| Objective:To investigate the expression of Dickkopf-1(DKK1)in lung adenocarcinoma tissues and its relationship with tumor epithelial-mesenchymal transition(EMT),as well as the relationship between the two and the clinicopathological features of patients.Methods:(1)The expression of DKK1 in 41 lung adenocarcinoma tissues and 12 adjacent lung tissues was detected by real-time quantitative polymerase chain reaction(RT-q PCR)and immunohistochemical staining(IHC),and the correlation between DKK1 m RNA expression and its protein expression and the relationship between DKK1 m RNA expression and clinicopathological parameters(age,gender,tumor size,tumor differentiation degree,lymph node metastasis and clinical stage)were analyzed.(2)Immunohistochemical staining was used to detect DKK1 and EMT-related proteins(E-cadherin、Vimentin)in 157 cases of lung adenocarcinoma tissues and 60 cases of adjacent lung tissues,further verifying the relationship between DKK1 protein and clinicopathological parameters(age,gender,size,tumor differentiation degree,pleural invasion,lymph node metastasis,M stage and clinical stage),and analyzing its relationship with EMT type and prognosis of patients.Result:(1)In 41 cases of lung cancer tissues and 12 cases of adjacent lung tissues,the expression levels of DKK1 m RNA and its protein were positively correlated,and the expression of DKK1 m RNA and its protein in lung adenocarcinoma tissues was lower than that in adjacent lung tissues,with statistically significant difference(P<0.05).The expression of DKK1 m RNA in poorly differentiated tumors(median 0.349)was lower than that in highly-moderately differentiated tumors(median 0.679),and the difference was statistically significant(P<0.05).The expression of DKK1 m RNA in tumors with lymph node metastasis(median 0.268)was lower than that in tumors without lymph node metastasis(median 0.621),and the difference was statistically significant(P<0.05).The expression of DKK1 m RNA in clinical stage III patients(median 0.268)was lower than that in clinical stage I + II patients(median 0.762),and the difference was statistically significant(P<0.05).DKK1 m RNA expression was not related to sex,age and tumor size(P>0.05).(2)In 157 cases of lung adenocarcinoma,98 cases had low expression of DKK1(DKK1-L)and 59 cases had high expression of DKK1(DKK1-H).The DKK1-L ratio of tumors with maximum diameter >5cm(100%,7/7)was higher than that of tumors with maximum diameter ≤ 3cm(58.1%,72/124),and the difference was statistically significant(P<0.05).The DKK1-L ratio of poorly differentiated tumors(84.7%,50/59)was higher than that of highly-moderately differentiated tumors(49.0%,48/98),and the difference was statistically significant(P<0.05).The proportion of tumor DKK1-L with lymph node metastasis(74.1%,40/54)was higher than that without lymph node metastasis(56.3%,58/103),and the difference was statistically significant(P<0.05).The proportion of DKK1-L in M1 group(83.9%,26/31)was higher than that in M0 group(57.1%,72/126),and the difference was statistically significant(P<0.05).The proportion of DKK1-L in stage III + IV group(80.4%,41/51)was higher than that in stage I + II group(53.8%,57/106),and the difference was statistically significant(P<0.05).The expression of DKK1 protein was not related to the patient’s sex,age,tumor pleural invasion(P>0.05).(3)157 cases of lung adenocarcinoma tissues,including 50 cases of EMT epithelial type,63 cases of intermediate type and 44 cases of mesenchymal type.The proportion of DKK-L decreased sequentially in interstitial,intermediate and epithelial types,which were 84.1%(37/44),58.7%(37/63)and 48.0%(24/50)respectively,with statistically significant difference(P<0.05).High,medium and low differentiated adenocarcinoma in the EMT interstitial type proportion reduced,in turn were 72.7%(32/44),25%(11/44)and 2.3%(1/44);Poorly differentiated adenocarcinoma accounted for the highest in the EMT interstitial and second intermediate type,minimum epithelial type,the difference was statistically significant(P < 0.05).(4)The 5-year PFS in DKK1-L group(58.7%)was significantly lower than that in DKK1-H group(86.3%),and the difference was statistically significant(P<0.05).The5-year OS in DKK1-L group(64.2%)was lower than that in DKK1-H group(92.9%),and the difference was statistically significant(P<0.05).The 5-year PFS of EMT mesenchymal type(52.3%)was lower than that of epithelial type(82.0%)and intermediate type(68.8%),and the difference was statistically significant(P<0.05).The 5-year OS of EMT mesenchymal type(58.1%)was lower than that of epithelial type(87.8%)and intermediate type(74.6%),and the difference was statistically significant(P<0.05).(5)Univariate analysis showed that DKK1 protein expression,EMT typing,tumor differentiation degree,M stage and clinical stage were correlated with PFS and OS(P<0.05).Age,T stage and N stage were correlated with PFS(P<0.05),but not with OS(P>0.05).Multivariate survival analysis showed that DKK1 protein expression and M stage in lung adenocarcinoma tissues were independent influencing factors of PFS and OS for5 years(P<0.05).Conclusion:(1)The expression of DKK1 in lung adenocarcinoma tissues is lower than that in adjacent lung tissues,suggesting that DKK1 may play a tumor suppressor role in lung adenocarcinoma.(2)Low expression of DKK1 in lung adenocarcinoma tissue is related to low tumor differentiation,lymph node metastasis,distant metastasis,high clinical stage and EMT mesenchymal type,it is suggested that low expression of DKK1 may promote tumor metastasis by promoting the transformation of tumor cells into EMT mesenchymal type.(3)Low expression of DKK1 in lung adenocarcinoma tissue is a risk factor for tumor recurrence or metastasis in patients with lung adenocarcinoma,and may be used as an independent predictor for evaluating the prognosis of patients. |
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