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.