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. 2021 Oct-Dec;62(4):1001-1010.
doi: 10.47162/RJME.62.4.12.

Expression of M3 muscarinic acetylcholine receptors in gastric cancer

Alina Maria Mehedinţeanu  1 , Cecil Sorin Mirea, Puiu Olivian Stovicek, Michael Schenker, Marius Ionuţ Stancu, Ana Maria Ciurea, Liliana Streba, Anca Maria Istrate-Ofiţeru, Teodor Nicuşor Sas, Cristin Constantin Vere
Affiliations

Expression of M3 muscarinic acetylcholine receptors in gastric cancer

Alina Maria Mehedinţeanu et al. Rom J Morphol Embryol. 2021 Oct-Dec.

Abstract

Introduction: Gastric cancer represents a real public health problem as far as incidence, aggressiveness and unfavorable prognosis are concerned. The autonomous nervous system might be one of the major factors involved in the onset, progression, and metastasis, both sympathetically and parasympathetically. The increased activation of the M3 muscarinic acetylcholine receptors (mAChRs) triggers pro-oncogenic mechanisms, especially at a gastric level, through the activation of the Hippo signaling pathway and the increase of the nerve growth factor.

Patients, materials and methods: In this study, biopsy or postoperative gastric resection pieces have been evaluated by histopathological (HP) and immunohistochemical (IHC) examination in a group of 77 gastric patients and 23 patients without an oncological diagnosis. To quantify the IHC signal, also considering the HP aspect, light microscopy images were obtained.

Results: The M3 mAChR expression analysis has been correlated with the different gastric adenocarcinoma differentiation degrees (G1-G3). M3 mAChR presence has been observed also in the non-malignant gastric tissue, but it was significantly increased in the tumor tissue. The highest receptor expression was recorded in patients with a poorly-differentiated (G3) adenocarcinoma, these expressions decreasing with the increase of the differentiation degree towards moderately-differentiated (G2) and well-differentiated (G1).

Conclusions: Surgical or pharmacological parasympathetic activity inhibition could decrease the development and progression of gastric tumors and could improve the gastric cancer patient's prognosis.

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Conflict of interest statement

The authors declare that they have no conflict of interests.

Figures

Figure 1
Figure 1
Histopathological aspects of the biological samples from the patients included in the study: (A) Non-malignant aspect of gastric mucosa; (B) Well-differentiated (G1) gastric adenocarcinoma; (C) Moderately-differentiated (G2) gastric adenocarcinoma; (D) Poorly-differentiated (G3) gastric adenocarcinoma. Hematoxylin–Eosin (HE) staining: (A–D) ×200
Figure 2
Figure 2
Aspects of M3 mAChR immunohistochemical expression depending on the tumor differentiation degree: (A) Non-malignant aspect of gastric mucosa; (B) Well-differentiated (G1) gastric adenocarcinoma; (C) Moderately-differentiated (G2) gastric adenocarcinoma; (D) Poorly-differentiated (G3) gastric adenocarcinoma. Anti-M3 mAChR antibody immunomarking: (A–D) ×200. M3 mAChR: M3 muscarinic acetylcholine receptor
Figure 3
Figure 3
CT images highlighting metastatic lesions in a gastric adenocarcinoma patient: (A) Liver metastatic lesions; (B) Bilateral lung metastatic lesions. CT: Computed tomography
Figure 4
Figure 4
(A–C) CT image of a gastric level tissue lesion, in the pyloric antrum, with a heterogenous structure and iodophilia, with the loss of the left and right hepatic lobe, gallbladder and cephalic pancreas region cleavage space, with perilesional fat infiltration
Figure 5
Figure 5
(A) Gastric adenocarcinoma CT image which highlights parietal tissue thickening, iodophile, at the small gastric curvature level with the interest of the esophageal–gastric junction, before chemotherapy; (B) Gastric adenocarcinoma CT image after chemotherapy (therapeutic response assessment)
Figure 6
Figure 6
Gastric adenocarcinoma macroscopic postoperative piece: (A) Gastric adenocarcinoma macroscopic aspects; (B) UGE gastric adenocarcinoma. UGE: Upper gastrointestinal endoscopy
Figure 7
Figure 7
Mechanisms involved in gastric cancer by overexpression of M3 receptors. Akt: Protein kinase B; EGFR: Epidermal growth factor receptor; ERK: Extracellular signal-regulated kinase; IL: Interleukin; NGF: Nerve growth factor; TAZ: Transcriptional co-activator with PDZ-binding motif; TNFα: Tumor necrosis factor alpha; Wnt: Wingless-Int; YAP: Yes-associated protein
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References

    1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249. - PubMed
    1. Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F, editors. Global Cancer Observatory cancer today. Lyon France: International Agency for Research on Cancer (IARC; 2020. https://gco.iarc.fr/today
    1. Lou L, Wang L, Zhang Y, Chen G, Lin L, Jin X, Huang Y, Chen J. Sex difference in incidence of gastric cancer: an international comparative study based on the Global Burden of Disease Study 2017. BMJ Open. 2020;10(1):e033323–e033323. - PMC - PubMed
    1. Moy KA, Fan Y, Wang R, Gao YT, Yu MC, Yuan JM. Alcohol and tobacco use in relation to gastric cancer: a prospective study of men in Shanghai, China. Cancer Epidemiol Biomarkers Prev. 2010;19(9):2287–2297. - PMC - PubMed
    1. Scherübl H. Alcohol use and gastrointestinal cancer risk. Visc Med. 2020;36(3):175–181. - PMC - PubMed