The Nervous System Contributes to the Tumorigenesis and Progression of Human Digestive Tract Cancer

Abstract

Tumors of the gastrointestinal tract are one of the highest incidences of morbidity and mortality in humans. Recently, a growing number of researchers have indicated that nerve fibers and nerve signals participate in tumorigenesis. The current overarching view based on the responses to therapy revealed that tumors are partly promoted by the tumor microenvironment (TME), endogenous oncogenic factors, and complex systemic processes. Homeostasis of the neuroendocrine-immune axis (NEI axis) maintains a healthy in vivo environment in humans, and dysfunction of the axis contributes to various cancers, including the digestive tract. Interestingly, nerves might promote tumor development via multiple mechanisms, including perineural invasion (PNI), central level regulation, NEI axis effect, and neurotransmitter induction. This review focuses on the association between digestive tumors and nerve regulation, including PNI, the NEI axis, stress, and neurotransmitters, as well as on the potential clinical application of neurotherapy, aiming to provide a new perspective on the management of digestive cancers.

Nestin Expression and the Survival of Patients With Digestive Tract Cancers: A Systematic Review and Meta-Analysis

“…Eleven studies 25 , 27 - 31 , 33 , 35 - 38 reported the association between the level of nestin expression in cancer tissue and OS in patients with DTCs. Pooled results showed that higher expression of nestin (positive) in tumor was associated with worse OS (HR: 1.38, 95% CI: 1.11 to 1.72, P = .004, I 2 = 68%; Figure 2A ) in patients with DTCs. Sensitivity analyses by excluding 1 dataset at a time showed consistent results (HR: 1.30 to 1.47, P all <.05).…”

“…Then, HRs and SEs were logarithmically transformed in order to normalize the distribution and stabilize the variance of the data. 39 The between-study heterogeneity was assessed by the Cochrane’s Q test, and the estimated I 2 statistic. 42 An I 2 >50% reflects a significant heterogeneity.…”

“… 39 The between-study heterogeneity was assessed by the Cochrane’s Q test, and the estimated I 2 statistic. 42 An I 2 >50% reflects a significant heterogeneity. A random-effect model was chosen for the synthesis of the HRs because this model has incorporated the possible influence of between-study heterogeneity, which therefore could retrieve a more generalized result.…”

“…Digestive tract cancers (DTCs) are a group of heterogeneous cancers that mainly include esophagus cancer (EC), gastric cancer (GC), colorectal cancer (CRC), as well as hepatobiliary and pancreatic cancers (PCs). 1 , 2 It has been shown that DTCs remain the important cause of cancer-related death of the global population. 3 - 6 Current treatments for DTCs are comprehensive and complicated, preferably with surgical resection and combined with other strategies such as chemotherapy, radiotherapy, targeted therapy, and immunotherapy.…”

Enhancing therapeutic efficacy in triple‐negative breast cancer and melanoma: synergistic effects of modulated electro‐hyperthermia (mEHT) with NSAIDs especially COX‐2 inhibition in in vivo models

“…Neurexin 3 (NRXN3) encodes a protein involved in synaptic signaling and neural development in the nervous system [ 83 ]. Overlaps between genes involved in neural development and in cancer suggest links between nervous system development and tumorigenesis [ 84 , 85 ]. Emerging research suggests a role of NRXN3 in cancer progression, including breast cancer [ 86 ], through its involvement in cellular adhesion, migration, and invasion.…”