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. 2022 Dec 2;14(23):5969. doi: 10.3390/cancers14235969

Figure 5.

Figure 5

Graphical synopsis of the role of SNPs in prognosis of cholangiocarcinoma. Various SNPs are associated with clinical prognosis of CCA. EGFR rs2017000 affects EGFR expression and thus the EGFR signaling pathway (tumor cell proliferation, angiogenesis, tumor invasion, metastasis and inhibition of apoptosis). RNF43 rs2257205 inhibits the Wnt signaling pathway, while EZH2 rs887569 inhibits the Wnt signaling and EGFR/JAK/STAT signaling pathway. G proteins are activated upon binding to ligands, initiating different signaling pathways and leading to various biological effects. CXCR1 rs2234671 (encodes the IL8 receptor), GNAS rs7121 (encodes an activated G protein alpha subunit) and GNB3 rs5443 (encodes the β3 subunit of the G protein) are associated with G protein-coupled receptor-mediated signaling pathways. As an important transcription factor, NRF2 (encoded by NFE2L2) regulates antioxidant, cytoprotective, and metabolic enzymes and is involved in drug resistance as well as cancer cell proliferation. SNPs in DNA repair genes can naturally be associated with cancer prognosis (RFC1 rs1051266; XRCC1 rs25487; ERCC2 rs13181). RFC1 is also associated with the replication of DNA. GALNT14 enzymes are associated with the O-glycosylation of proteins. GALNT14 rs9617162 affects the activity of GALNT14. AC, adenylate cyclase; AKT, Protein kinase B; APC, adenomatous polyposis coli protein; cAMP, Cyclic adenosine monophosphate; CCA, cholangiocarcinoma; CXCR1, C-X-C motif chemokine receptor 1; ERK, extracellular signal-regulated kinase; EGFR, epithelial growth factor receptor; ERCC1, ERCC excision repair 1; GALNT14, polypeptide N-acetylgalactosaminyltransferase 14; GNB3, G protein subunit beta 3; GPCR, G protein-coupled receptor; GSK3β, glycogen synthase kinase 3β; IKK, I-kappa-B-kinase; JAK, The Janus kinase; mTOR, mammalian target of rapamycin; PKA, protein kinase A; MEK, Mitogen-activated protein kinase; 5-MTHF, 5-methyl THF; NFAT, Nuclear factor of activated T cells; NFE2L2, NFE2 like bZIP transcription factor 2; NF-κB, Nuclear factor kappa-light-chain-enhancer of activated B cells; NRF2, Nuclear factor erythroid 2-related factor 2; PKA, Protein kinase A; PKC, Protein kinase C; PIP2, phosphatidylinositol(4, 5)bisphosphate; PI3K, Phosphoinositide 3-kinase; PLC-β, phospholipase C beta; RAF, serine/threonine-specific protein kinases; Rap1, Ras-proximate-1; RAS, family of genes involving cellular signal transduction; RhoA, Ras homolog family member A; RNF43, Ring finger protein 43; SRF, serum response factor; STAT3, signal transducer and activator of transcription 3.