Abstract
Endoscopic surgery is increasingly used for early gastric cancer (EGC) treatment worldwide, and lymph node metastasis remains the most important risk factor for endoscopic surgery in EGC patients. Olfactomedin 4 (OLFM4) is mainly expressed in the digestive system and upregulated in several types of tumors. However, the role of OLFM4 in EGC has not been explored. We evaluated OLFM4 expression by immunohistochemical staining in 105 patients with EGC who underwent gastrectomy. The clinicopathological factors and OLFM4 expression were co-analyzed to predict lymph node metastasis in EGC. The metastatic mechanism of OLFM4 in gastric cancer was also investigated. We found that OLFM4 was upregulated in EGC tumor sections, and relatively low expression of OLFM4 was observed in patients with lymph node metastasis. OLFM4 expression as well as tumor size and differentiation were identified as independent factors, which could be co-analyzed to generate a better model for predicting lymph node metastasis in EGC patients. In vitro studies revealed that knockdown of OLFM4 promoted the migration of gastric cancer cells through activating the NF-κB/interleukin-8 axis. Negative correlation between OLFM4 and interleukin-8 expression was also observed in EGC tumor samples. Our study implies that OLFM4 expression is a potential predictor of lymph node metastasis in EGC, and combing OLFM4 with tumor size and differentiation could better stratify EGC patients with different risks of lymph node metastasis.
Highlights
Though the incidence and mortality have both declined over the past several decades, gastric cancer still ranks the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide.[1]
Results demonstrated that Olfactomedin 4 (OLFM4) was upregulated in early gastric cancer (EGC) tumor sections compared with adjacent non-tumor tissues (P o0.001), and was mainly distributed within the cytoplasm of the tumor cells (Figure 1a)
We found that in EGC patients with upregulation of OLFM4, the rate of lymph node metastasis (LNM) was 17.98% (16/89), while in patients with OLFM4 downregulation, the rate increased to 50.00% (8/16) (Figure 1a)
Summary
Though the incidence and mortality have both declined over the past several decades, gastric cancer still ranks the fifth most common malignancy and the third leading cause of cancer-related deaths worldwide.[1] Along with the improvement of diagnostic methods and public health awareness, the number of early gastric cancer (EGC) is rapidly growing. Because of the lower complication rate, improved quality of life and similar long-term outcome compared with gastrectomy, endoscopic surgery, including endoscopic mucosal resection and endoscopic submucosal dissection, have been proposed as a replacement for conventional surgery.[2] For more than a decade in the past, endoscopic surgery has gained increasing acceptance worldwide. As endoscopic surgery could not perform systemic lymph node sweeping, the presence of lymph node metastasis (LNM) is the most important risk factor for EGC patients. Though LNM of EGC is not common, it is still present in 3–5% of patients with mucosal cancer and
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