Daorong Wang

The nervous system, which regulates organogenesis, homeostasis, and plasticity of the organism during human growth and development, integrates physiological functions of all organ systems, including the immune system. Its extensive network of branches throughout the body reaches the tumor microenvironment (TME), where it secretes neurotransmitters that directly regulate or influence immune cells. This, in turn, indirectly affects the occurrence, development, and metastasis of cancer. Conversely, cancer cells are now understood to secrete neurotrophic factors that remodel the nervous system. Targeting the cross-talk between the nervous system and cancer represents a promising strategy for cancer treatment, some aspects of which have been confirmed in clinical trials. This review addresses gaps in our understanding of the interaction between peripheral nerves and various human cancers. At the intersection of neuroscience and cancer biology, new targets for neuroscience-based cancer therapies are emerging, establishing a significant new pillar in cancer treatment. Graphical abstract

Metastasis, the spread of a tumor or cancer from the primary site of the body to a secondary site, is a multi-step process in cancer progression, accounting for various obstacles in cancer treatment and most cancer-related deaths. Metabolic reprogramming refers to adaptive metabolic changes that occur in cancer cells in the tumor microenvironment (TME) to enhance their survival ability and metastatic potential. Stromal cell metabolism also changes to stimulate tumor proliferation and metastasis. Metabolic adaptations of tumor and non-tumor cells exist not only in the TME but also in the pre-metastatic niche (PMN), a remote TME conducive for tumor metastasis. As a novel mediator in cell-to-cell communication, small extracellular vesicles (sEVs), which have a diameter of 30–150 nm, reprogram metabolism in stromal and cancer cells within the TME by transferring bioactive substances including proteins, mRNAs and miRNAs (microRNAs). sEVs can be delivered from the primary TME to PMN, affecting PMN formation in stroma rewriting, angiogenesis, immunological suppression and matrix cell metabolism by mediating metabolic reprogramming. Herein, we review the functions of sEVs in cancer cells and the TME, how sEVs facilitate PMN establishment to trigger metastasis via metabolic reprogramming, and the prospective applications of sEVs in tumor diagnosis and treatment.

Background: The most common subtype of colorectal cancer is colon adenocarcinoma (COAD). However, few studies have investigated the predictive value of N7-methylguanosine(m7G)-related long-noncoding RNAs (lncRNAs) in COAD. We aim to use m7G-related lncRNAs to construct a prognostic model for COAD.Methods: RNA-seq data and the corresponding clinical and prognostic Data were downloaded from The Cancer Genome Atlas (TCGA) database.M7G-related lncRNAs with prognostic values were identified using the univariate and multivariate Cox regression. Based on Kaplan-Meier curves, we compared the survival rates in the high-risk and low-risk groups. The functional enrichment of m7G-related lncRNAs with a prognostic value was interpreted using gene set enrichment analysis (GSEA). Finally, we studied the relationship between predictive signature and treatment response in patients with COAD.Results: Six m7G-related lncRNAs (LINC01063, ARRDC1-AS1, AL354993.2, ZEB1-AS1, SNHG16, LINC02474) were identified to establish a signature. The m7G-related lncRNA signature may be able to predict COAD patients' prognosis independently. The OS times of patients in the high-risk group were shorter than those in the low-risk group. With an area under the receiver operating characteristic curve of 0.742, the m7G-related lncRNA prognostic signature had a better prognostic prediction than clinicopathological variables. The high-risk group has the most tumor-related pathways, according to GSEA. The prognostic characteristic was linked to the immunological state of COAD patients, according to GSEA. The conventional chemotherapy medicines axitinib, cytarabine, sorafenib, parthenolide and vorinostat were more sensitive in high-risk individuals.Conclusion: Our study develops a COAD risk model consisting of six lncRNAs related to m7G that have independent prognostic values. Clinically, the lncRNA signature could improve prediction of outcomes for patients with COAD and, with further prospective validation, could help guide tailored therapy for COAD patients

Background: This study aimed to evaluate the effect of perioperative transcutaneous electrical acupoint stimulation (TEAS) on postoperative cognitive dysfunction (POCD) in older patients who were diagnosed with gastrointestinal tumor and received radical resection of gastrointestinal tumors under general anesthesia. Methods: A total of 68 patients who received radical resection of gastrointestinal tumors under general anesthesia were randomly divided into two groups. TEAS group patients received TEAS treatment. The treatment time was 30 min before the induction of anesthesia until the end of the surgery, 1 day before operation and from the first day to the third day after the operation. Except on the day of surgery, we treated the patients for 30 min once a day. In the sham TEAS group, the electronic stimulation was not applied and the treatment was the same as the TEAS group. The primary outcome was perioperative cognition evaluated by the Mini-Mental State Examination (MMSE) and secondary outcomes were the perioperative level of interleukin-6 (IL-6), S100 calcium-binding protein β (S100β), and C-reactive protein (CRP). Results: The postoperative score of MMSE, orientation, memory, and short-term recall in the sham TEAS group was significantly lower than the preoperative and TEAS group (P < 0.05). The incidence of POCD in the TEAS group (21.88%) was lower than those in the sham TEAS group (40.63%). S100β, IL-6, and CRP in the TEAS group were significantly lower than those in the sham TEAS group on the third day after the operation (P< 0.05). Postoperative S100β, IL-6, and CRP in two groups were significantly higher than those before operation except for S100β on the third day after the operation in the TEAS group (P < 0.05). Conclusions: Perioperative TEAS treatment reduced the postoperative inflammatory response and increased the postoperative cognitive function score and decrease the incidence of POCD in geriatric patients with gastrointestinal tumor. Trial registration: ClinicalTrials.gov NCT04606888. Registered on 27 October 2020. https://register.clinicaltrials.gov.

Introduction: N6-methyladenosine (m6A) is the most abundant form of methylation modification in eukaryotic cell mRNA. However, the role of m6A in gastric cancer is unclear, which is one of the most common gastrointestinal malignancies. The m6A-relevant mRNA signatures and risk scores are determined to predict the prognosis of gastric cancer in this study.Methods: The expression profiles and clinical information of 367 patients were downloaded from the Cancer Genome. Cluster analysis and univariate Cox analysis were used to identify the regulatory factors of RNA methylation associated with gastric cancer prognosis. The co-expression network was constructed by the WGCNA package in R. Then, the correlations between module eigengenes and clinical traits were calculated to identify the relevant modules. We used univariate Cox analysis to screen for genes that were significantly associated with prognosis in the module (P < 0.01 was considered significant). We identified hub genes by LASSO and multivariate analysis, and developed a Cox prognostic model. Finally, the hub gene expression values weighted by the coefficients from the LASSO regression generated a risk score for each patient, receiver operating characteristic (ROC) and Kaplan-Meier curves were used to assess the prognostic capacity of the risk scores.Results: HNRNPC was shown as P1 in the TCGA gastric cancer data set, which might be a pathogenic factor affecting the prognosis of gastric cancer. The results indicated that AARD, ASPN, SLAMF9, MIR3117 and DUSP1 were hub genes affecting the prognosis of gastric cancer patients, and the m6A methylation of these mRNAs might be regulated by HNRNPC. The risk score = − (0.166195281×AARD + 0.016850602×ASPN + 0.591607997×SLAMF9 + 0.591607997×MIR3117 + 0.00276337×DUSP1), and our results indicated a bad performance of the five-gene signature for survival prediction (P < 0.05).Conclusion: HNRNPC (a m6A RNA methylation regulator) can participate in the serious progression of gastric cancer by regulating the m6A of AARD, ASPN, SLAMF9, MIR3117 and DUSP1, which may be used for prognosis stratification and treatment strategy formulation.