Response prediction to oxaliplatin plus 5‑fluorouracil chemotherapy in patients with colorectal cancer using a four‑protein immunohistochemical model

  • Authors:
    • Junjie Gu
    • Zhe Li
    • Jianfeng Zhou
    • Zhao Sun
    • Chunmei Bai
  • View Affiliations

  • Published online on: June 14, 2019     https://doi.org/10.3892/ol.2019.10474
  • Pages: 2091-2101
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Abstract

The response of cancer patients to oxaliplatin combined with 5‑fluorouracil (5‑FU) is difficult to predict. It has been reported that carcinoma‑associated fibroblasts (CAFs) could induce AKT and ERK phosphorylation, and upregulate survivin expression in colorectal cancer (CRC) cells, which could lead to oxaliplatin plus 5‑FU resistance. A total of 71 patients with advanced CRC (aCRC) treated with oxaliplatin plus 5‑FU were included in the present study. These patients comprised 46 chemotherapy responders and 25 non‑responders. The expression levels of α‑smooth muscle actin (α‑SMA), phosphorylated (p)‑AKT, p‑ERK and survivin were determined by immunohistochemical evaluation of paraffin‑embedded samples from patients. A predictive model was established using a Probabilistic Neural Network model. The high expression of α‑SMA, p‑AKT and survivin in patients with aCRC were associated with oxaliplatin plus 5‑FU resistance (P<0.001, P=0.023 and P=0.001, respectively). Furthermore, patients with stage IV CRC exhibiting high expression levels of α‑SMA and survivin experienced a reduced progression‑free survival time compared with patients with low expressions of α‑SMA and survivin (5.5 vs. 15.0 months; 5.5 vs. 15.0 months; P=0.005 and P=0.001, respectively). Stage IV CRC and high survivin expression predicted a reduced overall survival time compared with that for patients with stage IV CRC and low survivin expression (50.0 vs. 15.0 months; P<0.001). Patients with α‑SMA, p‑AKT, p‑ERK and survivin overexpression were more likely to present with intrinsic resistance to the oxaliplatin plus 5‑FU regimen (the accuracies of modeling, validation and prediction were 83.7, 92.9 and 85.7%, respectively). In conclusion, the multifactorial predictive biomarker model of α‑SMA, p‑AKT, p‑ERK and survivin expression for patients with aCRC to predict intrinsic resistance to oxaliplatin plus 5‑FU regimens is of great efficiency and accuracy. Patients with high expression of this predictive model may be intrinsically resistant to the oxaliplatin and 5‑FU regimen.
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August-2019
Volume 18 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Gu J, Li Z, Zhou J, Sun Z and Bai C: Response prediction to oxaliplatin plus 5‑fluorouracil chemotherapy in patients with colorectal cancer using a four‑protein immunohistochemical model. Oncol Lett 18: 2091-2101, 2019
APA
Gu, J., Li, Z., Zhou, J., Sun, Z., & Bai, C. (2019). Response prediction to oxaliplatin plus 5‑fluorouracil chemotherapy in patients with colorectal cancer using a four‑protein immunohistochemical model. Oncology Letters, 18, 2091-2101. https://doi.org/10.3892/ol.2019.10474
MLA
Gu, J., Li, Z., Zhou, J., Sun, Z., Bai, C."Response prediction to oxaliplatin plus 5‑fluorouracil chemotherapy in patients with colorectal cancer using a four‑protein immunohistochemical model". Oncology Letters 18.2 (2019): 2091-2101.
Chicago
Gu, J., Li, Z., Zhou, J., Sun, Z., Bai, C."Response prediction to oxaliplatin plus 5‑fluorouracil chemotherapy in patients with colorectal cancer using a four‑protein immunohistochemical model". Oncology Letters 18, no. 2 (2019): 2091-2101. https://doi.org/10.3892/ol.2019.10474