Expression of glutathione peroxidases 4 in colon adenocarcinoma tissues and its relationship with clinicopathological features and prognosis of patients / 肿瘤研究与临床

ABSTRACT

Objective:To investigate the expression of glutathione peroxidases 4 (GPX4) in colon adenocarcinoma and its relationship with clinicopathological features and prognosis of patients.Methods:The data set of colon adenocarcinoma was obtained from The Cancer Genome Atlas (TCGA) database to analyze the expression of GPX4 in colon adenocarcinoma tissues and its predictive value for overall survival (OS). A total of 93 colon adenocarcinoma tissues and 87 adjacent mucosa tissues after operation from November 2009 to May 2010 provided by the National Human Genetic Resources Sharing Service Platform were selected. The expression of GPX4 protein was detected by using tissue chip immunohistochemistry. The relations between the expression of GPX4 protein and the clinicopathological features and OS of colon adenocarcinoma patients were analyzed. Cox proportional hazards regression model was used to analyze the factors affecting the prognosis. The nomogram for predicting OS rate was established and drawn.Results:The analysis of data from TCGA database showed that in 380 cases of colon adenocarcinoma, the expression of GPX4 in colon adenocarcinoma tissues were higher than that in the normal colonic mucosa tissues [the value of fragments per kilobase of exon per million fragments mapped (FPKM) 85.654 (20.351-356.237) vs. 56.230 (48.783-63.931)], and the difference was statistically significant ( Z = -6.150, P<0.05). The OS in GPX4 high-expression group (FPKM ≥83.614) were poorer than that in GPX4 low-expression group (FPKM < 83.614) (median OS time 84.40 months vs. 94.03 months, 5-year OS rate 58.6% vs. 72.7%), and the difference was statistically significant ( P<0.05). Tissue chip immunohistochemical staining results show that the high-expression rate of GPX4 protein in colon adenocarcinoma tissues was higher than that in adjacent normal tissues [38.0% (35/92) vs. 7.3% (6/82)], and the difference was statistically significant ( χ2 = 22.727, P<0.01); the high-expression rate of GPX4 protein in left colon adenocarcinoma tissues was higher than that in right colon adenocarcinoma tissues [47.2% (25/53) vs. 25.6% (10/39), and the difference was statistically significant ( χ2 = 4.42, P = 0.036); the 5-year OS rate of patients in GPX4 high-expression group was lower than that in GPX4 low-expression group (25.7% vs. 57.9%), and the difference was statistically significant ( χ2 = 9.051, P<0.05). Multivariate Cox proportional hazards regression model analysis showed that lymph node metastasis (stage N 1-N 3) ( HR = 2.241, 95% CI 1.242-4.046, P = 0.007) and high expression of GPX4 ( HR = 2.783, 95% CI 1.598-4.848, P<0.01) were independent factors affecting the poor prognosis of colon adenocarcinoma patients. The above factors were used to establish a nomogram for predicting the prognosis of patients with colon adenocarcinoma, the C index was 0.739, indicating that the nomogram had good predictive performance. Conclusion:The expression of GPX4 is up-regulated in colon adenocarcinoma tissues, and its high expression is related to the malignant biological behavior of the tumor and poor prognosis.