CXC chemokine receptor 1 predicts postoperative prognosis and chemotherapeutic benefits for TNM II and III resectable gastric cancer patients

Oncotarget. 2017 Mar 21;8(12):20328-20339. doi: 10.18632/oncotarget.12815.

Abstract

Backround: Abnormal expression of CXC chemokine receptor 1 (CXCR1) has shown the ability to promote tumor angiogensis, invasion and metastasis in several cancers. The purpose of our curret study is to discover the clinical prognostic significance of CXCR1 in resectable gastric cancer.

Methods: 330 gastric cancer patients who underwent R0 gastrectomy with standard D2 lymphadenectomy at Zhongshan Hospital, Fudan University between 2007 and 2008 were enrolled. CXCR1 expression was evaluated with use of immunohistochemical staining. The relation between CXCR1 expression and clinicopathological features and postoperative prognosis was respectively inspected.

Results: In both discovery and validation data sets, CXCR1 high expression indicated poorer overall survival (OS) in TNM II and III patients. Furthermore, multivariate analysis identified CXCR1 expression and TNM stage as two independent prognostic factors for OS. Incorporating CXCR1 expression into current TNM staging system could generate a novel clinical predictive model for gastric cancer, showing better prognostic accuracy with respect to patients' OS. More importantly, TNM II patients with higher CXCR1 expression were shown to significantly benefit from postoperative 5-fluorouracil (5-FU) based adjuvant chemotherapy (ACT).

Conclusion: CXCR1 in gastric cancer was identified as an independent adverse prognostic factor. Combining CXCR1 expression with current TNM staging system could lead to better risk stratification and more accurate prognosis for gastric cancer patients. High expression of CXCR1 identified a subgroup of TNM stage II gastric cancer patients who appeared to benefit from 5-FU based ACT.

Keywords: CXCR1; adjuvant chemotherapy; gastric cancer; nomogram; overall survival.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage
  • Biomarkers, Tumor / analysis*
  • Chemotherapy, Adjuvant
  • Female
  • Fluorouracil / administration & dosage
  • Gastrectomy
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Postoperative Period
  • Prognosis
  • Receptors, Interleukin-8A / analysis
  • Receptors, Interleukin-8A / metabolism*
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology*
  • Stomach Neoplasms / therapy*
  • Tissue Array Analysis

Substances

  • Biomarkers, Tumor
  • Receptors, Interleukin-8A
  • Fluorouracil