Abstract
Gastric cancer is one of the most common cancers worldwide and is the third leading cause of cancer-related deaths globally. Although significant progress has been made in the diagnosis and treatment for the cancer, less improvement has been made in overall survival rate. Thus, there is an urgent need for a better understanding of the biological aspects of the cancer. The transcription factor transcription factor 7-like 1 (TCF7L1) is an embryonic stem cell signature gene that is upregulated in multiple aggressive cancer types, but its role in gastric cancer has seldom been discussed. In the present study, by using the Cancer Genome Atlas dataset analysis, we demonstrated that patients with higher expression of TCF7L1 could be used to reflect prognosis. An examination of the mechanisms demonstrated that TCF7L1 could positively regulate antioxidant response in gastric cancer cells by positively regulating Keap1/NRF2 [Kelch-like ECH-associated protein 1/nuclear factor (erythroid-derived 2)-like 2] pathway. Collectively, our data demonstrated that TCF7L1 is a novel marker for predicting overall survival of gastric cancer and provided the possible underlying molecular mechanism.
Highlights
Gastric cancer is one of the leading causes of mortality from neoplastic disease and is prevalent in Asian populations [1,2]
We explored the novel functions of transcription factor 7-like 1 (TCF7L1) in gastric cancer prognosis
Our results demonstrated that TCF7L1 promoted gastric cancer cell proliferation by positively regulating aerobic glycolysis and antioxidant response via NRF2, an important player in oncogenesis and progression in many types of cancers
Summary
Gastric cancer is one of the leading causes of mortality from neoplastic disease and is prevalent in Asian populations [1,2]. Detections and diagnosis of gastric cancer through endoscopic methods and subsequent treatment by submucosal resection has achieved a 5-year survival rate of up to 95% in cohort studies. Previous studies demonstrated that by comparing the expression profiles of signature genes in several types of poorly differentiated and aggressive tumors to those of embryonic stem (ES) cells, a subset of ES-specific transcriptional regulators was highly enriched. One such transcriptional regulator was transcription factor transcription factor 7-like 1 (TCF7L1, known as TCF3) [6,7,8].
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