Associations between serum CA724 and HER2 overexpression among stage II–III resectable gastric cancer patients: an observational study
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Xin-Zu Chen1,2, Wei-Han Zhang1,2,*, Hai-Ning Chen1,*, Jian-Ping Liu3, Du He3, Yang Liu4, Kai Liu1,2, Xiao-Long Chen1,2, Xian-Ming Mo5, Zong-Guang Zhou1, Jian-Kun Hu1,2
1Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, China
2Laboratory of Gastric Cancer, State Key Laboratory of Biotherapy/Collaborative Innovation Center of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
3Department of Pathology, West China Hospital, Sichuan University, Chengdu, China
4West China School of Public Health, Sichuan University, Chengdu, China
5Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China
*These authors are contributed equally to this work
Jian-Kun Hu, e-mail: firstname.lastname@example.org
Xin-Zu Chen, e-mail: email@example.com
Keywords: gastric cancer, CA724, human epidermal growth factor receptor 2, immunohistochemistry, carbohydrate antigen
Received: September 12, 2015 Accepted: February 28, 2016 Published: March 17, 2016
Objectives: Associations between serum tumor biomarkers and human epidermal growth factor receptor 2 (HER2) overexpression among locally advanced gastric cancer patients were yet to be determined and therefore warranted investigation.
Results: A total of 318 patients were analyzed. The odds ratios of CA724 were 4.79 (95% CI 1.55–14.79) and 6.29 (1.40–28.19) in comparing the HER2 (2+/3+) and HER2 (3+) with the negative group, respectively (p < 0.05). A combination of the four biomarkers yielded slightly but not significantly greater areas under the curve (AUC = 0.83; 0.71–0.94) than that of serum CA724 alone (0.80; 0.68–0.91); however, an index generated from the combination had better diagnostic performance with 85.7% sensitivity, 80.4% specificity and 97.8% negative predictive value to predict the strong overexpression of HER2 (3+). CA199, CEA or CA125 alone was not associated with HER2 overexpression. Leave-one-out cross-validation found a consistent association between serum CA724 and HER2 (2+/3+) overexpression.
Methods: Patients undergoing radical gastrectomy from 8/2012 to 12/2013 and with pathological stage II–III gastric cancer were retrospectively analyzed. HER2 expression of the surgical samples was estimated using immunohistochemistry; serum CA724, CA199, CEA and CA125 were preoperatively tested. Internal validation was performed using the leave-one-out approach.
Conclusions: Serum CA724 is significantly associated with the overexpression of HER2 among locally advanced gastric cancer patients. The combination of CA724, CA199, CEA and CA125 is better than serum CA724 alone in predicting HER2 overexpression. External validation and further investigation of the biological mechanisms of these associations are required.
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