| Background:Lung cancer is the most common primary malignant tumor in the lung.The incidence of lung cancer is the first of all tumors,and it is one of the important causes of human cancer death at present[1].The examination of lung cancer mainly depends on imaging examination.The traditional CT diagnosis of lung cancer is usually based on morphology,CT value,enhancement degree and mode,which can not meet the need of clinical differentiation.In addition,the accurate diagnosis of the pathological types of lung cancer has a guiding role in the determination of the treatment regimen.Therefore,we urgently need a non-invasive,accurate and effective method to help diagnose and judge pathological type of lung cancer.The energy spectrum CT also provides many parameters such as single energy imaging,material separation,energy spectrum curve and effective atomic number on the basis of traditional CT[2],which provides a new auxiliary method for better characterization of pulmonary nodules[3].Nevertheless,for the moment,there is no unified opinion at home and abroad on the value of energy spectrum CT in the diagnosis and pathological classification of lung cancer.The purpose of this study is to select the useful and meaningful parameters for the diagnose and judge pathological type of lung cancer by comparing the energy spectrum CT parameters of lung cancer with inflammatory lesions and different pathological types of lung cancer.In addition,some studies have showrn that airway epithelial damage in lurng cancer patients and even some smokers has extended to the nose.There is a certain correlation between the expression of nasal mucosa-related genes and the occurrence of lung cancer.It can be used as a basis for seeking a non-invasive,simple and even diagnostic method for lung cancer,which has a good prospect of application.Hence,it is reasonable to believe that it is feasible to use the gene expression of nasal mucosa as a biomarker for non-invasive screening of lung cancer.Recognition of meaningful lung cancer-related genes from nasal mucosa cells may be a new method for early screening of lung cancerPart I Application of energy spectrum CT parameters in diagnosis and pathological classification of Lung CancerObjective:To explore the value of quantitative parameters of energy spectrum CT on diagnosis the lung cancers and their pathological classification.Methods:110 cases of patients with pulmonary space occupying were examined by CT plain scan and dual phase enhanced scan of chest energy spectrum from March 2017 to January 2019 in Zhongshan Hospital affiliated to Xiamen Universit,including 93 cases of lung cancer and 17 cases of pulmonary inflammation were confirmed by pathology.97 cases with shortest diameter>2cm were divided into 5 groups(including 28 cases of squamous cell carcinoma,41 cases of adenocarcinoma,4 cases of large cell carcinoma,7 cases of small cell carcinoma and 17 cases of inflammatory lesions).The energy spectrum CT quantitative parameters(mainly including IC,NIC,WC,K40-90ke,and Eff-Z)of primary pulmonary lesions in each group were measured.The difference significant in energy spectrum parameters between lung cancer and inflammatory groups and different pathological types of lung cancer was compared,respectively.The diagnostic efficacy of energy spectrum parameters with statistical significance was evaluated by ROC curveResults:1 Comparison of the energy spectrum CT parameters of lung cancer and inflammatory lesions:In plain scan,the values of IC,K40-90ke,v,WC and Eff-Z of lung cancer were(6.49±2.00),(0.91±0.25),(1026.19±8.08),(7.94±0.12),and the corresponding parameters of the Inflammatory lesion were(10.19±5.16),(1.39±0.71),(1015.62±13.46),(8.21±0.31),respectively;The difference was statistically significant(P<0.05).In arterial phase,the values of IC,K40-90kev and NIC of lung cancer were(20.33±5.3 1),(2.78±0.72),(0.1 6±0.04),and the corresponding parameters of the Inflammatory lesion were(23.3 6±5.92),(3.17±0.81),(0.201±0.07),respectively;The difference was statistically significant(P<0.05).In venous phase,the values of IC,K40-90ke,,NIC and WC of lung cancer were(18.76±4.43),(2.54±0.60),(0.45 ±0.10),(1024.93+9.77),and the corresponding parameters of the Inflammatory lesion were(21.79±7.64),(2.96±1.06),(0.53±0.07),(1017.77±7.49),respectively;The difference was statistically significant(P<0.05).ROC curve indicated that the sensitivity and specificity of plain scan WC in the diagnosis of lung cancer were 72.9%and 68.7%,respectively,the area under the curve was 0.745(P<0.05).2.Pairwise comparison of energy spectrum CT parameters of different pathological types of lung cancer:There was significant difference in the values of IC,K40-90kev,WC,Eff-Z in plain scan and IC,K40-90kev,WC in arteria and venous phase and NIC in venous phase between squamous cell carcinoma and adenocarcinoma(P<0.05).The difference of NIC in venous phase between squamous cell carcinoma and small cell carcinoma was statistically significant(P<0.05).As well as the difference of IC,K40-90kev in plain scan and IC,K40-90ke,v,NIC in venous phase between adenocarcinoma and small cell carcinoma was also statistically significant(P<0.05).3.Squamous cell carcinoma and adenocarcinoma as representatives of non-small cell carcinoma.ROC curve indicated that the sensitivity and specificity of venous phase NIC in the diagnosis of non-small cell carcinoma were 85.9%and 100%,respectively,and the area under the curve was 0.913(P<0.05);The sensitivity and specificity of venous phase IC and K40-90k,,in the diagnosis of adenocarcinoma were 83.8%and 86.5%,80.0%and 76.0%,respectively,and the area under the curve were 0.852 and 0.853,respectively(P<0.05).Conclusion:Energy spectrum CT parameters of IC,K40-90kev,WC,Eff-Z in plain scan and IC,K40_gOkev,NIC in arterial phase and IC、K40-90kev、NIC and WC in venous phase can be used to distinguish lung cancer from pulmonary inflammation,in which the plain scan WC value greater than 1021.6 has the highest accuracy in the diagnosis of lung cancer.There all have high efficiency in the diagnosis of non-small cell carcinoma with venous phase NIC greater than 0.375,as well as venous phase IC greater than 17.6 or venous phase K40-90kev greater than 2.355 in the diagnosis of non-small cell carcinoma.Part II Detection and correlation of lung cancer-related genes in nasal mucosaObjective:Comparison of the correlation between quantitative parameters of energy spectrum CT and quantitative detection of genes associated with nasal mucosa lung cancer.Methods:110 cases of patients with pulmonary space occupying were examined by CT plain scan and dual phase enhanced scan of chest energy spectrum from March 2017 to January 2019 in Zhongshan Hospital affiliated to Xiamen Universit.65 cases of nasal mucosa specimens(including 52 cases of lung cancer and 17 cases of pulmonary inflammation were confirmed by pathology)were collected from 97 patients with the shortest diameter>2cm.Moreover,28 cases of nasal mucosa specimens whose have no obvious abnormality on pulmonary CT examination were collected as control group.All cases were divided into 6 groups(including 14 cases of squamous cell carcinoma group,30 cases of adenocarcinoma group,4 cases of small cell carcinoma group,4 cases of large cell carcinoma group,13 cases of inflammatory group and 28 cases of normal control group).qRT-PCR was used to detect the expression of 12 genes(including HCK,NCF1,TLR8?EMR3,CSF2RB,DYSF,SPEF2,ANKFN1,HYDIN,DNAH5,C12orf55 and CCDC113)in nasal mucosa of the patients.The expression quantitative difference of target gene expression in nasal mucosa between squamous cell carcinoma group,adenocarcinoma group,inflammatory group and control group were compared,and the genes related to lung cancer expression were found out.The genes with statistical significance were analyzed by ROC curve to evaluate their diagnostic efficacy in the diagnosis of lung cancer.Finally,the correlation between the quantity of energy spectrum CT parameters and the related genes in nasal epithelial which have statistical significance of squamous cell carcinoma,adenocarcinoma and inflammatory lesions were analyzed.Results:The expression quantity of ANKFN1,TLR8 in squamous cell carcinoma group was higher than that in control group(2.57±0.28,4.02±0.41,respectively),and the expression quantity of CCDC113 in squamous cell carcinoma group was lower than that in control group(0.46±0.03),the difference was statistically significant(p<0.05),The expression quantity of NCF1,TLR8,CSF2RB,DYSF in adenocarcinoma group was higher than that in control group(3.74±0.47,3.22±0.28,24.21±1.12,4.76±1.19,respectively),and the expression quantity of CCDC113 was lower than that in control group(0.50±0.05),the difference was statistically significant(P<0.05).The expression quantity of CCDC113 in the inflammatory group was lower than that in the control group(0.45±0.05),and the difference was statistically significant(P<0.05).ROC curve analysis showed that when the critical value of TLR8 was 1.1597,the sensitivity and specificity of diagnosis of squamous cell carcinoma,exclusion of adenocarcinoma were 75.0%and 95.0%respectively,the area under the curve was 0.744(P<0.05).Quantitative correlation between energy spectrum CT parameters and gene expression in nasal mucosa:1.In squamous cell carcinoma group,there was a negative correlation between plain scan WC and CCDC113(rs=-0.670,P<0.05),that is,with the increase of plain scan WC,the expression level of CCDC113 was decreased.Besides,there also was a negative correlation between WC in venous phase and CCDC113(rs=-0.636,P<0.05),that is,with the increase of WC in venous phase,the expression level of CCDC113 was decreased.2.In adenocarcinoma group,there was a positive correlation between plain scan WC and NCF1(rs=0.459,P<0.05),that is,with the increase of plain scan WC,the expression level of NCF1 was increased.There also was a negative correlation between Eff-Z and NCF1(rs=-0.532,P<0.05),that is,with the increase of Eff-Z,the expression level of NCF1 was decreased.Moreover,there was a positive correlation between WC in arterial phase and CSF2RB(rs=0.560,P<0.05),that is,with the increase of WC in arterial phase,the expression level of CSF2RB was increased.3.There was no significant correlation between energy spectrum CT parameters and nasal mucosa gene in inflammatory group.Conclusion:The up-regulation of the expression of ANKFN1 and TLR8 can be used for screening squamous cell carcinoma,and the up-regulation of the expression of NCF1,TLR8,CSF2RB,DYSF can be used for the screening of adenocarcinomas When the expression quantity of TLR8 was more than 1.1597,it had high efficiency in diagnosing squamous cell carcinoma.NCF1 combined with plain scan WC and Eff-Z of energy spectrum CT had synergetic effect on the diagnosis of adenocarcinomas.The down-regulation of CCDC113 expression combined with WC in plain scan and venous phase of energy spectrum CT is helpful for the diagnosis of squamous cell carcinoma. |
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