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| Evaluating Expression and Clinical Value of CALHM2 in Non-small Cell Lung Cancer Through Bioinformatics Data Analysis |
| LIU Jie, HUANG Wei, WANG Lei |
| Changsha Central Hospital, University of South China, Changsha, Hunan, 410004, China |
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Abstract 【Objective】 Based on the high-throughput tumor data in TCGA and GEO, the expression and clinical value of CALHMs family genes such as CALHM2 in non-small cell lung cancer were analyzed. 【Methods】 Using online tools like Oncomine, GEPIA and UALCAN to analyze and verify the expression level of CALHMs (CALHM1-6) family genes in non-small cell lung cancer(NSCLC); Using Human protein Atlas (HPA) to analyze the protein level and location of CALHM2 in NSCLC tissues ; Using GEPIA and UALCAN to analyze the correlations between CALHM2 expression level and pathological stage, lymph node metastasis, p53 mutation and smoking history in patients with NSCLC; Using UALCAN to investigate promoter methylation of CALHM2 in NSCLC; Using Kaplan-Meier Plotter to analyze the relationship between CALHM2 expression level and prognosis of NSCLC including overall survival (OS), first-time progression survival (FP) and post-progression survival (PPS); Using LinkedOmics to analyze the genes that were significantly related to CALHM2 expression in NSCLC; Using Metascape to perform GO function enrichment with CALHM2 correlated genes. 【Results】 The expression of CALHM2 was significantly down-regulated in NSCLC tissue; CALHM2 protein was also significantly reduced in NSCLC tissue. The expression of CALHM2 showed no significant correlation with pathological stage, lymph node metastasis, p53 mutation and smoking history in NSCLC patients. Kaplan-Meier Plotter analysis showed that NSCLC patients with high CALHM2 expression had significantly better OS and FP than those with low CALHM2. LinckedOmics screened a total of 265 genes significantly related to CALHM2, and Metascape enrichment analysis showed that CALHM2 related genes were significantly enriched in lymphocyte activation and migration, immune activation-related processes, and cytokine release regulation. 【Conclusion】 CALHM2 is significantly downregulated in NSCLC and can be used as a prognostic marker for patients with NSCLC.
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Received: 11 January 2021
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[1] Siegel RL,Miller KD,Jemal A.Cancer statistics, 2020[J].CA Cancer J Clin,2020, 70 (1): 7-30.
[2] Bade BC,Dela Cruz CS.Lung cancer 2020: Epidemiology, etiology, and prevention [J].Clin Chest Med,2020, 41 (1): 1-24.
[3] Cao M,Chen W.Epidemiology of lung cancer in China [J].Thorac Cancer,2019, 10 (1): 3-7.
[4] Ma Z,Tanis JE,Taruno A, et al.Calcium homeostasis modulator (calhm) ion channels[J].Pflugers Arch,2016, 468 (3): 395-403.
[5] Roberts-Thomson SJ,Chalmers SB,Monteith GR.The calcium-signaling toolkit in cancer: Remodeling and targeting[J].Cold Spring Harb Perspect Biol,2019, 11 (8): a035204.
[6] Gautier M,Trebak M,Fleig A,et al. Ca2+ homeostasis and cancer [J].Cell Calcium,2019, 84:102084.
[7] O'Reilly D,Buchanan P.Calcium channels and cancer stem cells [J].Cell Calcium,2019, 81:21-28.
[8] Tang Z,Li C,Kang B, et al.Gepia: A web server for cancer and normal gene expression profiling and interactive analyses[J].Nucleic Acids Res,2017, 45 (W1): W98-W102.
[9] Chandrashekar DS,Bashel B,Balasubramanya SAH,et al. Ualcan: A portal for facilitating tumor subgroup gene expression and survival analyses [J].Neoplasia,2017, 19 (8): 649-658.
[10] Nagy A,Lanczky A,Menyhart O,et al. Validation of mirna prognostic power in hepatocellular carcinoma using expression data of independent datasets [J].Sci Rep,2018, 8 (1): 9227.
[11] Vasaikar SV,Straub P,Wang J,et al.Linkedomics: Analyzing multi-omics data within and across 32 cancer types[J].Nucleic Acids Res,2018, 46 (D1): D956-D963.
[12] Zhou Y,Zhou B,Pache L,et al.Metascape provides a biologist-oriented resource for the analysis of systems-level datasets [J].Nat Commun,2019, 10 (1): 1523.
[13] Drozdzyk K,Sawicka M,Bahamonde-Santos MI, et al.Cryo-em structures and functional properties of calhm channels of the human placenta [J].Elife,2020, 9:e55853.
[14] Choi W,Clemente N,Sun W,et al.The structures and gating mechanism of human calcium homeostasis modulator 2 [J].Nature,2019, 576 (7785): 163-167.
[15] Syrjanen JL,Michalski K, Chou, et al.Structure and assembly of calcium homeostasis modulator proteins [J].Nat Struct Mol Biol,2020, 27 (2): 150-159.
[16] Demura K,Kusakizako T,Shihoya W, et al. CryoEM structures of calcium homeostasis modulator channels in diverse oligomeric assemblies [J].Sci Adv,2020, 6 (29): eaba8105.
[17] Cisneros-Mejorado A, Gottlieb M, Ruiz A, et al.Blockade and knock-out of calhm1 channels attenuate ischemic brain damage [J].J Cereb Blood Flow Metab,2018, 38 (6): 1060-1069.
[18] Vingtdeux V,Chang EH,Frattini SA, et al.Calhm1 deficiency impairs cerebral neuron activity and memory flexibility in mice [J].Sci Rep,2016, 6:24250.
[19] Calero O,Bullido MJ,Clarimon J, et al.Genetic variability of the gene cluster calhm 1-3 in sporadic creutzfeldt-jakob disease[J].Prion,2012, 6 (4): 407-412.[20] Malik U.Structural and functional annotation of human fam26f: A multifaceted protein having a critical role in the immune system, [J].Gene,2017, 597:66-75.
[21] Suo A,Childers A,D'Silva A,et al. Cav3.1 overexpression is associated with negative characteristics and prognosis in non-small cell lung cancer[J].Oncotarget,2018, 9 (9): 8573-8583.
[22] Zhou X,Wang W,Zhang S, et al.Cacna1b (cav2.2) overexpression and its association with clinicopathologic characteristics and unfavorable prognosis in non-small cell lung cancer[J].Dis Markers,2017, 2017:6136401.
[23] Zhang Z.Identification of trpcs genetic variants that modify risk for lung cancer based on the pathway and two-stage study, [J].Meta Gene,2016, 9:191-196. |
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2021, Vol. 38 
