J Cancer 2017; 8(8):1338-1346. doi:10.7150/jca.18030

Research Paper

Serum IgG4:IgG Ratio Predicts Recurrence of Patients with Hepatocellular Carcinoma after Curative Resection

Jiong Wu1*, Xiao-Lu Ma1*, Lu Tian1, Chun-Yan Zhang1, Bei-Li Wang1, Yu-Yi Hu1, Xing-Hui Gao1, Yan Zhou1, Min-Na Shen1, Yin-Fei Peng1, Bai-Shen Pan1, Jian Zhou2, Jia Fan2, Xin-Rong Yang2✉, Wei Guo1✉

1. Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, P. R. China;
2. Department of Liver Surgery, Liver Cancer Institute, Zhongshan hospital, Fudan University, Shanghai 200032, P. R. China.
* These authors contributed equally to this manuscript.

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Wu J, Ma XL, Tian L, Zhang CY, Wang BL, Hu YY, Gao XH, Zhou Y, Shen MN, Peng YF, Pan BS, Zhou J, Fan J, Yang XR, Guo W. Serum IgG4:IgG Ratio Predicts Recurrence of Patients with Hepatocellular Carcinoma after Curative Resection. J Cancer 2017; 8(8):1338-1346. doi:10.7150/jca.18030. Available from https://www.jcancer.org/v08p1338.htm

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Aim: IgG4 is associated with a Th1-to-Th2 switch, which plays a vital role in metastasis, in patients with malignances; thus, we aimed to investigate its clinical significance in predicting hepatocellular carcinoma (HCC) recurrence in the present study.

Methods: The correlation between serum IgG4:IgG ratio and recurrence was analyzed in a cohort of 195 patients undergoing curative resection in 2012. Another 100 patients were analyzed in a prospective independent cohort during 2012-2013 to validate the value of serum IgG4. Serum IgG4 and total IgG concentrations were measured with an automatic immune analyzer and the optimal cutoff value for serum IgG4 levels was determined by X-tile software.

Results: Our data revealed that serum IgG4:IgG were significantly elevated in patients with tumor recurrence (P<0.05). A cutoff IgG:IgG4 ratio of 0.08 was set to stratify HCC patients into high (>0.08) and low (≤0.08) groups. High serum IgG4:IgG ratio correlated with significantly shorter time-to-recurrence (median 11.85 months vs. 39.20, P=0.005). Univariate and multivariate analyses demonstrated that serum IgG4:IgG ratio is an independent indicator of tumor recurrence and this retained its clinical significance even in conventional low-recurrence-risk subgroups, including patients with low α-fetoprotein and early-stage diseases.

Conclusion: Our results demonstrated that elevated serum IgG4:IgG ratio is associated with poor clinical outcomes in HCC patients and therefore, and can serve as a novel prognostic predictor for HCC patients undergoing resection. Analyzing serum IgG4 would be useful to tailor individualized therapies for patients.

Keywords: Hepatocellular carcinoma, serum biomarkers, IgG4, recurrence, prognosis, curative resection, Th1-to-Th2 switch.