J Cancer 2019; 10(15):3333-3343. doi:10.7150/jca.29769

Research Paper

High GCLC level in tumor tissues is associated with poor prognosis of hepatocellular carcinoma after curative resection

Jialei Sun1,2,*, Chenhao Zhou2,3,*, Qianni Ma1,2,*, Wanyong Chen3,4, Manar Atyah3, Yirui Yin3, Peiyao Fu3, Shuang Liu3, Bo Hu3, Ning Ren3,4,✉, Haijun Zhou1,2,✉

1. Liver Cancer Institute & Zhongshan Hospital, Fudan University, Shanghai 200032, China
2. Key Laboratory of Carcinogenesis & Cancer Invasion, Ministry of Education, China
3. Department of Liver Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China
4. Department of Surgery, Institute of Fudan-Minhang Acadamic Health System, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai, China
* Equally contributed authors.

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Citation:
Sun J, Zhou C, Ma Q, Chen W, Atyah M, Yin Y, Fu P, Liu S, Hu B, Ren N, Zhou H. High GCLC level in tumor tissues is associated with poor prognosis of hepatocellular carcinoma after curative resection. J Cancer 2019; 10(15):3333-3343. doi:10.7150/jca.29769. Available from http://www.jcancer.org/v10p3333.htm

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Abstract

Glutamate-cysteine ligase catalytic subunit (GCLC) has been reported to overexpress in a variety types of cancer and be related with tumor progression and drug resistance. However, little has been known about GCLC's prognostic significance and biological roles in hepatocellular carcinoma (HCC). In the present study, we evaluated GCLC expression level using immunohistochemical staining (IHC) in tissue microarray (TMA) containing paired tumor and peritumoral liver tissues from 168 patients with HCC who received curative resection. GCLC levels in tumor tissues were significantly higher than in peritumoral liver tissues, and tumor GCLC level was associated with overall survival (OS) and disease-free survival (DFS). Five-year OS and DFS rates were 41.15% and 25.88% for the group with high tumor GCLC level, compared with 68.09% and 47.51% for the group with low tumor GCLC level (P<0.001 and P=0.001, respectively). Moreover, quantitative reverse transcription PCR (qRT-PCR) analysis demonstrated that GCLC was transcriptionally activated in HCC tissues when comparing with peritumoral tissues. Tumor GCLC level, which correlated to tumor differentiation, microvascular invasion and BCLC stage, was independent prognostic factors for both OS (P=0.006) and DFS (P=0.003). Importantly, tumor GCLC level was still significantly associated with OS and DFS in patients with early HCC. GCLC-based nomogram models were further established and exhibit significantly higher predictive accuracy as compared with routine clinical staging systems. In conclusion, tumor GCLC is a potential prognostic biomarker for HCC patients after receiving curative resection.

Keywords: GCLC, Hepatocellular carcinoma, Prognosis, Survival analysis, Nomogram