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This study assessed calcitonin receptor (CALCR) expression and its prognostic value across LIHC and other cancers using TCGA and MSigDB data, plus cluster-based fibrosis stratification and single-sample gene set enrichment.",{"@graph":14,"@context":73},[15,34,56],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & 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was the purpose of evaluating CALCR in liver cancer?","Question",{"text":63,"@type":64},"To determine how CALCR expression relates to prognosis and to clarify its involvement in pathways connecting fibrosis, ferroptosis, and cancer progression, including immune-response implications.","Answer",{"name":66,"@type":61,"acceptedAnswer":67},"How were fibrosis and ferroptosis levels quantified in LIHC patients?",{"text":68,"@type":64},"Fibrosis-related gene expression was used to classify patients into two clusters via ConsensusClusterPlus, and ssGSEA quantified fibrosis and ferroptosis levels.",{"name":70,"@type":61,"acceptedAnswer":71},"What was the clinical significance of CALCR expression in LIHC?",{"text":72,"@type":64},"High CALCR expression was associated with shortened overall survival and disease-specific survival, and CALCR functioned as a significant prognostic 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Implications for the immunotherapy response  \nSIJIA WANG 1 , WEI WANG2 and JIA ZENG 1  \n1  \nDepartment of Health Management, The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410001, 2  \nP.R. China; Graduate School, Hunan University of Traditional Chinese Medicine, Changsha, Hunan 410001, P.R. China  \nReceived July 30, 2024; Accepted November 1, 2024  \nDOI: 10. 3892/mmr.2024.13406  \nAbstract. Liver hepatocellular carcinoma (LIHC) is a prevalent and lethal malignancy with a complex molecular landscape. Fibrosis and ferroptosis are implicated in LIHC progression, yet their roles remain to be elucidated. The present study investigated the expression and prognostic significance of calcitonin receptor (CALCR), a gene that intersects the pathways of fibrosis and ferroptosis, across LIHC and other types of cancer. Data were obtained from The Cancer Genome Atlas and the Molecular Signatures Database. LIHC patients were classified into two clusters based on fibrosis‑related gene expression using ConsensusClusterPlus. Single‑sample gene set enrichment analysis was employed to quantify fibrosis and ferroptosis levels. Correlation, survival and nomogram anal‑ yses were performed to assess the prognostic value of CALCR. Additionally, single‑cell RNA sequencing data from the  \nCorrespondence to: Professor Jia Zeng, Department of Health Management, The First Hospital of Hunan University of Chinese Medicine, 95 Shaoshan Middle Road, Changsha, Hunan 410001, P.R. China  \nE‑mail: [13548671301@163.com](13548671301@163.com)  \nAbbreviations: LIHC, liver hepatocellular carcinoma; TISCH2, Tumor Immune Single Cell Hub 2; TCGA, The Cancer Genome Atlas; MSigDB, Molecular Signatures Database; ssGSEA, single‑sample gene set enrichment analysis; OS, overall survival; DSS, disease‑specific survival; CALCR, calcitonin receptor; GTEx, Genotype‑Tissue Expression; UMAP, uniform manifold approximation and projection; tSNE, t‑distributed stochastic neighbor embedding; GO, Gene Ontology; DFI, disease‑free interval; PFI, progression‑free interval; KM, Kaplan‑Meier; TMB, tumor mutational burden; MSI, microsatellite instability; NEO, neoantigen load; HRD, homologous recombination deficiency; CNV, copy number variation; GEO, Gene Expression Omnibus; HPA, Human Protein Atlas; TIDE, tumor immune dysfunction and exclusion; FBS, fetal bovine serum; siRNA, small interfering RNA; CCK‑8, cell counting kit‑8; FITC, fluorescein isothiocyanate; PI, propidium iodide  \nKey words: liver hepatocellular carcinoma, calcitonin receptor, fibrosis, ferroptosis, genomic heterogeneity  \nTumor Immune Single Cell Hub 2 (TISCH2) and pan‑cancer analyses of genomic heterogeneity features were incorporated. The present study also identified a putative regulatory role for CALCR in LIHC cell migration, proliferation and apoptosis. CALCR was identified as a significant prognostic marker for LIHC. Patients with high CALCR expression exhibited shortened overall survival (OS) and disease‑specific survival (DSS) . Specifically, the hazard ratios (HRs) for OS and DSS were 1.76 [95% confidence interval (CI): 1. 23=2 .49) and 1.77 (95% CI: 1.13=2.78], respectively, with corresponding P‑values of 0.002 for OS and 0.013 for DSS. Analyses of immune cell infiltration revealed a more complex immune environment inpatients with low CALCR expression, suggesting differential responses to immunotherapy. Furthermore, in HepG‑2 and HuH‑7 cells, small interfering (si)‑CALCR increased apoptosis while reducing proliferation and migration compared with si‑negative control. CALCR serves as a significant prognostic biomarker for LIHC, influencing both molecular pathways and the immune landscape. Its expression is associated with improved survival outcomes and distinct genomic features, positioning it as a potential therapeutic target and predictor of immunotherapy efficacy.  \nIntroduction  \nLiver hepatocellular ca","cbCailyDn66ta9Ni","https://ap.wps.com/l/cbCailyDn66ta9Ni","pdf",13133592,15,"English","# Abstract\n# Introduction\n## Liver hepatocellular carcinoma and clinical challenge\n## Role of fibrosis in hepatocarcinogenesis\n## Ferroptosis in cancer biology","[{\"question\":\"What was the purpose of evaluating CALCR in liver cancer?\",\"answer\":\"To determine how CALCR expression relates to prognosis and to clarify its involvement in pathways connecting fibrosis, ferroptosis, and cancer progression, including immune-response implications.\"},{\"question\":\"How were fibrosis and ferroptosis levels quantified in LIHC patients?\",\"answer\":\"Fibrosis-related gene expression was used to classify patients into two clusters via ConsensusClusterPlus, and ssGSEA quantified fibrosis and ferroptosis levels.\"},{\"question\":\"What was the clinical significance of CALCR expression in LIHC?\",\"answer\":\"High CALCR expression was associated with shortened overall survival and disease-specific survival, and CALCR functioned as a significant prognostic biomarker.\"}]","Role of CALCR expression in liver cancer - Implications for the immunotherapy response | PDF",1789999736,38]