Expression of Helios in gastric tumor cells predicts better survival in gastric cancer patients

Abstract

Purpose: Helios belongs to Ikaros family, which plays an important role in the cell-fate decision and control cell proliferation; abnormal expressions in leukemia are associated with poor prognosis. In this study, we investigated the Helios expression between Helicobacter pylori infection and prognosis in gastric cancer patients.

Methods: A total of 67 gastric cancer patients who received partial or full gastrectomies were enrolled. Helios expression by immunohistochemistry and mRNA was investigated with the clinical stage, Helicobacter pylori infection, CD4 expression, FoxP3 expression and prognosis.

Results: From the immunohistochemistry stain, we found that the Helios was expressed in both cancer cell and tumor-infiltrated lymphocytes. The high expression of Helios in gastric tumor cells had a better median overall survival rate in gastric cancer patients (50.7 ± 3.2 vs. 34.1 ± 4.9 months; P = 0.015), Helicobacter pylori-infected patients (51.1 ± 3.5 vs. 30.4 ± 5.1 months; P = 0.007) and advanced gastric cancer patients (42.1 ± 5.5 vs. 23.2 ± 4.8 months; P = 0.043). From multivariate analysis, the Helios expression in gastric tumor cells was an independent factor to predict better survival in all gastric cancers (HR = 2.78; 95 % confidence interval [CI], 1.09-7.09; P = 0.032) and advanced gastric cancer patients (HR = 2.85; 95 % confidence interval [CI], 1.00-8.13; P = 0.03).

Conclusions: Higher expression of Helios in gastric tumor cells predicts better survival in gastric cancer patients, especially for Helicobacter pylori-infected and advanced-stage gastric cancer patients.

Keywords: Gastric cancer; Helicobacter pylori; Helios; Prognosis.

Fig. 1

Immunohistochemical stains and the RNA expressions in gastric tumor. a Representative immunohistochemical staining of the infiltrated lymphocytes was stained with anti-Helios antibody (arrow). b Immunohistochemical staining of Helios (nuclear, brown color, white arrow) and Foxp3 (green color, arrow head) in infiltrated lymphocytes was indicated. The Helios expression (brown) was both detected in gastric tumor (c) and adjacent normal (d). e The Helios mRNA levels were determined by real-time PCR. f The IHC score of Helios expression in tumor and adjacent normal tissue from gastric tumor patients. Scale bar in a, c, d is 50 uM, and in b is 10 uM

Fig. 2

Kaplan–Meier curves and log-rank test results for the overall survival of the patients with gastric cancer based on the expression of Helios in tumor tissues. a Kaplan–Meier curves of overall survival of gastric cancer patients obtained by the expression of Helios. The test resulted in a P value of <0.05. b Kaplan–Meier curves of overall survival of HP-positive gastric cancer patients obtained by the expression of Helios. The test resulted in a P value <0.01. c Kaplan–Meier curves of overall survival of HP-negative gastric cancer patients obtained by the expression of Helios. It did not show significant differences

Fig. 3

Kaplan–Meier curves and log-rank test results for the overall survival of the patients with advanced gastric cancer based on the expression of Helios in tumor tissues. a Kaplan–Meier curves of overall survival of advanced-stage (T3+T4) gastric cancer patients obtained by the expression of Helios. The test resulted in a P value <0.05. b Kaplan–Meier curves of overall survival of lower-stage (T1+T2) gastric cancer patients obtained by the expression of Helios. It did not show significant differences