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The impact of high co-expression of Sp1 and HIF1α on prognosis of patients with hepatocellular cancer

  • Authors:
    • Liang Liu
    • Ping Ji
    • Ning Qu
    • Wei‑Lin Pu
    • Dao‑Wen Jiang
    • Wei‑Yan Liu
    • Ya‑Qi Li
    • Rong‑Liang Shi
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China, Shanghai Public Health Clinical Center, Key Laboratory of Medical Molecular Virology of MOE/MOH, Fudan University, Shanghai 201508, P.R. China, Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China, Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433, P.R. China, Department of General Surgery, Minhang Hospital, Fudan University, Shanghai 201199, P.R. China, Department of Colorectal Surgery, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 504-512
    |
    Published online on: May 26, 2016
       https://doi.org/10.3892/ol.2016.4634
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Abstract

Transcription factor specificity protein 1 (Sp1) and hypoxia-inducible factor 1α (HIF1α) serve vital roles in tumor growth and metastasis. The present study aimed to evaluate the impact of co‑expression of Sp1 and HIF1α on the prognosis of patients with hepatocellular cancer (HCC) using The Cancer Genome Atlas (TCGA) database and to validate the association between the expression levels of Sp1/HIF1α in HCC specimens and patient survival using immunohistochemical analysis. A total of 214 eligible patients with HCC from TCGA database were collected for the study. The expression profile of Sp1 and HIF1α were obtained from the TCGA RNAseq database. Clinicopathological characteristics, including age, height, weight, gender, race, ethnicity, family cancer history, serum α‑fetoprotein (AFP), surgical procedures and TNM stage were collected. The Cox proportional hazards regression model and Kaplan‑Meier curves were used to assess the relative factors. Receiver operating characteristic (ROC) curves for cancer‑specific survival (CSS) prediction were plotted to compare the prediction ability of expression of Sp1 and HIF1α and their co‑expression. The location and expression of Sp1 and HIF1α in the HCC tissues were detected by immunohistochemistry (IHC) to verify the association between these two genes and CSS. The results demonstrated that the expressions of Sp1 and HIF1α were significantly increased in the succumbed group (P=0.001), compared with the surviving group. The CSS rates were 60.1% at 3 years (1,067 days), 35.8% at 5 years (1,823 days) and 9.5% at 10 years (3,528 days). Multivariate Cox regression analysis demonstrated that only the high expression levels of Sp1 and HIF1α (≥2x103) were independent predictors for cancer mortality, with P=0.001 and P=0.029, respectively. The area under the curve for the ROC was found to be higher using the combination testing for two genes (0.751) in predicting cancer mortality, compared to a single gene (0.632 for Sp1 and 0.717 for HIF1α). Based on the cutoff points for gene expression, patients were divided into 3 groups: G1 (both genes <2x103), G2 (either gene ≥2x103) and G3 (both genes ≥2x103). The risk of cancer mortality increased with high expression of genes, and G3 exhibited a greater risk than G2 when compared with the G1 group (HR=5.420, 95% CI 2.767‑10.616, P=0.001; HR=3.270, 95% CI 1.843‑5.803, P=0.001). The IHC staining results indicated that patients who died of cancer presented with significantly higher expression levels of these genes compared with those that did not (P=0.001). In summary, high expression levels of Sp1 and HIF1α in HCC tissues were associated with poor prognosis; in particular, the co-expression of these two genes increased the risk of cancer mortality.
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Copy and paste a formatted citation
Spandidos Publications style
Liu L, Ji P, Qu N, Pu WL, Jiang DW, Liu WY, Li YQ and Shi RL: The impact of high co-expression of Sp1 and HIF1α on prognosis of patients with hepatocellular cancer. Oncol Lett 12: 504-512, 2016.
APA
Liu, L., Ji, P., Qu, N., Pu, W., Jiang, D., Liu, W. ... Shi, R. (2016). The impact of high co-expression of Sp1 and HIF1α on prognosis of patients with hepatocellular cancer. Oncology Letters, 12, 504-512. https://doi.org/10.3892/ol.2016.4634
MLA
Liu, L., Ji, P., Qu, N., Pu, W., Jiang, D., Liu, W., Li, Y., Shi, R."The impact of high co-expression of Sp1 and HIF1α on prognosis of patients with hepatocellular cancer". Oncology Letters 12.1 (2016): 504-512.
Chicago
Liu, L., Ji, P., Qu, N., Pu, W., Jiang, D., Liu, W., Li, Y., Shi, R."The impact of high co-expression of Sp1 and HIF1α on prognosis of patients with hepatocellular cancer". Oncology Letters 12, no. 1 (2016): 504-512. https://doi.org/10.3892/ol.2016.4634
Copy and paste a formatted citation
x
Spandidos Publications style
Liu L, Ji P, Qu N, Pu WL, Jiang DW, Liu WY, Li YQ and Shi RL: The impact of high co-expression of Sp1 and HIF1α on prognosis of patients with hepatocellular cancer. Oncol Lett 12: 504-512, 2016.
APA
Liu, L., Ji, P., Qu, N., Pu, W., Jiang, D., Liu, W. ... Shi, R. (2016). The impact of high co-expression of Sp1 and HIF1α on prognosis of patients with hepatocellular cancer. Oncology Letters, 12, 504-512. https://doi.org/10.3892/ol.2016.4634
MLA
Liu, L., Ji, P., Qu, N., Pu, W., Jiang, D., Liu, W., Li, Y., Shi, R."The impact of high co-expression of Sp1 and HIF1α on prognosis of patients with hepatocellular cancer". Oncology Letters 12.1 (2016): 504-512.
Chicago
Liu, L., Ji, P., Qu, N., Pu, W., Jiang, D., Liu, W., Li, Y., Shi, R."The impact of high co-expression of Sp1 and HIF1α on prognosis of patients with hepatocellular cancer". Oncology Letters 12, no. 1 (2016): 504-512. https://doi.org/10.3892/ol.2016.4634
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