Abstract
BackgroundGastric cancer is the eighth most common cancer in Taiwan, with a 40% 5-year survival rate. Approximately 40% of patients are refractory to chemotherapy. Currently, the anti-HER2 therapy is the only clinically employed targeted therapy. However, only 7% patients in Taiwan are HER2-positive. Identifying candidate target genes will facilitate the development of adjuvant targeted therapy to increase the efficacy of gastric cancer treatment.MethodsClinical specimens were analyzed by targeted RNA sequencing to assess the expression levels of target genes. Statistical significance of differential expression and correlation between specimens was evaluated. The correlation with patient survival was analyzed as well. In vitro cell mobility was determined using wound-healing and transwell mobility assays.ResultsExpression of BMP1, COL1A1, STAT3, SOX2, FOXA2, and GATA6 was progressively dysregulated through the stages of gastric oncogenesis. The expression profile of these six genes forms an ubiquitously biomarker signature that is sufficient to differentiate cancer from non-cancerous specimens. High expression status of BMP1 correlates with poor long-term survival of late-stage patients. In vitro, suppression of BMP1 inhibits the mobility of the gastric cancer cell lines, indicating a role of BMP1 in metastasis.ConclusionsBMP1 is upregulated in gastric cancer and is correlated with poor patient survival. Suppression of BMP1 reduced gastric cancer mobility in vitro. Our finding suggests that anti-BMP1 therapy will likely augment the efficacy of standard chemotherapy and improve the treatment outcome.
Highlights
Gastric cancer is the eighth most common cancer in Taiwan, with a 40% 5-year survival rate
We found the highest level of collagen 1A1 (COL1A1) as well as the lowest level of GATA-binding factor 6 (GATA6) and SRY-bo× 2 (SOX2), suggesting a strong correlation between the expression levels of these genes
The efficacy of chemotherapy can be greatly improved by administration of adjuvant targeted therapy, only anti-HER2 therapy is currently being used for gastric cancer treatment in Taiwan
Summary
Gastric cancer is the eighth most common cancer in Taiwan, with a 40% 5-year survival rate. Besides Helicobacter pylori (Hp) infection [2, 3], additional environmental and habitual factors, such as consumption of high-salt and fermented dietary products and smoking, are associated with an increase of the risk for gastric cancer [4, 5]. Due to these diverse lifestyle-dependent risk factors, it is likely that the underlying oncogenic molecular mechanisms of gastric cancer display distinct biomarker signatures unique to different cultural populations
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