Evidence-Based Medicine
Copyright ©2014 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Apr 14, 2014; 20(14): 4085-4092
Published online Apr 14, 2014. doi: 10.3748/wjg.v20.i14.4085
Combined detection tumor markers for diagnosis and prognosis of gallbladder cancer
Yun-Feng Wang, Fei-Ling Feng, Xu-Hong Zhao, Zhen-Xiong Ye, He-Ping Zeng, Zhen Li, Xiao-Qing Jiang, Zhi-Hai Peng
Yun-Feng Wang, Zhi-Hai Peng, Department of Hepatobiliary Surgery, Qianfoshan Hospital, Shandong University, Jinan 250014, Shandong Province, China
Yun-Feng Wang, Zhen-Xiong Ye, He-Ping Zeng, Zhen Li, Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
Fei-Ling Feng, Xiao-Qing Jiang, The First Department of Biliary Surgery, Eastern Hepatobiliary Surgery Hospital of the Second Military Medical University, Shanghai 200438, China
Xu-Hong Zhao, Central Experiment Laboratory, Yangpu Hospital, Tongji University School of Medicine, Shanghai 200090, China
Author contributions: Wang YF and Peng ZH conceived the study and drafted the manuscript; Feng FL, Zhao XH, and Ye ZX performed chart review and follow-up of the study; Zeng HP, Li Z, and Jiang XQ helped to draft the manuscript and perform statistical analyses; Wang YF was responsible for the whole study; all authors read and approved the final manuscript.
Correspondence to: Yun-Feng Wang, PhD, Department of General Surgery, Yangpu Hospital, Tongji University School of Medicine, No. 450, Teng Yue Road, Shanghai 200090, China. wangyunfeng197911@163.com
Telephone: +86-21-65690520 Fax: +86-21-65696249
Received: December 26, 2013
Revised: January 23, 2014
Accepted: March 6, 2014
Published online: April 14, 2014
Abstract

AIM: To clarify the value of combined use of markers for the diagnosis of gallbladder cancer and prediction of its prognosis.

METHODS: Serum cancer antigens (CA)199, CA242, carcinoembryonic antigen (CEA), and CA125 levels were measured in 78 patients with gallbladder cancer (GBC), 78 patients with benign gallbladder diseases, and 78 healthy controls using electrochemiluminescence. CA199, CA242, CEA, and CA125 levels and positive rates were analyzed and evaluated pre- and post-operatively. Receiver operator characteristic curves were used to determine diagnostic sensitivity and specificity of GBC. Survival time analysis, including survival curves, and multivariate survival analysis of a Cox proportional hazards model was performed to evaluate independent prognostic factors.

RESULTS: Serum CA242, CA125, and CA199 levels in the GBC group were significantly higher when compared with those in the benign gallbladder disease and healthy control groups (P < 0.01). With a single tumor marker for GBC diagnosis, the sensitivity of CA199 was the highest (71.7%), with the highest specificity being in CA242 (98.7%). Diagnostic accuracy was highest with a combination of CA199, CA242, and CA125 (69.2%). CA242 could be regarded as a tumor marker of GBC infiltration in the early stage. The sensitivity of CA199 and CA242 increased with progression of GBC and advanced lymph node metastasis (P < 0.05). The 78 GBC patients were followed up for 6-12 mo (mean: 8 mo), during which time serum CA199, CA125, and CA242 levels in the recurrence group were significantly higher than in patients without recurrence (P < 0.01). The post-operative serum CA199, CA125, and CA242 levels in the non-recurrence group were significantly lower than those in the GBC group (P < 0.01). Multivariate survival analysis using a Cox proportional hazards model showed that cancer of the gallbladder neck and CA199 expression level were independent prognostic factors.

CONCLUSION: CA242 is a marker of GBC infiltration in the early stage. CA199 and cancer of the gallbladder neck are therapeutic and prognostic markers.

Keywords: Gallbladder cancer, Tumor marker, Combined detection, Diagnosis, Prognosis

Core tip: Detection of serum tumor markers is simple, and has become a common clinical method for tumor screening. However, when these markers are used individually for the diagnosis of gallbladder cancer, inconsistent results have been obtained. The results of the present study suggest that combined detection of serum cancer antigens cancer antigens (CA)125, CA199, and CA242 can increase the specificity of gallbladder cancer (GBC) diagnosis. CA242 could be regarded as a tumor marker of GBC infiltration in the early stage. Multivariate survival analysis showed that cancer of the gallbladder neck and CA199 expression levels were independent prognostic factors.