J Cancer 2020; 11(4):906-918. doi:10.7150/jca.33766

Research Paper

Comprehensive investigation of p53, p21, nm23, and VEGF expression in hepatitis B virus-related hepatocellular carcinoma overall survival after hepatectomy

Guang-Zhi Zhu1*, Xi-Wen Liao1*, Xiang-Kun Wang1, Yi-Zhen Gong2, Xiao-Guang Liu1, Long Yu1, Chuang-Ye Han1, Cheng-Kun Yang1, Hao Su1, Ke-Tuan Huang1, Ting-Dong Yu1, Jian-Lu Huang1,3, Jia Li4, Zhi-Ming Zeng5, Wei Qin1, Zheng-Qian Liu1, Xin Zhou1, Jun-Qi Liu1, Lei Lu1, Quan-Fa Han1, Li-Ming Shang1, Xin-Ping Ye1, Tao Peng1✉

1. Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
2. Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Zhuang Autonomous Region, People's Republic of China.
3. Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Guangxi Medical University, Nanning, 530031, Guangxi Zhuang Autonomous Region, People's Republic of China.
4. Department of Pathology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, People's Republic of China.
5. Department of Medical Oncology, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region 530021, People's Republic of China.
*Contributed equally

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Citation:
Zhu GZ, Liao XW, Wang XK, Gong YZ, Liu XG, Yu L, Han CY, Yang CK, Su H, Huang KT, Yu TD, Huang JL, Li J, Zeng ZM, Qin W, Liu ZQ, Zhou X, Liu JQ, Lu L, Han QF, Shang LM, Ye XP, Peng T. Comprehensive investigation of p53, p21, nm23, and VEGF expression in hepatitis B virus-related hepatocellular carcinoma overall survival after hepatectomy. J Cancer 2020; 11(4):906-918. doi:10.7150/jca.33766. Available from http://www.jcancer.org/v11p0906.htm

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Abstract

Objective: The goal of our current study is to assess the immunohistochemical of p53, p21, nm23, and VEGF expression in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) prognosis after hepatectomy, as well as the prospective molecular mechanisms of prognostic indicator.

Methods: There were 419 HBV-related HCC patients who were from southern China of Guangxi province and were used to evaluate the immunohistochemical expression for these biomarkers in prognosis. A genome-wide expression microarray dataset of HBV-related HCC were obtained from GSE14520.

Results: In our study, the expression of p53, p21, and nm23 in cancer tissues of patients with hepatitis B-related hepatocellular carcinoma did not affected the clinical outcome of 2 years, 5 years or overall. Patients with high expression of VEGF had a worse overall survival after 2 years of surgery than patients with low expression (adjusted P=0.040, adjusted HR = 1.652, 95% CI = 1.024-2.665). Survival analysis of VEGF in GSE14520 cohort also demonstrated that VEGF mRNA expression also significantly associated with HBV-related HCC OS (adjusted P=0.035, adjusted HR =1.651, 95% CI =1.035-2.634). The prospective molecular mechanisms by co-expression analysis suggested that VEGF might be correlated to regulation of cell proliferation, cell growth and apoptotic process, Rap1 signaling pathway, HIF-1 signaling pathway, PPAR signaling pathway, cell cycle. Whereas the GSEA suggested that VEGF might involve in the regulation of HIF and HIF1A pathway, and TP53 regulation pathway.

Conclusion: Our findings suggested that VEGF might be a prognostic indicator of HBV-related HCC, and we also identified the VEGF prospective molecular mechanisms through the whole genome co-expression and GSEA approaches.

Keywords: hepatitis B virus, hepatocellular carcinoma, overall survival, immunohistochemical, hepatectomy