OLFM4 is associated with lymph node metastasis and poor prognosis in patients with gastric cancer

Abstract

Purpose: The present study investigated the clinical significance of the relationship between olfactomedin 4 (OLFM4) expression and the clinicopathological features of patients with gastric cancer.

Methods: Tumor tissue and adjacent normal tissue, lymph nodes, and peritoneal metastases were analyzed by the Affymetrix GeneChip(®) HG-U133A2.0 array. The expression of OLFM4 was detected by real-time quantitative RT-PCR in gastric tumor tissue and adjacent normal tissue. OLFM4 expression was analyzed by immunohistochemistry in 436 clinicopathologically characterized gastric cancer cases and in corresponding distant metastases from 61 patients.

Results: A total of 434 genes and 169 expressed sequence tags were upregulated, including OLFM4. The expression of OLFM4 mRNA or protein differed significantly among gastric tumor tissue, matched normal gastric mucosa, and lymph node metastases. Further multivariate analysis suggested that lymph node metastases and distant metastases, TNM stage, and expression of OLFM4 were independent prognostic indicators for gastric cancer.

Conclusion: Gene expression profiles were useful for simultaneously analyzing the expression levels of thousands of genes. Reduced expression of OLFM4 in gastric cancer is associated significantly with lymph node and distant metastases and with poor prognosis. OLFM4 may prove to be an important molecular marker for predicting the carcinogenesis, development, progression, and metastasis of gastric cancer.

Fig. 1

Relative expression of OLFM4 in the corresponding gastric tumors compared with that in non-tumor tissues

Fig. 2

Immunohistochemical staining for OLFM4 in gastric cancer lesions and non-cancerous tissues. A1–A3 OLFM4 negative in non-cancerous tissues; magnifications were ×40, ×100, and ×400, respectively. B1–B3 OLFM4 was highly expressed in poorly differentiated adenocarcinoma; magnifications were ×40, ×100, and ×400, respectively. C1–C3 OLFM4 was highly expressed in moderately differentiated adenocarcinoma; magnifications were ×40, ×100, and ×400, respectively. D1–D3 OLFM4 was highly expressed in well-differentiated adenocarcinoma; magnifications were ×40, ×100, and ×400, respectively. E1–E3 OLFM4 was highly expressed in papillary adenocarcinoma; magnifications were ×40, ×100, and ×400, respectively

Fig. 3

a Kaplan–Meier curves with univariate analyses (log rank) for patients with high OLFM4 expression versus low OLFM4 expression tumors in stage I. The cumulative 5-year survival rate was 94.7% in the group with high expression but was only 75.0% in the low OLFM4 protein expression group (P = 0.033). b Kaplan–Meier curves with univariate analyses (log rank) for patients with high OLFM4 expression versus low OLFM4 expression tumors in stage II. The cumulative 5-year survival rate was 73.7% in the group with high expression but was only 64.0% in the low OLFM4 protein expression group (P = 0.017)

Fig. 4

a Kaplan–Meier curves with univariate analyses (log rank) for patients with high OLFM4 expression versus low OLFM4 expression tumors in T1 stage. The cumulative 5-year survival rate was 85.0% in the group with high expression but was only 58.8% in the low OLFM4 protein expression group (P = 0.045). b Kaplan–Meier curves with univariate analyses (log rank) for patients with high OLFM4 expression versus low OLFM4 expression tumors in T2 stage. The cumulative 5-year survival rate was 73.8% in the group with high expression but was only 46.3% in the low OLFM4 protein expression group (P = 0.003). c Kaplan–Meier curves with univariate analyses (log rank) for patients with high OLFM4 expression versus low OLFM4 expression tumors in T3 stage. The cumulative 5-year survival rate was 47.4% in the group with high expression but was only 25.7% in the low OLFM4 protein expression group (P = 0.003)

Fig. 5

Kaplan–Meier curves with univariate analyses (log rank) for patients with high OLFM4 expression versus low OLFM4 expression tumors in the group of lymph node-positive patients. The cumulative 5-year survival rate was 39.1% in the group with high expression but was only 17.5% in the low OLFM4 protein expression group (P = 0.007)