AUTHOR=Zou Dan , Li Zhi , Lv Fei , Yang Yi , Yang Chunjiao , Song Jincheng , Chen Yang , Jin Zi , Zhou Jinpeng , Jiang Yang , Ma Yanju , Jing Zhitao , Tang Yu , Zhang Ye 

TITLE=Pan-Cancer Analysis of NOS3 Identifies Its Expression and Clinical Relevance in Gastric Cancer

JOURNAL=Frontiers in Oncology

VOLUME=11

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2021.592761

DOI=10.3389/fonc.2021.592761

ISSN=2234-943X

ABSTRACT=<p><bold>Background:</bold><italic>NOS3</italic> (endothelial NOS, <italic>eNOS</italic>) is a member of the nitric oxide synthase (NOS) enzyme family, mainly participating in nitric oxide (NO) generation. <italic>NOS3</italic> has been reported to inhibit apoptosis and promote angiogenesis, proliferation, and invasiveness. However, the expression pattern of <italic>NOS3</italic> and its diagnostic and prognostic potential has not been investigated in a pan-cancer perspective.</p><p><bold>Methods:</bold> Data from the Genotype-Tissue Expression (GTEx), the Cancer Genome Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE), and the Cancer Therapeutics Response Portal (CTRP) were employed and <italic>NOS3</italic> expression was comprehensively analyzed in normal tissues, cancer tissues, and cell lines. Immunohistochemical staining of tissue sections were used to validate the prognostic role of <italic>NOS3</italic> in gastric cancer patients. GSVA and GSEA analyses were performed to investigate signaling pathways related to <italic>NOS3</italic> expression.</p><p><bold>Results:</bold> In normal tissues, <italic>NOS3</italic> was expressed highest in the spleen and lowest in the blood. <italic>NOS3</italic> expression was increased in stomach adenocarcinoma (STAD) and significantly associated with poor prognosis of patients. Immunohistochemical staining validated that <italic>NOS3</italic> was an independent prognostic factor of gastric cancer. Several canonical cancer-related pathways were found to be correlated with <italic>NOS3</italic> expression in STAD. The expression of NOS3 was related to the response to QS-11 and brivinib in STAD.</p><p><bold>Conclusions:</bold><italic>NOS3</italic> was an independent prognostic factor for patients with STAD. Increased expression of <italic>NOS3</italic> influenced occurrence and development of STAD through several canonical cancer-related pathways. Drug response analysis reported drugs to suppress NOS3. NOS3 might be a novel target for gastric cancer treatment.</p>