Glutamine Synthetase Predicts Adjuvant TACE Response in Hepatocellular Carcinoma

Overview

Journal Int J Clin Exp Med

Specialty General Medicine

Date 2016 Feb 18

PMID 26884995

Citations 2

Authors

Bo Zhang

Kai Liu

Jian Zhang

Liwei Dong

Zhichao Jin

Xinji Zhang

Feng Xue

Jia He

Affiliations

Soon will be listed here.

Abstract

Background: Adjuvant transcatheter arterial chemoembolization (TACE) is associated with better outcome and reduced tumor recurrence in hepatocellular carcinoma (HCC) patients. This study aimed to investigate the relationship between glutamine synthetase (GS) expression and survival of HCC patients after postoperative adjuvant TACE.

Methods: We retrospectively analyzed 554 HCC patients in two independent cohorts who underwent curative resection. Immunohistochemistry assay was used to investigate the expression of GS protein and evaluate the association with survival and the response to adjuvant TACE.

Results: In training cohort, patients with low GS expression who received postoperative adjuvant TACE showed a better overall survival (OS) (P<0.001) and less early phase recurrence (P=0.016). Adjuvant TACE was an independent prognostic factor for 5-year OS (HR=0.408, 95% CI 0.261-0.639, P<0.001) and early phase recurrence (HR=0.592, 95% CI 0.376-0.931, P=0.023). The same result was confirmed in validation cohort. Patients with high GS expression in both cohorts did not have a significant response to adjuvant TACE in OS and early phase recurrence.

Conclusions: GS status in tumor might be a useful tool in the selection of HCC patients who would be likely to benefit from postoperative adjuvant TACE.

Citing Articles

Glutamine metabolic reprogramming in hepatocellular carcinoma.

Ye Y, Yu B, Wang H, Yi F Front Mol Biosci. 2023; 10:1242059.

PMID: 37635935 PMC: 10452011. DOI: 10.3389/fmolb.2023.1242059.

Glutamine Metabolism Scoring Predicts Prognosis and Therapeutic Resistance in Hepatocellular Carcinoma.

Ying L, Cheng M, Lu Y, Tao Q, Chen X, Shen B Pathol Oncol Res. 2022; 27:1610075.

PMID: 34992505 PMC: 8724684. DOI: 10.3389/pore.2021.1610075.

References

Zhong C, Guo R, Li J, Shi M, Wei W, Chen M . A randomized controlled trial of hepatectomy with adjuvant transcatheter arterial chemoembolization versus hepatectomy alone for Stage III A hepatocellular carcinoma. J Cancer Res Clin Oncol. 2009; 135(10):1437-45. DOI: 10.1007/s00432-009-0588-2. View

Tremosini S, Forner A, Boix L, Vilana R, Bianchi L, Reig M . Prospective validation of an immunohistochemical panel (glypican 3, heat shock protein 70 and glutamine synthetase) in liver biopsies for diagnosis of very early hepatocellular carcinoma. Gut. 2012; 61(10):1481-7. DOI: 10.1136/gutjnl-2011-301862. View

Di Tommaso L, Franchi G, Park Y, Fiamengo B, Destro A, Morenghi E . Diagnostic value of HSP70, glypican 3, and glutamine synthetase in hepatocellular nodules in cirrhosis. Hepatology. 2007; 45(3):725-34. DOI: 10.1002/hep.21531. View

Cairns R, Harris I, Mak T . Regulation of cancer cell metabolism. Nat Rev Cancer. 2011; 11(2):85-95. DOI: 10.1038/nrc2981. View

Cheng H, Wang X, Chen D, Xu A, Jia Y . The value and limitation of transcatheter arterial chemoembolization in preventing recurrence of resected hepatocellular carcinoma. World J Gastroenterol. 2005; 11(23):3644-6. PMC: 4315980. DOI: 10.3748/wjg.v11.i23.3644. View

Bruix J, Llovet J . Prognostic prediction and treatment strategy in hepatocellular carcinoma. Hepatology. 2002; 35(3):519-24. DOI: 10.1053/jhep.2002.32089. View

Choi G, Kim D, Kang C, Kim K, Choi J, Lee W . Prognostic factors and optimal treatment strategy for intrahepatic nodular recurrence after curative resection of hepatocellular carcinoma. Ann Surg Oncol. 2007; 15(2):618-29. DOI: 10.1245/s10434-007-9671-6. View

Lai E, Lo C, Fan S, Liu C, Wong J . Postoperative adjuvant chemotherapy after curative resection of hepatocellular carcinoma: a randomized controlled trial. Arch Surg. 1998; 133(2):183-8. DOI: 10.1001/archsurg.133.2.183. View

van der Hel W, Notenboom R, Bos I, van Rijen P, van Veelen C, De Graan P . Reduced glutamine synthetase in hippocampal areas with neuron loss in temporal lobe epilepsy. Neurology. 2005; 64(2):326-33. DOI: 10.1212/01.WNL.0000149636.44660.99. View

10.

Allegra C, Jessup J, Somerfield M, Hamilton S, Hammond E, Hayes D . American Society of Clinical Oncology provisional clinical opinion: testing for KRAS gene mutations in patients with metastatic colorectal carcinoma to predict response to anti-epidermal growth factor receptor monoclonal antibody therapy. J Clin Oncol. 2009; 27(12):2091-6. DOI: 10.1200/JCO.2009.21.9170. View

11.

Wang K, Liu J, Yan Z, Li J, Shi L, Cong W . Overexpression of aspartyl-(asparaginyl)-beta-hydroxylase in hepatocellular carcinoma is associated with worse surgical outcome. Hepatology. 2010; 52(1):164-73. DOI: 10.1002/hep.23650. View

12.

Audard V, Cavard C, Richa H, Infante M, Couvelard A, Sauvanet A . Impaired E-cadherin expression and glutamine synthetase overexpression in solid pseudopapillary neoplasm of the pancreas. Pancreas. 2008; 36(1):80-3. DOI: 10.1097/mpa.0b013e318137a9da. View

13.

Rosati A, Poliani P, Todeschini A, Cominelli M, Medicina D, Cenzato M . Glutamine synthetase expression as a valuable marker of epilepsy and longer survival in newly diagnosed glioblastoma multiforme. Neuro Oncol. 2013; 15(5):618-25. PMC: 3635515. DOI: 10.1093/neuonc/nos338. View

14.

Imamura H, Matsuyama Y, Tanaka E, Ohkubo T, Hasegawa K, Miyagawa S . Risk factors contributing to early and late phase intrahepatic recurrence of hepatocellular carcinoma after hepatectomy. J Hepatol. 2003; 38(2):200-7. DOI: 10.1016/s0168-8278(02)00360-4. View

15.

Dal Bello B, Rosa L, Campanini N, Tinelli C, Torello Viera F, DAmbrosio G . Glutamine synthetase immunostaining correlates with pathologic features of hepatocellular carcinoma and better survival after radiofrequency thermal ablation. Clin Cancer Res. 2010; 16(7):2157-66. DOI: 10.1158/1078-0432.CCR-09-1978. View

16.

Ji J, Shi J, Budhu A, Yu Z, Forgues M, Roessler S . MicroRNA expression, survival, and response to interferon in liver cancer. N Engl J Med. 2009; 361(15):1437-47. PMC: 2786938. DOI: 10.1056/NEJMoa0901282. View

17.

Poon R, Fan S, Lo C, Liu C, Wong J . Intrahepatic recurrence after curative resection of hepatocellular carcinoma: long-term results of treatment and prognostic factors. Ann Surg. 1999; 229(2):216-22. PMC: 1191634. DOI: 10.1097/00000658-199902000-00009. View

18.

Zhang B, Dong L, Tan Y, Zhang J, Pan Y, Yang C . Asparagine synthetase is an independent predictor of surgical survival and a potential therapeutic target in hepatocellular carcinoma. Br J Cancer. 2013; 109(1):14-23. PMC: 3708586. DOI: 10.1038/bjc.2013.293. View

19.

Shin E, Ryu H, Kim S, Jung H, Jang J, Lee K . The clinicopathological significance of heat shock protein 70 and glutamine synthetase expression in hepatocellular carcinoma. J Hepatobiliary Pancreat Sci. 2011; 18(4):544-50. DOI: 10.1007/s00534-010-0367-0. View

20.

Chapman P, Hauschild A, Robert C, Haanen J, Ascierto P, Larkin J . Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N Engl J Med. 2011; 364(26):2507-16. PMC: 3549296. DOI: 10.1056/NEJMoa1103782. View