Assessment of Epinephrine and Norepinephrine in Gastric Carcinoma

Abstract

The aim of our study was to assess the sympathetic nervous system’s involvement in the evolution of gastric carcinoma in patients by analyzing the mediators of this system (epinephrine and norepinephrine), as well as by analyzing the histological expression of the norepinephrine transporter (NET). We conducted an observational study including 91 patients diagnosed with gastric carcinoma and an additional 200 patients without cancer between November 2017 and October 2018. We set the primary endpoint as mortality from any cause in the first two years after enrolment in the study. The patients were monitored by a 24-h Holter electrocardiogram (ECG) to assess sympathetic or parasympathetic predominance. Blood was also collected from the patients to measure plasma free metanephrine (Meta) and normetanephrine (N-Meta), and tumor histological samples were collected for the analysis of NET expression. All of this was performed prior to the application of any antineoplastic therapy. Each patient was monitored for two years. We found higher heart rates in patients with gastric carcinoma than those without cancer. Regarding Meta and N-Meta, elevated levels were recorded in the patients with gastric carcinoma, correlating with the degree of tumor differentiation and other negative prognostic factors such as tumor invasion, lymph node metastasis, and distant metastases. Elevated Meta and N-Meta was also associated with a poor survival rate. All these data suggest that the predominance of the sympathetic nervous system’s activity predicts increased gastric carcinoma severity.

Sympathetic Nervous Influences Are Negative Prognostic Factors in Stomach Cancer

“…Recent studies have shown that the sympathetic nervous system is involved in many types of cancer [21,[36][37][38][39]. This subdivision of the nervous system acts through noradrenaline, which is released by the local sympathetic fibers in the vicinity of or even inside the gastric tumors and through epinephrine released from the adrenal gland [21]. In this type of cancer, the most frequently expressed receptors are beta 2 adrenoreceptors [22].…”

“…Noradrenaline (NE) plays a key role in the advancement of gastric cancer, primarily through its interaction with beta adrenergic receptors and the subsequent activation of various signal transduction pathways. Norepinephrine (NE) can trigger epithelial-mesenchymal transition (EMT), which in turn promotes the invasion and metastasis of gastric cancer [21][22][23][24]. The beta adrenergic pathway is responsible for mediating the sympathetic nervous system (SNS) [25].…”

The Secretome of Parental and Bone Metastatic Breast Cancer Elicits Distinct Effects in Human Osteoclast Activity after Activation of β2 Adrenergic Signaling

“…Other players might have an important role in BC bone metastasis. Sympathetic nervous system (SNS) activity is often exacerbated in several types of cancer [ 8 , 9 ], and multiple pharmacological in vitro studies with human cells and murine ex vivo bone cultures have implicated the SNS in extravasation and colonization of the bone in prostate cancer [ 10 , 11 ]. The SNS is involved in the “fight or flight” response to stress and its main effector neurotransmitters are the catecholamines norepinephrine and epinephrine, which are released in sympathetic nerve terminals in target peripheral tissues or in the circulation by the adrenal gland, respectively [ 12 ].…”

Expression of M3 muscarinic acetylcholine receptors in gastric cancer

“…These disturbances are accentuated in the presence of chronic stress, through the increased serum levels of catecholamines and cortisol [ 11 ]. Also, the unfavorable evolution and the increased death rate in gastric cancer are correlated with high serum levels of catecholamine metabolites, metanephrine and normetanephrine, as well as with the increase in the number of norepinephrine transporter [ 12 ].…”