Abstract
Gastric cancer is one of the most common malignancies worldwide. However, genetic alterations leading to this disease are largely unknown. Gene amplification is one of the most frequent genetic alterations, which is believed to play a major role in the development and progression of gastric cancer. In the present study, we identified three frequently amplified genes from 30 candidate genes using real-time quantitative PCR method, including ERBB4, C-MET and CD44, and further explored their association with clinicopathological characteristics and poor survival in a cohort of gastric cancers. Our data showed amplification of these genes was significantly associated with certain clinicopathological characteristics, particularly tumor differentiation and cancer-related death. More importantly, amplification of these genes was significantly related to worse survival, suggesting that these amplified genes may be significant predictors of poor prognosis and potential therapeutic targets in gastric cancer. Targeting these genes may thus provide new possibilities in the treatment of gastric cancer.
Highlights
Gastric cancer is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide [1]
With a gene copy number of 4 or more defined as gene amplification, we found that ERBB4, C-MET and CD44 genes were frequently amplified in gastric cancers, other genes were not or infrequently amplified in gastric cancers, ranging from 0 to 8%
The data showed that the prevalence of amplification of ERBB4, C-MET and CD44 was 67% (86/128), 30% (39/128) and 66% (84/128), respectively, but not in the normal gastric tissues
Summary
Gastric cancer is one of the most common malignancies and remains the second leading cause of cancer-related death worldwide [1]. Recent diagnostic and therapeutic advances have gradually improved clinical outcome of the patients with early gastric cancer, gastric cancer is usually diagnosed at an advanced stage and the prognosis is still poor [3], reflecting limited advances in our understanding of the pathogenesis of this disease. A better understanding of the molecular mechanisms and genetic alterations of gastric cancer may lead to new diagnostic and therapeutic strategies to this disease. Like other types of genetic alterations, gene amplification reflects the genetic instability of the tumor cells, and may confer diagnostic, prognostic, or therapeutic information for patient management [8]
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