The Study Of TM4SF19 Expression And Prognosis In Lung Squamous Carcinoma Based On Bioinformatics

Background:Lung Cancer is a common malignant tumor globally for the last several decades.NSCLC(non-small cell lung carcinoma)is a the main histologic classification representing more than 80%to 85%of lung cancers of which 25%to 30%are LUSC(lung squamous cell carcinoma).The therapies for patients with LUSC are radiotherapy,chemotherapy,targeted therapy,immunotherapy and surgery.Though progress in prevention,diagnosis and treatment of lung cancer,the five-year survival rate of lung cancer remains 19%.TM4SF19 is a member of Transmembrane 4 L six family,which play a role inregulating cell differentiation,migration,proliferation,tumor progression,and chemoresistance.TM4SF19/OCTM4 and five members of TM4SF have been reported with similar topology and sequence homology,including TM4SF1/L6-Ag,TM4SF4/IL-TMP,TM4SF5/L6H,TM4SF18/L6D,and TM4SF20/TCCE518,and the six members involve in cell migration and invasion.Lnc RNA TM4SF19-AS1 is observed upregulated in LSCC and LUSC,and its expression is correlated with TM4SF19.However,little is known about the role of TM4SF19 in the progression of LUSC.Methods:Firstly,we used online bioinformatics analysis tools to predict the expression of TM4SF19 in a variety of tumors,especially in LUSC.We also analyzed the relationship between TM4SF19 expression and LUSC clinical parameters.And then we predicted the interacting functions of related genes based on bioinformatics analysis tools,and analysed the biological process,celluar componengt,molecular function and KEGG pathway of the genes.Moreover,the relationship between TM4SF19 expression and tumor microenvironment,and also immune cell infiltration was evaluated using Estimate and ss GSEA algorithms,respectively.Finally,we validated the expression of TM4SF19 in the serum of LUSC patients with ELISA kit.Results:The expression of TM4SF19 was higher in various cancers,especially LUSC,than that in tissues adjacent to tumor based on bioinformatics analysis.Through the analysis of the TCGA datasets,the TM4SF19 expression is higher in LUSC(P<0.001),and TM4SF19 expression was significantly associated with T stage(P=0.01)and primary therapy outcome(P=0.03).ss GSEA predicted that TM4SF19 was mainly involved in keratinization、keratinocyte differentiation、epidermal cell differentiation、cornified envelope、intermediate filament、keratin filament、structural constituent of skin epidermis、interleukin-1 recetor binding、serine-type endopeptidase activity,Neuroactive ligand-receptor interaction and cytokine-cytokine receptor interaction。By the ESTIMATE algorithm,we found that the immune scores(P=0.0376)were significantly reduced in the group of high expression of TM4SF19,the expression of TM4SF19 was negatively correlated with the proportion of a DC(r=-0.197,P<0.0001)、B cells(r=-0.185,P<0.0001)、CD8~+T cells(r=-0.172,P=0.0001)、cytotoxic cells(r=-0.169,P=0.0001)、mast cells(r=-0.120,P=0.0071)、NK cells(r=-0.120,P=0.0073)、T cells(r=-0.179,P<0.0001)、T helper cells(r=-0.196,P<0.0001)、TFH(r=-0.260,P<0.0001)以及Th2 cells(r=-0.147,P=0.0009),and positively correlated with the proportion of Tcm(r=0.141,P=0.0015).Finally we validated expression of TM4SF19 in the serum of LUSC patients with ELISA kit,TM4SF19 was overexpressed in LUSC than that in LUAD and control(P<0.05).Conclusions:Expression of TM4SF19 is higher in LUCS based on TCGA datasets,and upregulation of TM4SF19 is correlated with LUSC T stage and primary therapy outcome.TM4SF19 mainly involves in keratinization,intermediate filament and cytokine-cytokine receptor interaction,which relate to the progression of a variety of cancers.TM4SF19 plays an important role in tumor microenvironment,and the expression of TM4SF19 is upregulated in the serum of LUSC patients.