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World J Gastroenterol. Apr 28, 2014; 20(16): 4586-4596
Published online Apr 28, 2014. doi: 10.3748/wjg.v20.i16.4586
Inflammation-related factors predicting prognosis of gastric cancer
Wen-Jun Chang, Yan Du, Xin Zhao, Li-Ye Ma, Guang-Wen Cao
Wen-Jun Chang, Yan Du, Guang-Wen Cao, Department of Epidemiology, Second Military Medical University, Shanghai 200433, China
Xin Zhao, Li-Ye Ma, Department of General Surgery, Changhai Hospital, Second Military Medical University, Shanghai 200438, China
Author contributions: Chang WJ, Du Y and Zhao X collected data, drafted the manuscript and contributed equally to this work; Ma LY critically read this paper; Cao GW supervised and revised the manuscript.
Supported by National Natural Science Fund for China No. 81025015, No. 81372671 and No. 91129301
Correspondence to: Guang-Wen Cao, MD, PhD, Professor of Medicine, Chairman, Department of Epidemiology, Second Military Medical University, 800 Xiangyin Rd., Shanghai 200433, China. gcao@smmu.edu.cn
Telephone: +86-21-81871060 Fax: +86-21-81871060
Received: October 29, 2013
Revised: December 24, 2013
Accepted: January 20, 2014
Published online: April 28, 2014
Processing time: 182 Days and 1.2 Hours
Abstract

Gastric cancer (GC), which is mainly induced by Helicobacter pylori (H. pylori) infection, is one of the leading causes of cancer-related death in the developing world. Active inflammation initiated by H. pylori infection and maintained by inherent immune disorders promotes carcinogenesis and postoperative recurrence. However, the presence with H. pylori in tumors has been linked to a better prognosis, possibly due to the induction of antitumor immunity. Tumor infiltrations of tumor-associated macrophages, myeloid-derived suppressor cells, neutrophils, Foxp3+ regulatory T cells are correlated with poor prognosis. Tumor infiltrating CD8+ cytotoxic T lymphocytes, dendritic cells, and CD45RO T cells are generally associated with good prognosis of GC, although some subsets of these immune cells have inverse prognosis prediction values. High ratios of Foxp3+/CD4+ and Foxp3+/CD8+ in tumors are associated with a poor prognosis; whereas high Th1/Th2 ratio in tumors predicts a good prognosis. High levels of interleukin (IL)-6, IL-10, IL-32, and chemokine C-C motif ligands (CCL)7 and CCL21 in circulation, high expression of CXC chemokine receptor 4, chemokine C-C motif receptor (CCR)3, CCR4, CCR5, CCR7, hypoxia-inducible factor-1α, signal transducer activator of transcription-3, cyclooxygenase-2, and orphan nuclear receptor 4A2 in tumors are associated with an unfavorable prognosis. Increased serum levels of matrix metalloproteinases (MMP)-3, MMP-7, and MMP-11 and increased levels of MMP-9, MMP-12, and MMP-21 in tumors are consistently associated with poor survival of GC. Further emphasis should be put on the integration of these biomarkers and validation in large cohorts for personalized prediction of GC postoperative prognosis.

Keywords: Gastric cancer; Inflammation; Biomarker; Prognosis

Core tip: The prognosis of gastric cancer (GC) is not satisfactory, and is associated with Helicobacter pylori and/or Epstein-Barr virus infection, as well as host inflammation-related factors. In this article, we summarize the inflammation-related microbial and host factors that are reported to be associated with GC prognosis from different specimens and populations. So far, few simple panels have been clinically used for predicting GC prognosis. It is necessary to integrate different biomarkers with clinicopathological variables for personalized prediction of GC prognosis. The prognostic values of integrated predicators should be validated in large prospective cohorts before clinical application.