Weiyou Zhu1,2, Ling Ma1, Jing Qian1, Jin Xu3, Tongpeng Xu1, Lijun Pang2, Hong Zhou2, Yongqian Shu1,4, Jianwei Zhou3,4. 1. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University Nanjing 210029, People's Republic of China. 2. Cancer Center, The Affiliated Jiangsu Shengze Hospital of Nanjing Medical University Suzhou 215228, People's Republic of China. 3. Department of Molecular Cell Biology and Toxicology, Cancer Center, School of Public Health, Nanjing Medical University 101 Longmian Avenue, Nanjing 211166, Jiangsu Province, People's Republic of China. 4. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, Nanjing Medical University 101 Longmian Avenue, Nanjing 211166, People's Republic of China.
Abstract
OBJECTIVE: The use of human epidermal growth factor receptor-2 (HER2) as a biomarker for gastric cancer (GC) has greatly helped some patients receive benefit from HER2-targeted therapy. However, the correlation between HER2 and other biochemical markers is unclear. The aim of this study was to examine the relationship between HER2 and lactate dehydrogenase A (LDHA) in GC tissues and GC cells. METHODS: The correlation between clinicopathological features and HER2 was analyzed in 179 cases of GC. The expression of HER2 and LDHA was examined by immunohistochemical staining in 12 pairs of GC tissues and by western blotting in seven pairs of fresh GC tissues and adjacent normal tissues. Wound healing, transwell migration assay, quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR), and LDH activity assays were performed with GC cells. RESULTS: HER2 expression and serum LDH levels were closely correlated (P = 0.027) in 179 GC patient cases. Immunohistochemical staining demonstrated a positive correlation between HER2 and LDHA in 12 pairs of GC tissues (P = 0.0308). Knocking down LDHA suppressed cell migration and invasion in GC cells. In addition, HER2 positively regulated hypoxia-inducible factor-1α (HIF-1α) and LDHA. Furthermore, the expressions of HER2, HIF-1α, and LDHA were consistent in 5/7 pairs of fresh GC tissues and adjacent normal tissues as well as in GC cell lines. CONCLUSIONS: The HER2-HIF-1α-LDHA axis may serve as the basis for new methods and strategies for the treatment of GC.
OBJECTIVE: The use of human epidermal growth factor receptor-2 (HER2) as a biomarker for gastric cancer (GC) has greatly helped some patients receive benefit from HER2-targeted therapy. However, the correlation between HER2 and other biochemical markers is unclear. The aim of this study was to examine the relationship between HER2 and lactate dehydrogenase A (LDHA) in GC tissues and GC cells. METHODS: The correlation between clinicopathological features and HER2 was analyzed in 179 cases of GC. The expression of HER2 and LDHA was examined by immunohistochemical staining in 12 pairs of GC tissues and by western blotting in seven pairs of fresh GC tissues and adjacent normal tissues. Wound healing, transwell migration assay, quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR), and LDH activity assays were performed with GC cells. RESULTS:HER2 expression and serum LDH levels were closely correlated (P = 0.027) in 179 GC patient cases. Immunohistochemical staining demonstrated a positive correlation between HER2 and LDHA in 12 pairs of GC tissues (P = 0.0308). Knocking down LDHA suppressed cell migration and invasion in GC cells. In addition, HER2 positively regulated hypoxia-inducible factor-1α (HIF-1α) and LDHA. Furthermore, the expressions of HER2, HIF-1α, and LDHA were consistent in 5/7 pairs of fresh GC tissues and adjacent normal tissues as well as in GC cell lines. CONCLUSIONS: The HER2-HIF-1α-LDHA axis may serve as the basis for new methods and strategies for the treatment of GC.
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