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

Abstract

Background:NOS3 (endothelial NOS, eNOS) is a member of the nitric oxide synthase (NOS) enzyme family, mainly participating in nitric oxide (NO) generation. NOS3 has been reported to inhibit apoptosis and promote angiogenesis, proliferation, and invasiveness. However, the expression pattern of NOS3 and its diagnostic and prognostic potential has not been investigated in a pan-cancer perspective.Methods: 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 NOS3 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 NOS3 in gastric cancer patients. GSVA and GSEA analyses were performed to investigate signaling pathways related to NOS3 expression.Results: In normal tissues, NOS3 was expressed highest in the spleen and lowest in the blood. NOS3 expression was increased in stomach adenocarcinoma (STAD) and significantly associated with poor prognosis of patients. Immunohistochemical staining validated that NOS3 was an independent prognostic factor of gastric cancer. Several canonical cancer-related pathways were found to be correlated with NOS3 expression in STAD. The expression of NOS3 was related to the response to QS-11 and brivinib in STAD.Conclusions:NOS3 was an independent prognostic factor for patients with STAD. Increased expression of NOS3 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.

LINC00887 Fosters Development of Clear Cell Renal Cell Carcinoma via Inhibiting CD8+ T Cell Immune Infiltration

“…The results suggested that the oncogenic effect of LINC00887 may be associated with a higher PBRM1 mutation level. Also, NOS3 was reported to serve as an oncogene in gastric cancer [ 36 ], which supports the predicted result on the expression relationship between LINC00887 and NOS3 in this study In a word, the expression trend of LINC00887 is relatively consistent with that of most immunosuppressive genes. This further confirmed that LINC00887 was involved in the immunosuppressive regulation of ccRCC and promoted malignant progression of ccRCC through synergistic expression of immunosuppressive molecules.…”

“…The results suggested that the oncogenic effect of LINC00887 may be associated with a higher PBRM1 mutation level. Also, NOS3 was reported to serve as an oncogene in gastric cancer [36], which supports the predicted result on the expression relationship between LINC00887 and NOS3 in this study In a word, the expression trend of LINC00887 is relatively consistent with that of most immunosuppressive genes. This further confirmed that LINC00887 was involved In conclusion, this study preliminarily illustrated the high level of LINC00887 in ccRCC, and it was negatively connected to the abundance of CD8+ T cell immune infiltration; LINC00887 knockdown led to increased cytotoxicity, weakened apoptosis ability, and enhanced chemotactic ability of CD8+ T cells.…”

Drug metabolism‐related eight‐gene signature can predict the prognosis of gastric adenocarcinoma

“…A pan-cancer analysis found that increased NOS3 expression in gastric adenocarcinoma may lead to poor prognosis through several typical cancer-related pathways. 39 This finding is consistent with our results; however, how NOS3 influences gastric adenocarcinoma prognosis through cancer-related pathways requires investigation.…”

Mechanisms of Cannabidiol (CBD) in Cancer Treatment: A Review

“…In oxaliplatin-resistant DLD-1 and colo205 cell lines, CBD (4 µM) induced autophagic cell death by decreasing nitric oxide synthase 3 (NOS3) activity and the activation of the AMP-activated protein kinase (AMPK), TOR, and Akt signaling pathways [ 48 ], all of which are key signaling proteins involved in tumorigenesis [ 72 ]. NOS3 mainly participates in the generation of nitric oxide (NO) and has been found to promote the proliferation, angiogenesis, and invasiveness, as well as suppress the apoptosis, of cancer cells [ 73 ]. ROS and the autophagic markers, LC3 and p62, were increased by CBD via antioxidant SOD2, causing mitochondrial dysfunction [ 48 ].…”