ArticleCancer cell international2022
CHRNB2 represses pancreatic cancer migration and invasion via inhibiting β-catenin pathway.
Article in Cancer cell international, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 17 citations in OpenAlex.
- Transcriptomic and experimental validation identify biomarkers and regulatory mechanisms associated with the aryl hydrocarbon receptor in nasopharyngeal carcinoma.Translational cancer research · 2026Article
- Effect of TGFβ-ITGB6 feedback loop on liver metastasis in SMAD4 wild-type pancreatic cancer.Chinese medical journal · 2026Article
- Pancreatic cancer EMT‑targeted therapy: Molecular mechanisms and clinical translation (Review).International journal of oncology · 2026Review
- The role of acetylcholine and its receptors in tumor immune regulation: mechanisms and potential therapeutic targets.Molecular cancer · 2025Review
- Cholinergic Receptor Nicotinic Beta 2 Subunit Promotes the Peritoneal Disseminating Metastasis of Colorectal Cancer.Cancers · 2025Article
- Hypoxia- and lactate metabolism-associated prognostic and therapeutic signature in pancreatic cancer.Discover oncology · 2025Article
- Integrative multi-omics analysis reveals the role of toll-like receptor signaling in pancreatic cancer.Scientific reports · 2025Article
- Article
- Construction of a prognostic model with exosome biogenesis- and release-related genes and identification of RAB27B in immune infiltration of pancreatic cancer.Translational cancer research · 2024Article
- Circadian clock-related genome-wide mendelian randomization identifies putatively genes for ulcerative colitis and its comorbidity.BMC genomics · 2024Article
- Machine learning was used to predict risk factors for distant metastasis of pancreatic cancer and prognosis analysis.Journal of cancer research and clinical oncology · 2023Article
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9 authors at 2 institutions in 1 country.
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Abstract
backgroundPancreatic cancer is one of the most lethal disease with highly fatal and aggressive properties. Lymph node ratio (LNR), the ratio of the number of metastatic lymph nodes to the total number of examined lymph nodes, is an important index to assess lymphatic metastasis and predict prognosis, but the molecular mechanism underlying high LNR was unclear.
methodsGene expression and clinical information data of pancreatic cancer were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO). Patients in TCGA were averagely divided into low and high LNR groups. Then, Weighted Gene Co-expression Network Analysis (WGCNA) was utilized to build co-expression network to explore LNR-related modules and hub genes. GO and KEGG analysis was performed to find key pathways related to lymph node metastasis. Next, GSE101448 and the overall survival data in TCGA was employed to further select significant genes from hub genes. Considering the key role of CHRNB2 in LNR and survival, gene set enrichment analysis (GSEA) was applied to find pathways related to CHRNB2 expression in pancreatic cancer. The contribution of CHRNB2 to migrative and invasive ability of pancreatic cancer cells was confirmed by Transwell assays. We finally explored the role of CHRNB2 in EMT and β-catenin pathway via Western Blot.
resultsHigh LNR was significantly related to high T stages and poor prognosis. In WGCNA, 14 hub genes (COL5A1, FN1, THBS2, etc.) were positively related to high LNR, 104 hub genes (FFAR1, SCG5, TMEM63C, etc.) were negatively related to high LNR. After taking the intersection with GSE101448, 13 genes (CDK5R2, SYT7, CACNA2D2, etc.) which might prevent lymph node metastasis were further selected. Among them, CHRNB2 showed the strongest relationship with long survival. Moreover, CHRNB2 also negatively related to the T stages and LNR. Next, knockdown of CHRNB2 expression could acetylcholine (ACh)-independently increase the migration and invasion of pancreatic cancer cells, while CHRNB2 overexpression ACh-independently decrease the migration and invasion of pancreatic cancer cells. For exploring the underlying mechanism, CHRNB2 downregulated β-catenin pathway might through controlling its upstream regulators such as SOX6, SRY, SOX17, and TCF7L2.
conclusionsCHRNB2 negatively relates to lymph node metastasis in pancreatic cancer patients. CHRNB2 could inhibit β-catenin pathway, EMT, migration and invasion of pancreatic cancer cells via ACh-independent mechanism.
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