Jiafei Lin1, Yingwei Zhang2, Jiemin Wu3, Li Li3, Ning Chen3, Peihua Ni3, Lihua Song4, Xiangfan Liu5. 1. Department of Clinical Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China. 2. Nanjing Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing 210008, PR China. 3. Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China. 4. School of Agriculture & Biology, Shanghai Jiaotong University, Shanghai 200240, PR China. Electronic address: songlihua2018@126.com. 5. Department of Laboratory Medicine, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, PR China. Electronic address: liuxiangfan1976@163.com.
Abstract
BACKGROUND: TEA domain transcription factor (TEAD) has an oncogenic role in hepatocellular carcinoma (HCC). However, whether a membrane protein can serve not only as a tumor marker that reflects TEAD function but also as a therapeutic target that stimulates tumorigenesis in HCC remains unknown. METHODS: Tissue NRP1 was measured using immunohistochemistry. Cell viability, colony formation and caspase3/7 activity were assessed using MTT, soft agar and caspase 3/7 Glo assays, respectively. Serum NRP1 was examined using ELISA and Western blotting. RESULTS: NRP1 expression was up-regulated by TEAD. We also identified a conserved TEAD-binding motif in the NRP1 promoters, which was essential for the TEAD-NRP1 interaction. NRP1 was upregulated in HCC tissues and cell lines, and knockdown of NRP1 inhibited the transformative phenotypes of HCC cells. Notably, the concentrations of serum NRP1 in the HCC patients were much higher than those of hepatitis B, hepatitis C, cirrhosis, breast cancer, colon cancer, gastric cancer and lung cancer patients. Moreover, serum NRP1 was significantly associated with AFP, γ-GT, Alb, bile acid, ALT, AST, ALP and pre-Alb. The area under the receiver operating characteristic curve (AUC-ROC) for serum NRP1 was 0.971, presenting better diagnostic performance compared to AFP. CONCLUSIONS: NRP1 is a novel tumor marker in HCC.
BACKGROUND: TEA domain transcription factor (TEAD) has an oncogenic role in hepatocellular carcinoma (HCC). However, whether a membrane protein can serve not only as a tumor marker that reflects TEAD function but also as a therapeutic target that stimulates tumorigenesis in HCC remains unknown. METHODS: Tissue NRP1 was measured using immunohistochemistry. Cell viability, colony formation and caspase3/7 activity were assessed using MTT, soft agar and caspase 3/7 Glo assays, respectively. Serum NRP1 was examined using ELISA and Western blotting. RESULTS:NRP1 expression was up-regulated by TEAD. We also identified a conserved TEAD-binding motif in the NRP1 promoters, which was essential for the TEAD-NRP1 interaction. NRP1 was upregulated in HCC tissues and cell lines, and knockdown of NRP1 inhibited the transformative phenotypes of HCC cells. Notably, the concentrations of serum NRP1 in the HCC patients were much higher than those of hepatitis B, hepatitis C, cirrhosis, breast cancer, colon cancer, gastric cancer and lung cancerpatients. Moreover, serum NRP1 was significantly associated with AFP, γ-GT, Alb, bile acid, ALT, AST, ALP and pre-Alb. The area under the receiver operating characteristic curve (AUC-ROC) for serum NRP1 was 0.971, presenting better diagnostic performance compared to AFP. CONCLUSIONS:NRP1 is a novel tumor marker in HCC.
Authors: Esperanza Gonzalez; Mikel Azkargorta; Clara Garcia-Vallicrosa; Janire Prieto-Elordui; Felix Elortza; Sonia Blanco-Sampascual; Juan Manuel Falcon-Perez Journal: Int J Biol Sci Date: 2021-05-05 Impact factor: 6.580