_facet | Dong Wang Zhi-Ming Wang Sai Zhang Hai-Jun Wu Yi-Ming Tao |
| author_sort | Dong Wang |
| collection | DOAJ |
| description | Background/Aims: Canopy homolog 2 (CNPY2) is a signature gene highly associated with tumor progression, including hepatocellular carcinoma (HCC). The presence of tumor hemorrhage (TH) implies a fast-growing and worse tumor microenvironment. We examined a possible association between CNPY2 levels and TH and evaluated their prognostic values in patients with HCC. Methods: CNPY2 mRNA and protein levels were respectively determined in two independent cohorts of HCC specimens using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry of tissue microarrays. Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of HCC. CNPY2 knockout HCC cell lines were established by the CRISPR/Cas9 gene editing system, and the functional role of CNPY2 in HCC cell proliferation and growth was examined in vitro and in vivo. Results: qRT-PCR showed that CNPY2 expression was significantly higher in HCC tumor tissue than in adjacent non-tumor tissue. Immunohistochemistry of HCC tissue microarrays demonstrated that CNPY2 expression was significantly correlated with TH and clinicopathological features indicating worse HCC progression. The prognostic value of CNPY2 expression and TH was validated by Cox proportional hazards analyses. Furthermore, CNPY2 knockout resulted in the significant suppression of MHCC97H cell proliferation, tumor growth, and hemorrhage. Bioinformatics analysis revealed that CNPY2 was closely associated with the expression levels of 6 positive impact genes in HCC, namely, ROMO1, BOLA2, HSF1, ATG4B, ATF4, and DENR, which are implicated in the regulation of the tumor microenvironment. Conclusion: CNPY2 is an oncogene that plays a critical role in the progression of HCC with TH. CNPY2 could be exploited as a novel prognostic marker and potential target for therapeutic intervention in HCC. |
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| issn | 1015-8987 1421-9778 |
| language | English |
| last_indexed | 2024-04-13T00:12:39Z |
| publishDate | 2018-11-01 |
| publisher | Cell Physiol Biochem Press GmbH & Co KG |
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| series | Cellular Physiology and Biochemistry |
| spelling | doaj.art-82040f9d122a44cdb2580e98043ebb8f2022-12-22T03:11:03ZengCell Physiol Biochem Press GmbH & Co KGCellular Physiology and Biochemistry1015-89871421-97782018-11-015062017202810.1159/000495048495048Canopy Homolog 2 Expression Predicts Poor Prognosis in Hepatocellular Carcinoma with Tumor HemorrhageDong WangZhi-Ming WangSai ZhangHai-Jun WuYi-Ming TaoBackground/Aims: Canopy homolog 2 (CNPY2) is a signature gene highly associated with tumor progression, including hepatocellular carcinoma (HCC). The presence of tumor hemorrhage (TH) implies a fast-growing and worse tumor microenvironment. We examined a possible association between CNPY2 levels and TH and evaluated their prognostic values in patients with HCC. Methods: CNPY2 mRNA and protein levels were respectively determined in two independent cohorts of HCC specimens using quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry of tissue microarrays. Kaplan-Meier survival and Cox regression analyses were executed to evaluate the prognosis of HCC. CNPY2 knockout HCC cell lines were established by the CRISPR/Cas9 gene editing system, and the functional role of CNPY2 in HCC cell proliferation and growth was examined in vitro and in vivo. Results: qRT-PCR showed that CNPY2 expression was significantly higher in HCC tumor tissue than in adjacent non-tumor tissue. Immunohistochemistry of HCC tissue microarrays demonstrated that CNPY2 expression was significantly correlated with TH and clinicopathological features indicating worse HCC progression. The prognostic value of CNPY2 expression and TH was validated by Cox proportional hazards analyses. Furthermore, CNPY2 knockout resulted in the significant suppression of MHCC97H cell proliferation, tumor growth, and hemorrhage. Bioinformatics analysis revealed that CNPY2 was closely associated with the expression levels of 6 positive impact genes in HCC, namely, ROMO1, BOLA2, HSF1, ATG4B, ATF4, and DENR, which are implicated in the regulation of the tumor microenvironment. Conclusion: CNPY2 is an oncogene that plays a critical role in the progression of HCC with TH. CNPY2 could be exploited as a novel prognostic marker and potential target for therapeutic intervention in HCC.https://www.karger.com/Article/FullText/495048Hepatocellular carcinomaCanopy homolog 2Tumor hemorrhageMetastasis |
| spellingShingle | Dong Wang Zhi-Ming Wang Sai Zhang Hai-Jun Wu Yi-Ming Tao Canopy Homolog 2 Expression Predicts Poor Prognosis in Hepatocellular Carcinoma with Tumor Hemorrhage Cellular Physiology and Biochemistry Hepatocellular carcinoma Canopy homolog 2 Tumor hemorrhage Metastasis |
| title | Canopy Homolog 2 Expression Predicts Poor Prognosis in Hepatocellular Carcinoma with Tumor Hemorrhage |
| title_full | Canopy Homolog 2 Expression Predicts Poor Prognosis in Hepatocellular Carcinoma with Tumor Hemorrhage |
| title_fullStr | Canopy Homolog 2 Expression Predicts Poor Prognosis in Hepatocellular Carcinoma with Tumor Hemorrhage |
| title_full_unstemmed | Canopy Homolog 2 Expression Predicts Poor Prognosis in Hepatocellular Carcinoma with Tumor Hemorrhage |
| title_short | Canopy Homolog 2 Expression Predicts Poor Prognosis in Hepatocellular Carcinoma with Tumor Hemorrhage |
| title_sort | canopy homolog 2 expression predicts poor prognosis in hepatocellular carcinoma with tumor hemorrhage |
| topic | Hepatocellular carcinoma Canopy homolog 2 Tumor hemorrhage Metastasis |
| url | https://www.karger.com/Article/FullText/495048 |
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